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Conserved domains on  [gi|2462595283|ref|XP_054205071|]
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adhesion G protein-coupled receptor A3 isoform X4 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
 674-981 0e+00

seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.


The actual alignment was detected with superfamily member cd15999:

Pssm-ID: 475119  Cd Length: 312  Bit Score: 574.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  674 ASLLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYS 753
Cdd:cd15999      1 ADLLHPVVYATAVVLLLCLLTIIVSYIYHHSLVRISRKSWHMLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  754 TLATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 833
Cdd:cd15999     81 TLATVLWVGVTARNIYKQVTRKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  834 SLGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAANENGEINHQDS----MSLSLISTSALENEHT 909
Cdd:cd15999    161 SLGAFYGPAGFIIFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAASEHGELNHQDSgsssASCSLVSTSALENEHS 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462595283  910 FHSQLLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWIMTCCP 981
Cdd:cd15999    241 FQAQLLGASLALFLYVALWIFGALAVSLYYPMDLVFSCLFGATCLSLGAFLVVHHCVNREDVRRAWIATCCP 312
LRR_8 pfam13855
Leucine rich repeat;
5-59 9.10e-17

Leucine rich repeat;


:

Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 75.64  E-value: 9.10e-17
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462595283    5 ILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRI 59
Cdd:pfam13855    7 DLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
LRR_8 pfam13855
Leucine rich repeat;
47-100 5.03e-12

Leucine rich repeat;


:

Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 62.16  E-value: 5.03e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2462595283   47 SSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSSLSQGTFDYLASLRSL 100
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYL 54
PCC super family cl28216
polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) ...
 53-154 6.12e-09

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.


The actual alignment was detected with superfamily member TIGR00864:

Pssm-ID: 188093 [Multi-domain]  Cd Length: 2740  Bit Score: 60.87  E-value: 6.12e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283   53 DLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSslsqgtfdylaslrslefqteyllCDCNILWMHRWVKEKNITVRD--- 129
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFE------------------------CDCGLARLPRWAEEKGVKVRQpea 56

                           90       100
                   ....*....|....*....|....*
gi 2462595283  130 TRCVYPKSLQAQPVTGVKQELLTCD 154
Cdd:TIGR00864   57 ALCAGPGALAGQPLLGIPLLDSGCD 81
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 622-661 5.29e-06

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.


:

Pssm-ID: 460350  Cd Length: 44  Bit Score: 44.61  E-value: 5.29e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2462595283  622 WDFDLlNGQGGWKSDGCHILYSDENITTIQCYSLSNYAVL 661
Cdd:pfam01825    6 WDFTN-STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 281-334 7.96e-05

Hormone receptor domain; This extracellular domain contains four conserved cysteines that probably for disulphide bridges. The domain is found in a variety of hormone receptors. It may be a ligand binding domain.


:

Pssm-ID: 397086  Cd Length: 64  Bit Score: 41.59  E-value: 7.96e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  281 WPRTLAGITAYLQCTRNTHGSgiypgnpQDERKAWRRCDRGGFWAD---DDYSRCQY 334
Cdd:pfam02793   14 WPRTPAGETVEVPCPDYFSGF-------DPRGNASRNCTEDGTWSEhppSNYSNCTS 63
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 167-259 3.74e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


:

Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 37.87  E-value: 3.74e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283   167 SHRQVVFEGDSLPFQCMASYiDQDMQVLWYQDGriVETDESQGIFVEKNMIHNCSLiasalTISNIQAGSTGNWGCHVQT 246
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASG-SPPPEVTWYKQG--GKLLAESGRFSVSRSGSTSTL-----TISNVTPEDSGTYTCAATN 72

                            90
                    ....*....|...
gi 2462595283   247 KRGNNTRTVDIVV 259
Cdd:smart00410   73 SSGSASSGTTLTV 85
 
Name Accession Description Interval E-value
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
 674-981 0e+00

G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR125 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, which also includes orphan receptors GPR123 and GPR124. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320665  Cd Length: 312  Bit Score: 574.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  674 ASLLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYS 753
Cdd:cd15999      1 ADLLHPVVYATAVVLLLCLLTIIVSYIYHHSLVRISRKSWHMLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  754 TLATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 833
Cdd:cd15999     81 TLATVLWVGVTARNIYKQVTRKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  834 SLGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAANENGEINHQDS----MSLSLISTSALENEHT 909
Cdd:cd15999    161 SLGAFYGPAGFIIFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAASEHGELNHQDSgsssASCSLVSTSALENEHS 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462595283  910 FHSQLLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWIMTCCP 981
Cdd:cd15999    241 FQAQLLGASLALFLYVALWIFGALAVSLYYPMDLVFSCLFGATCLSLGAFLVVHHCVNREDVRRAWIATCCP 312
LRR_8 pfam13855
Leucine rich repeat;
5-59 9.10e-17

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 75.64  E-value: 9.10e-17
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462595283    5 ILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRI 59
Cdd:pfam13855    7 DLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
6-101 4.77e-16

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 81.90  E-value: 4.77e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELKNgSFSGLSLLERLDLRNNLISSIdPGAFWGLSSLKRLDLTNNRIGCLNADIFrGLTNLVRLNLSGNLFSS 85
Cdd:COG4886    143 LSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPEPLG-NLTNLEELDLSGNQLTD 219

                           90
                   ....*....|....*.
gi 2462595283   86 LSQGtfdyLASLRSLE 101
Cdd:COG4886    220 LPEP----LANLTNLE 231
LRR_8 pfam13855
Leucine rich repeat;
47-100 5.03e-12

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 62.16  E-value: 5.03e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2462595283   47 SSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSSLSQGTFDYLASLRSL 100
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYL 54
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 714-961 2.48e-11

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 65.38  E-value: 2.48e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  714 HMlvNLCFHIFLTCVVFVGGITQTRNASI--------CQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEP 785
Cdd:pfam00002   40 HL--NLFASFILRALLFLVGDAVLFNKQDldhcswvgCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVE---------VF 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  786 PPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWE-PSLGAFYGPASFITFVNCMYFLSIFIQLKRHp 864
Cdd:pfam00002  109 FSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYG---EDDGCWLSNEnGLWWIIRGPILLIILVNFIIFINIVRILVQK- 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  865 erkyeLKEPTEEQQRLAanengeinhqdSMSLSLISTSALenehtfhsqllgasltlllyVAL----WMFGALAVSLYYP 940
Cdd:pfam00002  185 -----LRETNMGKSDLK-----------QYRRLAKSTLLL--------------------LPLlgitWVFGLFAFNPENT 228

                          250       260
                   ....*....|....*....|.
gi 2462595283  941 LDLVFSFVFGATSlSFSAFFV 961
Cdd:pfam00002  229 LRVVFLYLFLILN-SFQGFFV 248
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 6-101 3.07e-11

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 64.42  E-value: 3.07e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELKNgsFSGLSLLERLDLRNNLISSI---------------------------DPGAFWGLS-SLKRLDLTNN 57
Cdd:cd21340     53 LQNNQIEKIEN--LENLVNLKKLYLGGNRISVVeglenltnleelhienqrlppgekltfDPRSLAALSnSLRVLNISGN 130

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2462595283   58 RIGCLNAdiFRGLTNLVRLNLSGNLFSSLSQgTFDYLASLRSLE 101
Cdd:cd21340    131 NIDSLEP--LAPLRNLEQLDASNNQISDLEE-LLDLLSSWPSLR 171
PCC TIGR00864
polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) ...
 53-154 6.12e-09

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.


Pssm-ID: 188093 [Multi-domain]  Cd Length: 2740  Bit Score: 60.87  E-value: 6.12e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283   53 DLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSslsqgtfdylaslrslefqteyllCDCNILWMHRWVKEKNITVRD--- 129
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFE------------------------CDCGLARLPRWAEEKGVKVRQpea 56

                           90       100
                   ....*....|....*....|....*
gi 2462595283  130 TRCVYPKSLQAQPVTGVKQELLTCD 154
Cdd:TIGR00864   57 ALCAGPGALAGQPLLGIPLLDSGCD 81
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 622-661 5.29e-06

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.


Pssm-ID: 460350  Cd Length: 44  Bit Score: 44.61  E-value: 5.29e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2462595283  622 WDFDLlNGQGGWKSDGCHILYSDENITTIQCYSLSNYAVL 661
Cdd:pfam01825    6 WDFTN-STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 621-664 2.49e-05

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.


Pssm-ID: 197639  Cd Length: 49  Bit Score: 42.76  E-value: 2.49e-05
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 2462595283   621 RWDFDllngQGGWKSDGCHILYSDENITTIQCYSLSNYAVLMDL 664
Cdd:smart00303    7 FWDES----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDV 46
LRRCT smart00082
Leucine rich repeat C-terminal domain;
107-141 7.64e-05

Leucine rich repeat C-terminal domain;


Pssm-ID: 214507 [Multi-domain]  Cd Length: 51  Bit Score: 41.26  E-value: 7.64e-05
                            10        20        30
                    ....*....|....*....|....*....|....*..
gi 2462595283   107 LLCDCNILWMHRWVKEKNITVR--DTRCVYPKSLQAQ 141
Cdd:smart00082    3 FICDCELRWLLRWLQANEHLQDpvDLRCASPSSLRGP 39
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 281-334 7.96e-05

Hormone receptor domain; This extracellular domain contains four conserved cysteines that probably for disulphide bridges. The domain is found in a variety of hormone receptors. It may be a ligand binding domain.


Pssm-ID: 397086  Cd Length: 64  Bit Score: 41.59  E-value: 7.96e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  281 WPRTLAGITAYLQCTRNTHGSgiypgnpQDERKAWRRCDRGGFWAD---DDYSRCQY 334
Cdd:pfam02793   14 WPRTPAGETVEVPCPDYFSGF-------DPRGNASRNCTEDGTWSEhppSNYSNCTS 63
LRR_RI cd00116
Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 ...
 6-115 1.71e-04

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).


Pssm-ID: 238064 [Multi-domain]  Cd Length: 319  Bit Score: 45.04  E-value: 1.71e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISElKNGS-----FSGLSLLERLDLRNNLISS-----IDPGAFWGLSSLKRLDLTNNRIGCLNA-DIFRGLTN-- 72
Cdd:cd00116    200 LNNNGLTD-EGASalaetLASLKSLEVLNLGDNNLTDagaaaLASALLSPNISLLTLSLSCNDITDDGAkDLAEVLAEke 278

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2462595283   73 -LVRLNLSGNLFSSLSQgtfdYLASLRSLEFQteyllCDCNILW 115
Cdd:cd00116    279 sLLELDLRGNKFGEEGA----QLLAESLLEPG-----NELESLW 313
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 6-84 3.10e-04

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 45.22  E-value: 3.10e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKIS-ELKNgsFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFS 84
Cdd:PLN00113   459 LARNKFFgGLPD--SFGSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLS 536
HormR smart00008
Domain present in hormone receptors;
281-334 5.76e-04

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 39.42  E-value: 5.76e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462595283   281 WPRTLAGITAYLQCTRNThgSGIYPGNpqderKAWRRCDRGGFWA--DDDYSRCQY 334
Cdd:smart00008   15 WPQTPAGQLVEVPCPKYF--SGFSYKT-----GASRNCTENGGWSppFPNYSNCTS 63
LRR smart00370
Leucine-rich repeats, outliers;
22-45 3.68e-03

Leucine-rich repeats, outliers;


Pssm-ID: 197688 [Multi-domain]  Cd Length: 24  Bit Score: 35.79  E-value: 3.68e-03
                            10        20
                    ....*....|....*....|....
gi 2462595283    22 LSLLERLDLRNNLISSIDPGAFWG 45
Cdd:smart00370    1 LPNLRELDLSNNQLSSLPPGAFQG 24
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 167-259 3.74e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 37.87  E-value: 3.74e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283   167 SHRQVVFEGDSLPFQCMASYiDQDMQVLWYQDGriVETDESQGIFVEKNMIHNCSLiasalTISNIQAGSTGNWGCHVQT 246
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASG-SPPPEVTWYKQG--GKLLAESGRFSVSRSGSTSTL-----TISNVTPEDSGTYTCAATN 72

                            90
                    ....*....|...
gi 2462595283   247 KRGNNTRTVDIVV 259
Cdd:smart00410   73 SSGSASSGTTLTV 85
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 160-244 4.66e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 37.16  E-value: 4.66e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  160 PSFYMTPSHrQVVFEGDSLPFQCMASYIDQDmQVLWYQDGRIVETDESQGIFVEKNMihncsliaSALTISNIQAGSTGN 239
Cdd:pfam13927    2 PVITVSPSS-VTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRSRSLSGSN--------STLTISNVTRSDAGT 71


                   ....*
gi 2462595283  240 WGCHV 244
Cdd:pfam13927   72 YTCVA 76
 
Name Accession Description Interval E-value
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
 674-981 0e+00

G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR125 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, which also includes orphan receptors GPR123 and GPR124. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320665  Cd Length: 312  Bit Score: 574.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  674 ASLLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYS 753
Cdd:cd15999      1 ADLLHPVVYATAVVLLLCLLTIIVSYIYHHSLVRISRKSWHMLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  754 TLATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 833
Cdd:cd15999     81 TLATVLWVGVTARNIYKQVTRKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  834 SLGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAANENGEINHQDS----MSLSLISTSALENEHT 909
Cdd:cd15999    161 SLGAFYGPAGFIIFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAASEHGELNHQDSgsssASCSLVSTSALENEHS 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462595283  910 FHSQLLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWIMTCCP 981
Cdd:cd15999    241 FQAQLLGASLALFLYVALWIFGALAVSLYYPMDLVFSCLFGATCLSLGAFLVVHHCVNREDVRRAWIATCCP 312
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
 674-979 7.61e-113

orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group III adhesion GPCRs include orphan GPR123, GPR124, GPR125, and their closely related proteins. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 also interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Furthermore, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. GPR125 directly interacts with dishevelled (Dvl) via its intracellular C-terminus, and together, GPR125 and Dvl recruit a subset of planar cell polarity (PCP) components into membrane subdomains, a prerequisite for activation of Wnt/PCP signaling. Thus, GPR125 influences the noncanonical WNT/PCP pathway, which does not involve beta-catenin, through interacting with and modulating the distribution of Dvl.


Pssm-ID: 320387 [Multi-domain]  Cd Length: 260  Bit Score: 353.22  E-value: 7.61e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  674 ASLLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYS 753
Cdd:cd15259      1 FELLHPVVYAGAALCLLCLLATIITYIVFHRLIRISRKGRHMLVNLCLHLLLTCVVFVGGINRTANQLVCQAVGILLHYS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  754 TLATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSrpnAPYCWMAWEP 833
Cdd:cd15259     81 TLCTLLWVGVTARNMYKQVTKTAKPPQDEDQPPRPPKPMLRFYLIGWGIPLIICGITAAVNLDNYST---YDYCWLAWDP 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  834 SLGAFYGPASFITFVNCMYFLSIFIQLKRHPERkyelkepteeqqrlaanengeinhqdsmslslistsalenehtFHSQ 913
Cdd:cd15259    158 SLGAFYGPAALIVLVNCIYFLRIYCQLKGAPVS-------------------------------------------FQSQ 194

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462595283  914 LLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWIMTC 979
Cdd:cd15259    195 LRGAVITLFLYVAMWACGALAVSQRYFLDLVFSCLYGATCSSLGLFVLIHHCLSREDVRQSWRQCC 260
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
 676-981 1.46e-109

G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR123 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, and also includes orphan receptors GPR124 and GPR125. GPR123 is predominantly expressed in the CNS including thalamus, brain stem and regions containing large pyramidal cells, yet its biological function remains to be determined. Adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320666 [Multi-domain]  Cd Length: 275  Bit Score: 345.01  E-value: 1.46e-109
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  676 LLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTL 755
Cdd:cd16000      3 FLHPVVYACTAVMLLCLFASIITYIVHHSTIRISRKGWHMLLNFCFHTALTFAVFAGGINRTKYPIICQAVGIVLHYSTL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  756 ATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSR-PNAPYCWMAWEPS 834
Cdd:cd16000     83 STMLWIGVTARNIYKQVTKKPHLCQDTDQPPYPKQPLLRFYLVSGGVPFIICGITAATNINNYGTEdEDTPYCWMAWEPS 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  835 LGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKepteeqqrlaanengeinhqdsmslslistsaleNEHTFHSQL 914
Cdd:cd16000    163 LGAFYGPVAFIVLVTCIYFLCTYVQLRRHPERKYELK----------------------------------NEHSFKAQL 208

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  915 LGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWiMTCCP 981
Cdd:cd16000    209 RAAAFTLFLFTATWAFGALAVSQGHFLDMIFSCLYGAFCVTLGLFILIHHCAKRDDVWHCW-WSCCP 274
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
 677-981 5.82e-82

G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR124 is an orphan receptor that has been classified as that belongs to the group III of adhesion GPCRs, which also includes orphan GPR123 and GPR125. GPR124, also known as tumor endothelial marker 5 (TEM5), is highly expressed in tumor vessels and in the vasculature of the developing embryo. GPR124 is essentially required for proper angiogenic sprouting into neural tissue, CNS-specific vascularization, and formation of the blood-brain barrier. GPR124 interacts with the PDZ domain of DLG1 (discs large homolog 1) through its PDZ-binding motif. Recently, studies of double-knockout mice showed that GPR124 functions as a co-activator of Wnt7a/Wnt7b-dependent beta-catenin signaling in brain endothelium. Moreover, WNT7-stimulated beta-catenin signaling is regulated by GPR124's intracellular PDZ binding motif and leucine-rich repeats (LRR) in its N-terminal extracellular domain. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320664 [Multi-domain]  Cd Length: 268  Bit Score: 269.13  E-value: 5.82e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  677 LHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLA 756
Cdd:cd15998      4 LHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHYSSLS 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  757 TVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYgsRPNAPYCWMAWEPSLG 836
Cdd:cd15998     84 TLLWMGVKARVLHKELTWRAPPPQEGDPALPTPRPMLRFYLIAGGIPLIICGITAAVNIHNY--RDHSPYCWLVWRPSLG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  837 AFYGPASFITFVNCMYFLSIFIQLKRHPErkyelkepteeqqrlaanengeinHQDSMSLSLISTSALENEHTFhsqllg 916
Cdd:cd15998    162 AFYIPVALILLVTWIYFLCAGLHLRGPSA------------------------DGDSVYSPGVQLGALVTTHFL------ 211

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462595283  917 asltlllYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWiMTCCP 981
Cdd:cd15998    212 -------YLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASW-RACCP 268
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
 709-975 2.67e-41

adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G protein-coupled receptors; The B2 subfamily of class B GPCRs consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320168 [Multi-domain]  Cd Length: 253  Bit Score: 152.73  E-value: 2.67e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  709 SLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKRcqdpdeppPP 788
Cdd:cd15040     34 KRKPTKILLNLCLALLLANLLFLFGINSTDNPVLCTAVAALLHYFLLASFMWMLVEALLLYLRLVKVFGT--------YP 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  789 PRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNapYCWMAWE-PSLGAFYGPASFITFVNCMYFLSIFIQLKRHP-ER 866
Cdd:cd15040    106 RHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSG--YCWLSNGnGLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSaKR 183

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  867 KYELKEPTEEQQRLAAnengeinhqdSMSLSLISTsalenehtfhsqllgasltlllyvalWMFGALAVSlyyPLDLVFS 946
Cdd:cd15040    184 NKKKRKKTKAQLRAAV----------SLFFLLGLT--------------------------WIFGILAIF---GARVVFQ 224

                          250       260       270
                   ....*....|....*....|....*....|
gi 2462595283  947 FVFGATSlSFSAFFV-VHHCVNREDVRLAW 975
Cdd:cd15040    225 YLFAIFN-SLQGFFIfIFHCLRNKEVRKAW 253
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
 699-975 9.03e-30

class B family of seven-transmembrane G protein-coupled receptors; The class B of seven-transmembrane GPCRs is classified into three major subfamilies: subfamily B1 (secretin-like receptor family), B2 (adhesion family), and B3 (Methuselah-like family). The class B receptors have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi or prokaryotes. The B1 subfamily comprises receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the subfamily B1 receptors preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The subfamily B2 consists of cell-adhesion receptors with 33 members in humans and vertebrates. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing a variety of structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, linked to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Furthermore, the subfamily B3 includes Methuselah (Mth) protein, which was originally identified in Drosophila as a GPCR affecting stress resistance and aging, and its closely related proteins.


Pssm-ID: 410627 [Multi-domain]  Cd Length: 260  Bit Score: 119.62  E-value: 9.03e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  699 YIYHHSLIRISlksWHMLVNLCFHIFLTCVVFVGGITQTRNAS--ICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKa 776
Cdd:cd13952     26 YLLFPKLRNLR---GKILINLCLSLLLAQLLFLIGQLLTSSDRpvLCKALAILLHYFLLASFFWMLVEAFDLYRTFVKV- 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  777 krcqdpdEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNA--PYCWM-AWEPSLGAFYGPASFITFVNCMYF 853
Cdd:cd13952    102 -------FGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYggEYCWLsNGNALLWAFYGPVLLILLVNLVFF 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  854 LSIFIQLKRHPERKYELKEPTEEQQRLAAnengeinhqdsmSLSLIstsalenehtfhsqllgasltlllyVAL---WMF 930
Cdd:cd13952    175 ILTVRILLRKLRETPKQSERKSDRKQLRA------------YLKLF-------------------------PLMgltWIF 217

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 2462595283  931 GALAVslYYPLDLVFSFVFGATSlSFSAFFV-VHHCVNREDVRLAW 975
Cdd:cd13952    218 GILAP--FVGGSLVFWYLFDILN-SLQGFFIfLIFCLKNKEVRRLL 260
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
 714-980 4.85e-22

cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuron migration and axon guidance in the CNS.


Pssm-ID: 320557 [Multi-domain]  Cd Length: 254  Bit Score: 96.94  E-value: 4.85e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  714 HMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVT--KKAKRCQdpdeppppprp 791
Cdd:cd15441     38 SIHKNLVACLLLAELLFLLGINQTENLFPCKLIAILLHYFYLSAFSWLLVESLHLYRMLTepRDINHGH----------- 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  792 MLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWM-AWEPSLGAFYGPASFITFVNCMYF---LSIFIQLKRHPERK 867
Cdd:cd15441    107 MRFYYLLGYGIPAIIVGLSVGLRPDGYG---NPDFCWLsVNETLIWSFAGPIAFVIVITLIIFilaLRASCTLKRHVLEK 183

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  868 YELKepteeqQRLAANengeinhqdSMSLSLISTSalenehtfhsqllgasltlllyvalWMFGALAVSlyYPLDlVFSF 947
Cdd:cd15441    184 ASVR------TDLRSS---------FLLLPLLGAT-------------------------WVFGLLAVN--EDSE-LLHY 220

                          250       260       270
                   ....*....|....*....|....*....|...
gi 2462595283  948 VFGATSLSFSAFFVVHHCVNREDVRLAWIMTCC 980
Cdd:cd15441    221 LFAGLNFLQGLFIFLFYCIFNKKVRRELKNALL 253
LRR_8 pfam13855
Leucine rich repeat;
5-59 9.10e-17

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 75.64  E-value: 9.10e-17
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 2462595283    5 ILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRI 59
Cdd:pfam13855    7 DLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
 718-872 1.06e-16

invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors; This subgroup includes latrophilin-like proteins that are found in invertebrates such as insects and worms. Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of vertebrate latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320556 [Multi-domain]  Cd Length: 259  Bit Score: 81.54  E-value: 1.06e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYK---QVTKKAKRcqdpdeppppprPMLR 794
Cdd:cd15440     42 NLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFLAAFSWMLLEGFQLYVmlvEVFEPEKS------------RIKW 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  795 FYLIGGGIPIIVCGITAAANIKNYGSRpnaPYCWMAWE-PSLGAFYGPASFITFVNCMyFLSIFIQLK-RHPERKYELKE 872
Cdd:cd15440    110 YYLFGYGLPALIVAVSAGVDPTGYGTE---DHCWLSTEnGFIWSFVGPVIVVLLANLV-FLGMAIYVMcRHSSRSASKKD 185
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
 714-975 1.82e-16

orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group V adhesion GPCRs include orphan receptors GPR133, GPR144, and closely related proteins. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the G(s) protein, leading to activation of adenylate cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320599 [Multi-domain]  Cd Length: 252  Bit Score: 80.45  E-value: 1.82e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  714 HMlvNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdePPPPPRPML 793
Cdd:cd15933     40 HK--NLCVALLLAQILLLAGEWAEGNKVACKVVAILLHFFFMAAFSWMLVEGLHLYLMIVK----------VFNYKSKMR 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  794 RFYLIGGGIPIIVCGITAAANIKNYGSrPNapYCWMA------WepslgAFYGPASFITFVNCMYF---LSIFIQLKRHP 864
Cdd:cd15933    108 YYYFIGWGLPAIIVAISLAILFDDYGS-PN--VCWLSlddgliW-----AFVGPVIFIITVNTVILilvVKITVSLSTND 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  865 ErkyelKEPTEEQQRLAANENGEInhqdsMSLSLISTSalenehtfhsqllgasltlllyvalWMFGALAVSlyyPLDLV 944
Cdd:cd15933    180 A-----KKSQGTLAQIKSTAKASV-----VLLPILGLT-------------------------WLFGVLVVN---SQTIV 221

                          250       260       270
                   ....*....|....*....|....*....|.
gi 2462595283  945 FSFVFGATSLSFSAFFVVHHCVNREDVRLAW 975
Cdd:cd15933    222 FQYIFVILNSLQGLMIFLFHCVLNSEVRSAF 252
LRR_8 pfam13855
Leucine rich repeat;
25-83 2.30e-16

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 74.48  E-value: 2.30e-16
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462595283   25 LERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLF 83
Cdd:pfam13855    3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
6-101 4.77e-16

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 81.90  E-value: 4.77e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELKNgSFSGLSLLERLDLRNNLISSIdPGAFWGLSSLKRLDLTNNRIGCLNADIFrGLTNLVRLNLSGNLFSS 85
Cdd:COG4886    143 LSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPEPLG-NLTNLEELDLSGNQLTD 219

                           90
                   ....*....|....*.
gi 2462595283   86 LSQGtfdyLASLRSLE 101
Cdd:COG4886    220 LPEP----LANLTNLE 231
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
 706-972 5.40e-15

Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320657 [Multi-domain]  Cd Length: 254  Bit Score: 76.42  E-value: 5.40e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  706 IRISLKSWHMlvNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEP 785
Cdd:cd15991     32 LRSNLHSIHK--NLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMSTFAWMFVEGLHIYRMLTE---------VR 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  786 PPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWEPSL-GAFYGPASFITFVNCMYFLsifiqlkrhp 864
Cdd:cd15991    101 NINTGHMRFYYVVGWGIPAIITGLAVGLDPQGYG---NPDFCWLSVQDTLiWSFAGPIGIVVIINTVIFV---------- 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  865 erkYELKEPTEEQQRlaanengeiNHQDSMSLSLISTSALenehtfhsqllgaslTLLLYVALWMFGALAVSlyyPLDLV 944
Cdd:cd15991    168 ---LAAKASCGRRQR---------YFEKSGVISMLRTAFL---------------LLLLISATWLLGLMAVN---SDTLS 217

                          250       260
                   ....*....|....*....|....*...
gi 2462595283  945 FSFVFGATSLSFSAFFVVHHCVNREDVR 972
Cdd:cd15991    218 FHYLFAIFSCLQGIFIFFFHCIFNKEVR 245
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
5-103 1.45e-14

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 77.28  E-value: 1.45e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    5 ILSNNKISELKNgSFSGLSLLERLDLRNNLISSIdPGAFWGLSSLKRLDLTNNRIGCLnaDIFRGLTNLVRLNLSGNLFS 84
Cdd:COG4886    188 DLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLTDL--PELGNLTNLEELDLSNNQLT 263

                           90
                   ....*....|....*....
gi 2462595283   85 SLSQGTFdyLASLRSLEFQ 103
Cdd:COG4886    264 DLPPLAN--LTNLKTLDLS 280
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 719-854 1.58e-14

CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the leukocyte cell-surface antigen CD97 and the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4), are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily B2 of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying numbers of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of CD97, alternative splicing results in three isoforms possessing either three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. For example, CD97, which is involved in angiogenesis and the migration and invasion of tumor cells, has been shown to promote cell aggregation in a GPS proteolysis-dependent manner. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320554 [Multi-domain]  Cd Length: 261  Bit Score: 75.18  E-value: 1.58e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  719 LCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTkkakrcQDPDEPPPPPRPMLrfyLI 798
Cdd:cd15438     43 LCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLAAFCWMSLEGVELYLMVV------QVFNTQSLKKRYLL---LI 113

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  799 GGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWEPS-LGAFYGPASFITFVNCMYFL 854
Cdd:cd15438    114 GYGVPLVIVAISAAVNSKGYG---TQRHCWLSLERGfLWSFLGPVCLIILVNAIIFV 167
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
 700-880 1.11e-12

Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G protein-coupled receptors; The subfamily B3 of class B GPCRs consists of Methuselah (Mth) and its closely related proteins found in bilateria. Mth was originally identified in Drosophila as a GPCR affecting stress resistance and aging. In addition to the seven transmembrane helices, Mth contains an N-terminal extracellular domain involved in ligand binding, and a third intracellular loop (IC3) required for the specificity of G-protein coupling. Drosophila Mth mutants showed an increase in average lifespan by 35% and greater resistance to a variety of stress factors, including starvation, high temperature, and paraquat-induced oxidative toxicity. Moreover, mutations in two endogenous peptide ligands of Methuselah, Stunted A and B, showed an increased in lifespan and resistance to oxidative stress induced by dietary paraquat. These results strongly suggest that the Stunted-Methuselah system plays important roles in stress response and aging.


Pssm-ID: 410632 [Multi-domain]  Cd Length: 270  Bit Score: 69.56  E-value: 1.11e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  700 IYHHSLIRiSLKSWH--MLVNLCFHIFLTCVVFV-GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKA 776
Cdd:cd15039     23 LAVYALLP-ELRNLHgkCLMCLVLSLFVAYLLLLiGQLLSSGDSTLCVALGILLHFFFLAAFFWLNVMSFDIWRTFRGKR 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  777 KRCQDPDEPPPpprpmLRFY-LIGGGIPIIVCGITAAANIKN--YGSRPN--APYCWM--AWePSLGAFYGPASFITFVN 849
Cdd:cd15039    102 SSSSRSKERKR-----FLRYsLYAWGVPLLLVAVTIIVDFSPntDSLRPGygEGSCWIsnPW-ALLLYFYGPVALLLLFN 175

                          170       180       190
                   ....*....|....*....|....*....|..
gi 2462595283  850 CMYFLSIFIQLKRHP-ERKYELKEPTEEQQRL 880
Cdd:cd15039    176 IILFILTAIRIRKVKkETAKVQSRLRSDKQRF 207
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
 699-977 1.50e-12

orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Group VIII adhesion GPCRs include orphan GPCRs such as GPR56, GPR64, GPR97, GPR112, GPR114, and GPR126. GPR56 is involved in the regulation of oligodendrocyte development and myelination in the central nervous system via coupling to G(12/13) proteins, which leads to the activation of RhoA GTPase. GPR126, on the other hand, is required for Schwann cells, but not oligodendrocyte myelination in the peripheral nervous system. Gpr64 is mainly expressed in the epididymis of male reproductive tract, and targeted deletion of GPR64 causes sperm stasis and efferent duct blockage due to abnormal fluid reabsorption, resulting in male infertility. GPR64 is also over-expressed in Ewing's sarcoma (ES), as well as upregulated in other carcinomas from kidney, prostate or lung, and promotes invasiveness and metastasis in ES via the upregulation of placental growth factor (PGF) and matrix metalloproteinase (MMP) 1. GPR97 is identified as a lymphatic adhesion receptor that is specifically expressed in lymphatic endothelium, but not in blood vascular endothelium, and is shown to regulate migration of lymphatic endothelial cells via the small GTPases RhoA and cdc42. GPR112 is specifically expressed in normal enterochromatin cells and gastrointestinal neuroendocrine carcinoma cells, but its biological function is unknown. GPR114 is mainly found in granulocytes (polymorphonuclear leukocytes), and GPR114-transfected cells induced an increase in cAMP levels via coupling to G(s) protein. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320386 [Multi-domain]  Cd Length: 267  Bit Score: 69.37  E-value: 1.50e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  699 YIYHHSLIRISLKSWHMlvNLCFHIFLTCVVFV--GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKka 776
Cdd:cd15258     26 YIAFRKLRRDYPSKIHM--NLCAALLLLNLAFLlsSWIASFGSDGLCIAVAVALHYFLLACLTWMGLEAFHLYLLLVK-- 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  777 krcqdpDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYG-----SRPNAPYCWMAWEPSLGAFY----GPASFITF 847
Cdd:cd15258    102 ------VFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGpitipNGEGFQNDSFCWIRDPVVFYitvvGYFGLTFL 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  848 VNCMYFLSIFIQLKRHPERKyELKEPTEEQQRLaanengeinhqdsmsLSLISTSALenehtfhsqllgasltlllyvaL 927
Cdd:cd15258    176 FNMVMLATVLVQICRLREKA-QATPRKRALHDL---------------LTLLGLTFL----------------------L 217

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 2462595283  928 WMFGALAVSLYYPLDLVFSFVFgATSLSFSAFFV-VHHCVNREDVRLAWIM 977
Cdd:cd15258    218 GLTWGLAFFAWGPFNLPFLYLF-AIFNSLQGFFIfIWYCSMKENVRKQWRA 267
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
16-100 1.58e-12

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 71.12  E-value: 1.58e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283   16 NGSFSGLSLLERLDLRNNLISSIdPGAFWGLSSLKRLDLTNNRIGCLNADIFrGLTNLVRLNLSGNLFSSLSQGtFDYLA 95
Cdd:COG4886    106 NEELSNLTNLESLDLSGNQLTDL-PEELANLTNLKELDLSNNQLTDLPEPLG-NLTNLKSLDLSNNQLTDLPEE-LGNLT 182


                   ....*
gi 2462595283   96 SLRSL 100
Cdd:COG4886    183 NLKEL 187
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
6-108 1.76e-12

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 70.73  E-value: 1.76e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELkNGSFSGLSLLERLDLRNNLISSIDpgAFWGLSSLKRLDLTNNRIGCLNADIfrGLTNLVRLNLSGNLFSS 85
Cdd:COG4886    212 LSGNQLTDL-PEPLANLTNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLTD 286

                           90       100
                   ....*....|....*....|...
gi 2462595283   86 LSQGTFDYLASLRSLEFQTEYLL 108
Cdd:COG4886    287 LKLKELELLLGLNSLLLLLLLLN 309
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
 715-863 2.37e-12

epidermal growth factor-like module-containing mucin-like hormone receptors, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4) and the leukocyte cell-surface antigen CD97, are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying number of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of EMR2, alternative splicing results in four isoforms possessing either two (EGF1,2), three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320555 [Multi-domain]  Cd Length: 263  Bit Score: 68.52  E-value: 2.37e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  715 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVtkkakRCQDPDEPPPPPRPMLR 794
Cdd:cd15439     39 LHLQLSLCLFLADLLFLVGIDRTDNKVLCSIIAGFLHYLFLACFAWMFLEAVHLFLTV-----RNLKVVNYFSSHRFKKR 113

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2462595283  795 F-YLIGGGIPIIVCGITAAANIKNYGSRpnaPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 863
Cdd:cd15439    114 FmYPVGYGLPAVIVAISAAVNPQGYGTP---KHCWLSMEKGfIWSFLGPVCVIIVINLVLFCLTLWILREK 181
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
 715-860 2.86e-12

brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediate direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320379  Cd Length: 253  Bit Score: 68.05  E-value: 2.86e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  715 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKrcqdpdepppPPRPMLR 794
Cdd:cd15251     40 ILINFCLSIISSNILILVGQTQTLNKGVCTMTAAFLHFFFLSSFCWVLTEAWQSYMAVTGRMR----------TRLIRKR 109

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462595283  795 FYLIGGGIPIIVCGITAA-ANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQL 860
Cdd:cd15251    110 FLCLGWGLPALVVAVSVGfTRTKGYGT---SSYCWLSLEGGlLYAFVGPAAAVVLVNMVIGILVFNKL 174
LRR_8 pfam13855
Leucine rich repeat;
47-100 5.03e-12

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 62.16  E-value: 5.03e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 2462595283   47 SSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSSLSQGTFDYLASLRSL 100
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYL 54
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
 704-975 1.44e-11

orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR133 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR144. The function of GPR144 has not yet been characterized, whereas GPR133 is highly expressed in the pituitary gland and is coupled to the Gs protein, leading to activation of adenylyl cyclase pathway. Moreover, genetic variations in the GPR133 have been reported to be associated with adult height and heart rate. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 66.10  E-value: 1.44e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  704 SLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpd 783
Cdd:cd15256     31 SVSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLPCKIMAILLHFFFLSAFAWMLVEGLHLYSMVIK--------- 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  784 EPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNapyCWMAWEP-SLGAFYGPASFITFVNcmyfLSIFIQLKR 862
Cdd:cd15256    102 VFGSEESKHFYYYGIGWGSPLLICIISLTSALDSYGESDN---CWLSLENgAIWAFVAPALFVIVVN----IGILIAVTR 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  863 HPERkyelkepteeqqrlAANENGEInHQDSMSLSLISTSALENEHTFHSQllgasltlllyvalWMFGALAVSLYyplD 942
Cdd:cd15256    175 VISR--------------ISADNYKV-HGDANAFKLTAKAVAVLLPILGSS--------------WVFGVLAVNTH---A 222

                          250       260       270
                   ....*....|....*....|....*....|....
gi 2462595283  943 LVFSFVFgATSLSFSAFFV-VHHCVNREDVRLAW 975
Cdd:cd15256    223 LVFQYMF-AIFNSLQGFFIfLFHCLLNSEVRAAF 255
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
 718-979 1.78e-11

Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. Celsr3 is expressed in both the developing and adult mouse brain. It has been functionally implicated in proper neuronal migration and axon guidance in the CNS. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320659 [Multi-domain]  Cd Length: 254  Bit Score: 66.02  E-value: 1.78e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 797
Cdd:cd15993     42 NIAAALFLSELLFLLGINRTENQFLCTVVAILLHYFFLSTFAWLFVQGLHIYRMQTE---------ARNVNFGAMRFYYA 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  798 IGGGIPIIVCGITAAANIKNYGsrpNAPYCWMA-WEPSLGAFYGPASFITFVNCMYFLsIFIQLKRHPERKYELKEPTEE 876
Cdd:cd15993    113 IGWGVPAIITGLAVGLDPEGYG---NPDFCWISiHDKLVWSFAGPIVVVIVMNGVMFL-LVARMSCSPGQKETKKTSVLM 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  877 QQRlaanengeinhqDSMSLSLISTsalenehtfhsqllgasltlllyvALWMFGALAVSLYYpldLVFSFVF-GATSLS 955
Cdd:cd15993    189 TLR------------SSFLLLLLIS------------------------ATWLFGLLAVNNSV---LAFHYLHaILCCLQ 229

                          250       260
                   ....*....|....*....|....
gi 2462595283  956 FSAFFVVhHCVNREDVRLAWIMTC 979
Cdd:cd15993    230 GLAVLLL-FCVLNEEVQEAWKLAC 252
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
 718-863 2.15e-11

Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; member of the class B2 family of seven-transmembrane G protein-coupled receptors; ETL (EGF-TM7-latrophilin-related protein) belongs to Group I adhesion GPCRs, which also include latrophilins (also called lectomedins or latrotoxin receptors). All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. ETL, for instance, contains EGF-like repeats, which also present in other EGF-TM7 adhesion GPCRs, such as Cadherin EGF LAG seven-pass G-type receptors (CELSR1-3), EGF-like module receptors (EMR1-3), CD97, and Flamingo. ETL is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320553 [Multi-domain]  Cd Length: 258  Bit Score: 65.67  E-value: 2.15e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTkkakrcqdpDEPPPPPRPMLRFYL 797
Cdd:cd15437     42 NLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLAAFAWMCIEGIHLYLIVV---------GVIYNKGFLHKNFYI 112

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  798 IGGGIPIIVCGITAAANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 863
Cdd:cd15437    113 FGYGSPAVVVGISAALGYKYYGT---TKVCWLSTENNfIWSFIGPACLIILVNLLAFGVIIYKVFRH 176
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 714-961 2.48e-11

7 transmembrane receptor (Secretin family); This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GCPRs). They have been described in many animal species, but not in plants, fungi or prokaryotes. Three distinct sub-families are recognized. Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways. Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin, and brain-specific angiogenesis inhibitors amongst others. Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteriztic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.


Pssm-ID: 459625 [Multi-domain]  Cd Length: 248  Bit Score: 65.38  E-value: 2.48e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  714 HMlvNLCFHIFLTCVVFVGGITQTRNASI--------CQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEP 785
Cdd:pfam00002   40 HL--NLFASFILRALLFLVGDAVLFNKQDldhcswvgCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVE---------VF 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  786 PPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWE-PSLGAFYGPASFITFVNCMYFLSIFIQLKRHp 864
Cdd:pfam00002  109 FSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYG---EDDGCWLSNEnGLWWIIRGPILLIILVNFIIFINIVRILVQK- 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  865 erkyeLKEPTEEQQRLAanengeinhqdSMSLSLISTSALenehtfhsqllgasltlllyVAL----WMFGALAVSLYYP 940
Cdd:pfam00002  185 -----LRETNMGKSDLK-----------QYRRLAKSTLLL--------------------LPLlgitWVFGLFAFNPENT 228

                          250       260
                   ....*....|....*....|.
gi 2462595283  941 LDLVFSFVFGATSlSFSAFFV 961
Cdd:pfam00002  229 LRVVFLYLFLILN-SFQGFFV 248
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 6-101 3.07e-11

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 64.42  E-value: 3.07e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELKNgsFSGLSLLERLDLRNNLISSI---------------------------DPGAFWGLS-SLKRLDLTNN 57
Cdd:cd21340     53 LQNNQIEKIEN--LENLVNLKKLYLGGNRISVVeglenltnleelhienqrlppgekltfDPRSLAALSnSLRVLNISGN 130

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2462595283   58 RIGCLNAdiFRGLTNLVRLNLSGNLFSSLSQgTFDYLASLRSLE 101
Cdd:cd21340    131 NIDSLEP--LAPLRNLEQLDASNNQISDLEE-LLDLLSSWPSLR 171
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
 717-853 3.36e-11

EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; group II adhesion GPCRs, including the leukocyte cell-surface antigen CD97 and the epidermal growth factor (EGF)-module-containing, mucin-like hormone receptor (EMR1-4), are primarily expressed in cells of the immune system. All EGF-TM7 receptors, which belong to the B2 subfamily B2 of adhesion GPCRs, are members of group II, except for ETL (EGF-TM7-latrophilin related protein), which is classified into group I. Members of the EGF-TM7 receptors are characterized by the presence of varying numbers of N-terminal EGF-like domains, which play critical roles in ligand recognition and cell adhesion, linked by a stalk region to a class B seven-transmembrane domain. In the case of CD97, alternative splicing results in three isoforms possessing either three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. On the other hand, EMR2 generates four isoforms possessing either two (EGF1,2), three (EGF1,2,5), four (EGF1,2,3,5) or five (EGF1,2,3,4,5) EGF-like domains. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. For example, CD97, which is involved in angiogenesis and the migration and invasion of tumor cells, has been shown to promote cell aggregation in a GPS proteolysis-dependent manner. CD97 is widely expressed on lymphocytes, monocytes, macrophages, dendritic cells, granulocytes and smooth muscle cells as well as in a variety of human tumors including colorectal, gastric, esophageal pancreatic, and thyroid carcinoma. EMR2 shares strong sequence homology with CD97, differing by only six amino acids. However, unlike CD97, EMR2 is not found in those of CD97-positive tumor cells and is not expressed on lymphocytes but instead on monocytes, macrophages and granulocytes. CD97 has three known ligands: CD55, decay-accelerating factor for regulation of complement system; chondroitin sulfate, a glycosaminoglycan found in the extracellular matrix; and the integrin alpha5beta1, which play a role in angiogenesis. Although EMR2 does not effectively interact with CD55, the fourth EGF-like domain of this receptor binds to chondroitin sulfate to mediate cell attachment.


Pssm-ID: 320597 [Multi-domain]  Cd Length: 262  Bit Score: 65.23  E-value: 3.36e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  717 VNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVtkkaKRCQDPDEPPPPPRPMLRFY 796
Cdd:cd15931     41 LHLCLCLSMSHTLFLAGIEYVENELACTVMAGLLHYLFLASFVWMLLEALQLHLLV----RRLTKVQVIQRDGLPRPLLC 116

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462595283  797 LIGGGIPIIVCGITAAANIKNYGsRPNapYCWMAWEPS-LGAFYGPASFITFVNCMYF 853
Cdd:cd15931    117 LIGYGVPFLIVGVSALVYSDGYG-EAK--MCWLSQERGfNWSFLGPVIAIIGINWILF 171
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
 715-873 1.37e-10

brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediates direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320655 [Multi-domain]  Cd Length: 293  Bit Score: 63.94  E-value: 1.37e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  715 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKrcqdpdepppPPRPMLR 794
Cdd:cd15989     42 ILINFCLSIISSNILILVGQTQTHNKGICTMTTAFLHFFFLASFCWVLTEAWQSYMAVTGKIR----------TRLIRKR 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  795 FYLIGGGIPIIVCGITAA-ANIKNYGSRpnaPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQL--------KRHP 864
Cdd:cd15989    112 FLCLGWGLPALVVAISMGfTKAKGYGTP---HYCWLSLEGGlLYAFVGPAAAVVLVNMVIGILVFNKLvsrdgildKKLK 188


                   ....*....
gi 2462595283  865 ERKYELKEP 873
Cdd:cd15989    189 HRAGQMSEP 197
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
 718-863 3.09e-10

Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of seven-transmembrane G protein-coupled receptors; Group I adhesion GPCRs consist of latrophilins (also called lectomedins or latrotoxin receptors) and ETL (EGF-TM7-latrophilin-related protein. These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320380 [Multi-domain]  Cd Length: 257  Bit Score: 62.14  E-value: 3.09e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 797
Cdd:cd15252     42 NLCISLFLAELVFLIGINTTTNKIFCSVIAGLLHYFFLAAFAWMFIEGIQLYLMLVE---------VFENEGSRHKNFYI 112

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  798 IGGGIPIIVCGITAAANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 863
Cdd:cd15252    113 FGYGSPAVIVGVSAALGYRYYGT---TKVCWLSTENYfIWSFIGPATLIILLNLIFLGVAIYKMFRH 176
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
 715-860 4.47e-10

brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediates direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320654 [Multi-domain]  Cd Length: 291  Bit Score: 62.28  E-value: 4.47e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  715 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKrcqdpdepppPPRPMLR 794
Cdd:cd15988     40 ILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFLSSFCWVLTEAWQSYLAVIGRMR----------TRLVRKR 109

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462595283  795 FYLIGGGIPIIVCGITAA-ANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQL 860
Cdd:cd15988    110 FLCLGWGLPALVVAVSVGfTRTKGYGT---ASYCWLSLEGGlLYAFVGPAAVIVLVNMLIGIIVFNKL 174
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
 718-854 6.98e-10

Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320673 [Multi-domain]  Cd Length: 258  Bit Score: 61.09  E-value: 6.98e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdePPPPPRPMLRFYL 797
Cdd:cd16007     42 NLCINLFLAELLFLIGIDKTQYQIACPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVE----------VFESEYSRKKYYY 111

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462595283  798 IGGGI-PIIVCGITAAANIKNYGSRPNapyCWMAWEPS-LGAFYGPASFITFVNCMYFL 854
Cdd:cd16007    112 LCGYCfPALVVGISAAIDYRSYGTEKA---CWLRVDNYfIWSFIGPVSFVIVVNLVFLM 167
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
 715-860 4.12e-09

brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Brain-specific angiogenesis inhibitors (BAI1-3) constitute the group VII of cell-adhesion receptors that have been implicated in vascularization of glioblastomas. They belong to the B2 subfamily of class B GPCRs, are predominantly expressed in the brain, and are only present in vertebrates. Three BAIs, like all adhesion receptors, are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. For example, BAI1 N-terminus contain an integrin-binding RGD (Arg-Gly-Asp) motif in addition to five thrombospondin type 1 repeats (TSRs), which are known to regulate the anti-angiogenic activity of thrombospondin-1, whereas BAI2 and BAI3 have four TSRs, but do not possess RGD motifs. The TSRs are functionally involved in cell attachment, activation of latent TGF-beta, inhibition of angiogenesis and endothelial cell migration. The TSRs of BAI1 mediates direct binding to phosphatidylserine, which enables both recognition and internalization of apoptotic cells by phagocytes. Thus, BAI1 functions as a phosphatidylserine receptor that forms a trimeric complex with ELMO and Dock180, leading to activation of Rac-GTPase which promotes the binding and phagocytosis of apoptotic cells. BAI3 can also interact with the ELMO-Dock180 complex to activate the Rac pathway and can also bind to secreted C1ql proteins of the C1Q complement family via its N-terminal TSRs. BAI3 and its ligands C1QL1 are highly expressed during synaptogenesis and are involved in synapse specificity. Moreover, BAI2 acts as a transcription repressor to regulate vascular endothelial growth factor (VEGF) expression through interaction with GA-binding protein gamma (GABP). The N-terminal extracellular domains of all three BAIs also contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain, which undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif to generate N- and C-terminal fragments (NTF and CTF), a putative hormone-binding domain (HBD), and multiple N-glycosylation sites. The C-terminus of each BAI subtype ends with a conserved Gln-Thr-Glu-Val (QTEV) motif known to interact with PDZ domain-containing proteins, but only BAI1 possesses a proline-rich region, which may be involved in protein-protein interactions.


Pssm-ID: 320656  Cd Length: 267  Bit Score: 58.85  E-value: 4.12e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  715 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKRcqdpdeppppPRPMLR 794
Cdd:cd15990     43 ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRN----------RIIRKR 112

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462595283  795 FYLIGGGIPIIVCGITAA-ANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQL 860
Cdd:cd15990    113 FLCLGWGLPALVVAISVGfTKAKGYGT---VNYCWLSLEGGlLYAFVGPAAAVVLVNMVIGILVFNKL 177
PCC TIGR00864
polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) ...
 53-154 6.12e-09

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.


Pssm-ID: 188093 [Multi-domain]  Cd Length: 2740  Bit Score: 60.87  E-value: 6.12e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283   53 DLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSslsqgtfdylaslrslefqteyllCDCNILWMHRWVKEKNITVRD--- 129
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFE------------------------CDCGLARLPRWAEEKGVKVRQpea 56

                           90       100
                   ....*....|....*....|....*
gi 2462595283  130 TRCVYPKSLQAQPVTGVKQELLTCD 154
Cdd:TIGR00864   57 ALCAGPGALAGQPLLGIPLLDSGCD 81
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
 718-855 6.91e-09

Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of seven-transmembrane G protein-coupled receptors; The group IV adhesion GPCRs include the cadherin EGF LAG seven-pass G-type receptors (CELSRs) and their Drosophila homolog Flamingo (also known as Starry night). These receptors are also classified as that belongs to the EGF-TM7 group of subfamily B2 adhesion GPCRs, because they contain EGF-like domains. Functionally, the group IV receptors act as key regulators of many physiological processes such as endocrine cell differentiation, neuronal migration, dendrite growth, axon, guidance, lymphatic vessel and valve formation, and planar cell polarity (PCP) during embryonic development. Three mammalian orthologs of Flamingo, Celsr1-3, are widely expressed in the nervous system from embryonic development until the adult stage. Each Celsr exhibits different expression patterns in the developing brain, suggesting that they serve distinct functions. Mutations of CELSR1 cause neural tube defects in the nervous system, while mutations of CELSR2 are associated with coronary heart disease. Moreover, CELSR1 and several other PCP signaling molecules, such as dishevelled, prickle, frizzled, have been shown to be upregulated in B lymphocytes of chronic lymphocytic leukemia patients. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. In the case of CELSR/Flamingo/Starry night, their extracellular domains comprise nine cadherin repeats linked to a series of epidermal growth factor (EGF)-like and laminin globular (G)-like domains. The cadherin repeats contain sequence motifs that mediate calcium-dependent cell-cell adhesion by homophilic interactions. Moreover, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320658  Cd Length: 255  Bit Score: 58.29  E-value: 6.91e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 797
Cdd:cd15992     42 NGATALFLSELVFILGINQADNPFACTVIAILLHFFYLCTFSWLFLEGLHIYRMLSE---------VRDINYGPMRFYYL 112

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  798 IGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWEPSL-GAFYGPASFITFVNC-MYFLS 855
Cdd:cd15992    113 IGWGVPAFITGLAVGLDPEGYG---NPDFCWLSIYDTLiWSFAGPVAFAVSMNVfLYILS 169
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
 718-863 7.83e-09

Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320672 [Multi-domain]  Cd Length: 258  Bit Score: 58.00  E-value: 7.83e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 797
Cdd:cd16006     42 NLCINLFIAEFIFLIGIDKTEYKIACPIFAGLLHFFFLAAFAWMCLEGVQLYLMLVE---------VFESEYSRKKYYYV 112

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  798 IGGGIPIIVCGITAAANIKNYGSRPNapyCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 863
Cdd:cd16006    113 AGYLFPATVVGVSAAIDYKSYGTEKA---CWLRVDNYfIWSFIGPVTFIILLNLIFLVITLCKMVKH 176
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
6-88 8.63e-09

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 59.18  E-value: 8.63e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELKngSFSGLSLLERLDLRNNLISSIDPGAfwGLSSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSS 85
Cdd:COG4886    235 LSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLNL 310


                   ...
gi 2462595283   86 LSQ 88
Cdd:COG4886    311 LEL 313
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
 715-975 2.01e-08

orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B secretin-like receptors of seven-transmembrane G protein-coupled receptors; GPR64 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR97, GPR112, GPR114, and GPR126. GPR64 is mainly expressed in the epididymis of male reproductive tract, and targeted deletion of GPR64 causes sperm stasis and efferent duct blockage due to abnormal fluid reabsorption, resulting in male infertility. GPR64 is also over-expressed in Ewing's sarcoma (ES), as well as upregulated in other carcinomas from kidney, prostate or lung, and promotes invasiveness and metastasis in ES via the upregulation of placental growth factor (PGF) and matrix metalloproteinase (MMP) 1. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 57.14  E-value: 2.01e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  715 MLVNLCFHIFLTCVVFV--GGITQTRNA-SICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRP 791
Cdd:cd15444     40 ILIQLCVALLLLNLVFLldSWIALYKDIvGLCISVAVFLHYFLLVSFTWMGLEAFHMYLALVK--------VFNTYIRKY 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  792 MLRFYLIGGGIPIIVCGITAAANIKNYG-----SRPNAP---YCWMAWEPslgAFY----GPASFITFVNCMYFLSIFIQ 859
Cdd:cd15444    112 ILKFCIVGWGVPAVVVAIVLAVSKDNYGlgsygKSPNGStddFCWINNNI---VFYitvvGYFCVIFLLNISMFIVVLVQ 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  860 LKRhperkyelkepTEEQQRLAANENGEInhQDSMSLSLIStsalenehtfhsqllgasltlllyVALWMFGALAVSLYY 939
Cdd:cd15444    189 LCR-----------IKKQKQLGAQRKTSL--QDLRSVAGIT------------------------FLLGITWGFAFFAWG 231

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 2462595283  940 PLDLVFSFVFgATSLSFSAFFV-VHHCVNREDVRLAW 975
Cdd:cd15444    232 PVNLAFMYLF-AIFNTLQGFFIfIFYCVAKENVRKQW 267
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
 715-977 3.88e-08

Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR112 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR64, GPR97, GPR114, and GPR126. GPR112 is specifically expressed in normal enterochromatin cells and gastrointestinal neuroendocrine carcinoma cells, but its biological function is unknown. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320663  Cd Length: 269  Bit Score: 56.21  E-value: 3.88e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  715 MLVNLCFHIFLTCVVFV--GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRPM 792
Cdd:cd15997     40 ILINLCTALLMLNLVFLlnSWLSSFNNYGLCITVAAFLHYFLLASFTWMGLEAVHMYFALVK--------VFNIYIPNYI 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  793 LRFYLIGGGIPIIVCGITAAANIKNYGS-------RPNAPYCWMAwepSLGAFY----GPASFITFVNCMYFLSIFIQLk 861
Cdd:cd15997    112 LKFCIAGWGIPAVVVALVLAINKDFYGNelssdslHPSTPFCWIQ---DDVVFYisvvAYFCLIFLCNISMFITVLIQI- 187

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  862 rhpeRKYELKEPTEEQQRlaanengeinhqdSMSLSLISTSALenehTFhsqllgasltlllYVAL-WMFGALAvslYYP 940
Cdd:cd15997    188 ----RSMKAKKPSRNWKQ-------------GFLHDLKSVASL----TF-------------LLGLtWGFAFFA---WGP 230

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 2462595283  941 LDLVFSFVFgATSLSFSAFFV-VHHCVNREDVRLAWIM 977
Cdd:cd15997    231 VRIFFLYLF-SICNTLQGFFIfVFHCLMKENVRKQWRI 267
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
6-102 5.93e-08

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 56.48  E-value: 5.93e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELKNGSFSGLSLLERLDLRNNLissidpgAFWGLSSLKRLDLTNNRIGCLNADIFRgLTNLVRLNLSGNLFSS 85
Cdd:COG4886     79 LLLLSLLLLGLTDLGDLTNLTELDLSGNE-------ELSNLTNLESLDLSGNQLTDLPEELAN-LTNLKELDLSNNQLTD 150

                           90
                   ....*....|....*..
gi 2462595283   86 LSQgTFDYLASLRSLEF 102
Cdd:COG4886    151 LPE-PLGNLTNLKSLDL 166
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 718-863 9.68e-08

Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320552 [Multi-domain]  Cd Length: 258  Bit Score: 54.80  E-value: 9.68e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 797
Cdd:cd15436     42 NLCINLFIAELLFLIGINRTQYTIACPIFAGLLHFFFLAAFCWLCLEGVQLYLLLVE---------VFESEYSRRKYFYL 112

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  798 IGGGIPIIVCGITAAANIKNYGSRpnaPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 863
Cdd:cd15436    113 CGYSFPALVVAVSAAIDYRSYGTE---KACWLRVDNYfIWSFIGPVTFVITLNLVFLVITLHKMVSH 176
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
 718-853 1.90e-07

Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled receptors; Latrophilins (also called lectomedins or latrotoxin receptors) belong to Group I adhesion GPCRs, which also include ETL (EGF-TM7-latrophilin-related protein). These receptors are a member of the adhesion family (subclass B2) that belongs to the class B GPCRs. Three subtypes of latrophilins have been identified: LPH1 (latrophilin-1), LPH2, and LPH3. The latrophilin-1 is a brain-specific calcium-independent receptor of alpha-latrotoxin, a potent presynaptic neurotoxin from the venom of the black widow spider that induces massive neurotransmitter release from sensory and motor neurons as well as endocrine cells, leading to nerve-terminal degeneration. Latrophilin-2 and -3, although sharing strong sequence homology to latrophilin-1, do not bind alpha-latrotoxin. While latrophilin-3 is also brain specific, latrophilin-2 is ubiquitously distributed. The endogenous ligands for these two receptors are unknown. ETL, a seven transmembrane receptor containing EGF-like repeats is highly expressed in heart, where developmentally regulated, as well as in normal smooth cells. The function of the ETL is unknown. All adhesion GPCRs possess large N-terminal extracellular domains containing multiple structural motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, coupled to a seven-transmembrane domain. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 53.79  E-value: 1.90e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  718 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKRCQDPDEPpppprpmlrFYL 797
Cdd:cd16005     42 NLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAAFTWMFLEGVQLYIMLVEVFESEHSRRKY---------FYL 112

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  798 IGGGIPIIVCGITAAANIKNYGSRpnaPYCWMAWEPS-LGAFYGPASFITFVNCMYF 853
Cdd:cd16005    113 VGYGMPALIVAVSAAVDYRSYGTD---KVCWLRLDTYfIWSFIGPATLIIMLNVIFL 166
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
 702-858 2.33e-07

orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR128 is an orphan receptor of the adhesion family (subclass B2) that belongs to the class B GPCRs. Expression of GPR128 was detected in the mouse intestinal mucosa and is thought to be involved in energy balance, as its knockout mice showed a decrease in body weight gain and an increase in intestinal contraction frequency compared to wild-type controls. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. These include, for example, EGF (epidermal growth factor)-like domains in CD97, Celsr1 (cadherin family member), Celsr2, Celsr3, EMR1 (EGF-module-containing mucin-like hormone receptor-like 1), EMR2, EMR3, and Flamingo; two laminin A G-type repeats and nine cadherin domains in Flamingo and its human orthologs Celsr1, Celsr2 and Celsr3; olfactomedin-like domains in the latrotoxin receptors; and five or four thrombospondin type 1 repeats in BAI1 (brain-specific angiogenesis inhibitor 1), BAI2 and BAI3. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320385 [Multi-domain]  Cd Length: 303  Bit Score: 54.11  E-value: 2.33e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  702 HHSLIRISLKSWhMLVNLCFHIFLTCVVFVGGITQTRN-------------------------ASICQAVGIILHYSTLA 756
Cdd:cd15257     28 HTRKLRKSSVTW-VLLNLCSSLLLFNIIFTSGVENTNNdyeistvpdretntvllseeyvepdTDVCTAVAALLHYFLLV 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  757 TVLWVGVTARNIYKQVTKKAKrcqdpdepPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAP-------YCWM 829
Cdd:cd15257    107 TFMWNAVYSAQLYLLLIRMMK--------PLPEMFILQASAIGWGIPAVVVAITLGATYRFPTSLPVFTrtyrqeeFCWL 178

                          170       180       190
                   ....*....|....*....|....*....|.
gi 2462595283  830 AWEPSLGAFYGPA--SFITFVNCMYFLSIFI 858
Cdd:cd15257    179 AALDKNFDIKKPLlwGFLLPVGLILITNVIL 209
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 25-87 4.22e-06

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 49.01  E-value: 4.22e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462595283   25 LERLDLRNNLISSIDPgaFWGLSSLKRLDLTNNRIGCLN--ADIFRGLTNLVRLNLSGNLFSSLS 87
Cdd:cd21340    122 LRVLNISGNNIDSLEP--LAPLRNLEQLDASNNQISDLEelLDLLSSWPSLRELDLTGNPVCKKP 184
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 622-661 5.29e-06

GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.


Pssm-ID: 460350  Cd Length: 44  Bit Score: 44.61  E-value: 5.29e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2462595283  622 WDFDLlNGQGGWKSDGCHILYSDENITTIQCYSLSNYAVL 661
Cdd:pfam01825    6 WDFTN-STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 6-59 7.35e-06

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 48.63  E-value: 7.35e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462595283    6 LSNNKISELKngSFSGLSLLERLDLRNNLISSIDP--GAFWGLSSLKRLDLTNNRI 59
Cdd:cd21340    127 ISGNNIDSLE--PLAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDLTGNPV 180
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
 714-871 1.47e-05

orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR56 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR64, GPR97, GPR112, GPR114, and GPR126. GPR56 is involved in the regulation of oligodendrocyte development and myelination in the central nervous system via coupling to G(12/13) proteins, which leads to the activation of RhoA GTPase. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320661  Cd Length: 269  Bit Score: 48.29  E-value: 1.47e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  714 HMlvNLCFHIFLTCVVFVGG--ITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRP 791
Cdd:cd15995     41 HM--NLLLAIFLLDTSFLISepLALTGSEAACRAGGMFLHFSLLACLTWMGIEGYNLYRLVVE--------VFNTYVPHF 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  792 MLRFYLIGGGIPIIVCGITAAANIKNYG-----------SRPNAPYCWMAwEPSLGAF--YGPASFITFVNCMYFLSIFI 858
Cdd:cd15995    111 LLKLCAVGWGLPIFLVTLIFLVDQDNYGpiilavhrspeKVTYATICWIT-DSLISNItnLGLFSLVFLFNMAMLATMVV 189

                          170
                   ....*....|...
gi 2462595283  859 QLKRHPERKYELK 871
Cdd:cd15995    190 EILRLRPRTHKWS 202
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 621-664 2.49e-05

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.


Pssm-ID: 197639  Cd Length: 49  Bit Score: 42.76  E-value: 2.49e-05
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 2462595283   621 RWDFDllngQGGWKSDGCHILYSDENITTIQCYSLSNYAVLMDL 664
Cdd:smart00303    7 FWDES----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDV 46
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
 715-975 3.18e-05

orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR126 is an orphan receptor that has been classified as that belongs to the Group VIII of adhesion GPCRs. Other members of the Group VII include orphan GPCRs such as GPR56, GPR64, GPR97, GPR112, and GPR114. GPR126 is required in Schwann cells for proper differentiation and myelination via G-Protein Activation. GPR126 is believed to couple to G(s)-protein, which leads to activation of adenylate cyclase for cAMP production. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320662  Cd Length: 271  Bit Score: 47.19  E-value: 3.18e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  715 MLVNLCFHIFLTCVVFV--GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRPM 792
Cdd:cd15996     40 ILMNLSTALLFLNLVFLldGWIASFEIDELCITVAVLLHFFLLATFTWMGLEAIHMYIALVK--------VFNTYIRRYI 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  793 LRFYLIGGGIPIIVCGITAAANIKNYG---------SRPNAPYCWMAwEPSLgaFY----GPASFITFVNCMYFLSIFIQ 859
Cdd:cd15996    112 LKFCIIGWGLPALIVSIVLASTNDNYGygyygkdkdGQGGDEFCWIK-NPVV--FYvtcaAYFGIMFLMNVAMFIVVMVQ 188

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  860 L-KRHPER-KYELKEPTEEQQRlaanengeinhqdsmslSLISTSALenehtfhsqllgasltlllyvaLWMFGALAVSL 937
Cdd:cd15996    189 IcGRNGKRsNRTLREEILRNLR-----------------SVVSLTFL----------------------LGMTWGFAFFA 229

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 2462595283  938 YYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAW 975
Cdd:cd15996    230 WGPVNLAFMYLFTIFNSLQGLFIFVFHCALKENVQKQW 267
LRR_4 pfam12799
Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a ...
 25-64 4.35e-05

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.


Pssm-ID: 463713 [Multi-domain]  Cd Length: 44  Bit Score: 41.85  E-value: 4.35e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2462595283   25 LERLDLRNNLISSIDPgaFWGLSSLKRLDLT-NNRIGCLNA 64
Cdd:pfam12799    3 LEVLDLSNNQITDIPP--LAKLPNLETLDLSgNNKITDLSD 41
LRRCT smart00082
Leucine rich repeat C-terminal domain;
107-141 7.64e-05

Leucine rich repeat C-terminal domain;


Pssm-ID: 214507 [Multi-domain]  Cd Length: 51  Bit Score: 41.26  E-value: 7.64e-05
                            10        20        30
                    ....*....|....*....|....*....|....*..
gi 2462595283   107 LLCDCNILWMHRWVKEKNITVR--DTRCVYPKSLQAQ 141
Cdd:smart00082    3 FICDCELRWLLRWLQANEHLQDpvDLRCASPSSLRGP 39
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 281-334 7.96e-05

Hormone receptor domain; This extracellular domain contains four conserved cysteines that probably for disulphide bridges. The domain is found in a variety of hormone receptors. It may be a ligand binding domain.


Pssm-ID: 397086  Cd Length: 64  Bit Score: 41.59  E-value: 7.96e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462595283  281 WPRTLAGITAYLQCTRNTHGSgiypgnpQDERKAWRRCDRGGFWAD---DDYSRCQY 334
Cdd:pfam02793   14 WPRTPAGETVEVPCPDYFSGF-------DPRGNASRNCTEDGTWSEhppSNYSNCTS 63
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
 717-858 1.34e-04

orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR97 is an orphan receptor that has been classified into the group VIII of adhesion GPCRs. Other members of the Group VII include GPR56, GPR64, GPR112, GPR114, and GPR126. GPR97 is identified as a lymphatic adhesion receptor that is specifically expressed in lymphatic endothelium, but not in blood vascular endothelium, and is shown to regulate migration of lymphatic endothelial cells via the small GTPases RhoA and cdc42. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in cell-cell adhesion and cell-matrix interactions, that are coupled to a class B seven-transmembrane domain. Furthermore, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR- autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions.


Pssm-ID: 320558 [Multi-domain]  Cd Length: 277  Bit Score: 45.17  E-value: 1.34e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  717 VNLCFHIFLTCVVFV--GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRPMLR 794
Cdd:cd15442     46 VNLSSSLLLLNLAFLlnSGVSSRAHPGLCKALGGVTHYFLLCCFTWMAIEAFHLYLLAIK--------VFNTYIHHYFAK 117

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  795 FYLIGGGIPIIVCGITAAAN------IKNYGSRPNAPYCWMAwEPSLGAFYgpasfITfvNCMYFLSIFI 858
Cdd:cd15442    118 LCLVGWGFPALVVTITGSINsygaytIMDMANRTTLHLCWIN-SKHLTVHY-----IT--VCGYFGLTFL 179
LRR_RI cd00116
Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 ...
 6-115 1.71e-04

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).


Pssm-ID: 238064 [Multi-domain]  Cd Length: 319  Bit Score: 45.04  E-value: 1.71e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISElKNGS-----FSGLSLLERLDLRNNLISS-----IDPGAFWGLSSLKRLDLTNNRIGCLNA-DIFRGLTN-- 72
Cdd:cd00116    200 LNNNGLTD-EGASalaetLASLKSLEVLNLGDNNLTDagaaaLASALLSPNISLLTLSLSCNDITDDGAkDLAEVLAEke 278

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 2462595283   73 -LVRLNLSGNLFSSLSQgtfdYLASLRSLEFQteyllCDCNILW 115
Cdd:cd00116    279 sLLELDLRGNKFGEEGA----QLLAESLLEPG-----NELESLW 313
LRR_RI cd00116
Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 ...
 5-100 2.05e-04

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).


Pssm-ID: 238064 [Multi-domain]  Cd Length: 319  Bit Score: 45.04  E-value: 2.05e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    5 ILSNNKISelkNGS-------FSGLSLLERLDLRNNLISsiDPG------AFWGLSSLKRLDLTNNRIGCLN----ADIF 67
Cdd:cd00116    143 VLGRNRLE---GAScealakaLRANRDLKELNLANNGIG--DAGiralaeGLKANCNLEVLDLNNNGLTDEGasalAETL 217

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 2462595283   68 RGLTNLVRLNLSGNLFSS-----LSQGTFDYLASLRSL 100
Cdd:cd00116    218 ASLKSLEVLNLGDNNLTDagaaaLASALLSPNISLLTL 255
LRR_5 pfam13306
BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich ...
 2-98 2.88e-04

BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich repeats. This family contains a large number of BSPA-like surface antigens from Trichomonas vaginalis.


Pssm-ID: 463839 [Multi-domain]  Cd Length: 127  Bit Score: 42.15  E-value: 2.88e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    2 LIEILSNNKISELKNGSFSGlSLLERLDLRNNlISSIDPGAFWGLSSLKRLDLTNNrIGCLNADIFRGlTNLVRLNLSGN 81
Cdd:pfam13306   36 LKSITLPSSLTSIGSYAFYN-CSLTSITIPSS-LTSIGEYAFSNCSNLKSITLPSN-LTSIGSYAFSN-CSLKSITIPSS 111

                           90
                   ....*....|....*..
gi 2462595283   82 LfSSLSQGTFDYLASLR 98
Cdd:pfam13306  112 V-TTIGSYAFSNCSNLK 127
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 6-84 3.10e-04

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 45.22  E-value: 3.10e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKIS-ELKNgsFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFS 84
Cdd:PLN00113   459 LARNKFFgGLPD--SFGSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLS 536
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 6-101 4.00e-04

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.


Pssm-ID: 411060 [Multi-domain]  Cd Length: 220  Bit Score: 43.24  E-value: 4.00e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELKNgsFSGLSLLERLDLRNNLISSIDpgafwGLSSLKRL---DLTNNRIGCLnaDIFRGLTNLVRLNLSGNL 82
Cdd:cd21340      9 LNDKNITKIDN--LSLCKNLKVLYLYDNKITKIE-----NLEFLTNLthlYLQNNQIEKI--ENLENLVNLKKLYLGGNR 79

                           90
                   ....*....|....*....
gi 2462595283   83 FSSLSQgtfdyLASLRSLE 101
Cdd:cd21340     80 ISVVEG-----LENLTNLE 93
LRR_4 pfam12799
Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a ...
 48-81 4.51e-04

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.


Pssm-ID: 463713 [Multi-domain]  Cd Length: 44  Bit Score: 39.15  E-value: 4.51e-04
                           10        20        30
                   ....*....|....*....|....*....|....
gi 2462595283   48 SLKRLDLTNNRIGCLnaDIFRGLTNLVRLNLSGN 81
Cdd:pfam12799    2 NLEVLDLSNNQITDI--PPLAKLPNLETLDLSGN 33
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
 716-862 4.91e-04

orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of seven-transmembrane G protein-coupled receptors; group VI adhesion GPCRs consist of orphan receptors GPR110, GPR111, GPR113, GPR115, GPR116, and closely related proteins. The adhesion receptors are characterized by the presence of large N-terminal extracellular domains containing multiple adhesion motifs, which play critical roles in ligand recognition as well as cell-cell adhesion and cell-matrix interactions, linked by a stalk region to a class B seven-transmembrane domain. GPR110 possesses a SEA box in the N-terminal has been identified as an oncogene over-expressed in lung and prostate cancer. GPR113 contains a hormone binding domain and one EGF (epidermal grown factor) domain. GPR112 has extremely long N-terminus (about 2,400 amino acids) containing a number of Ser/Thr-rich glycosylation sites and a pentraxin (PTX) domain. GPR116 has two C2-set immunoglobulin-like repeats, which is found in the members of the immunoglobulin superfamily of cell surface proteins, and a SEA (sea urchin sperm protein, enterokinase, and a grin)-box, which is present in the extracellular domain of the transmembrane mucin (MUC) family and known to enhance O-glycosylation. In addition, almost all adhesion receptors, except GPR123, contain an evolutionarily conserved GPCR-autoproteolysis inducing (GAIN) domain that undergoes autoproteolytic processing at the GPCR proteolysis site (GPS) motif located immediately N-terminal to the first transmembrane region, to generate N- and C-terminal fragments (NTF and CTF), which may serve important biological functions. However, several adhesion GPCRs, including GPR 111, GPR115, and CELSR1, are predicted to be non-cleavable at the GAIN domain because of the lack of a consensus catalytic triad sequence (His-Leu-Ser/Thr) within their GPS.


Pssm-ID: 320598 [Multi-domain]  Cd Length: 268  Bit Score: 43.46  E-value: 4.91e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  716 LVNLCFHIFLTCVVFVGGI---TQTRNASICQAVGIILHYSTLATVLWVGVTA-----RNIY--KQVTKKAkrcqdpdep 785
Cdd:cd15932     46 LVNIALSLLIADIWFIIGAaisTPPNPSPACTAATFFIHFFYLALFFWMLTLGlllfyRLVLvfHDMSKST--------- 116

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  786 pppprPMLRFYLIGGGIPIIVCGITAAANIKNYG-SRPNApyCWMAWEPS--LGAFYGPASFITFVNCMYFLSIFIQLKR 862
Cdd:cd15932    117 -----MMAIAFSLGYGCPLIIAIITVAATAPQGGyTRKGV--CWLNWDKTkaLLAFVIPALAIVVVNFIILIVVIFKLLR 189
HormR smart00008
Domain present in hormone receptors;
281-334 5.76e-04

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 39.42  E-value: 5.76e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462595283   281 WPRTLAGITAYLQCTRNThgSGIYPGNpqderKAWRRCDRGGFWA--DDDYSRCQY 334
Cdd:smart00008   15 WPQTPAGQLVEVPCPKYF--SGFSYKT-----GASRNCTENGGWSppFPNYSNCTS 63
LRR_5 pfam13306
BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich ...
 2-102 7.85e-04

BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich repeats. This family contains a large number of BSPA-like surface antigens from Trichomonas vaginalis.


Pssm-ID: 463839 [Multi-domain]  Cd Length: 127  Bit Score: 40.61  E-value: 7.85e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    2 LIEILSNNKISELKNGSFSGLSLLERLDLRNNLIsSIDPGAFWGlSSLKRLDLTNN--RIGcLNAdiFRGLTNLVRLNLS 79
Cdd:pfam13306   13 LTSITIPSSLTSIGEYAFSNCTSLKSITLPSSLT-SIGSYAFYN-CSLTSITIPSSltSIG-EYA--FSNCSNLKSITLP 87

                           90       100
                   ....*....|....*....|...
gi 2462595283   80 GNLfSSLSQGTFdYLASLRSLEF 102
Cdd:pfam13306   88 SNL-TSIGSYAF-SNCSLKSITI 108
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
 706-851 7.91e-04

insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Nilaparvata lugens (brown planthopper) and its closely related proteins from mollusks and annelid worms. They belong to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. The class B GPCRs have been identified in all the vertebrates, from fishes to mammals, as well as invertebrates including Caenorhabditis elegans and Drosophila melanogaster, but are not present in plants, fungi, or prokaryotes.


Pssm-ID: 320388 [Multi-domain]  Cd Length: 267  Bit Score: 42.64  E-value: 7.91e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  706 IRIslkswHM-------LVNLCFHIFLTCVVFVGGITQtRNASICQAVGIILHYSTLATVLWV---GVTARNIYKQVTKK 775
Cdd:cd15260     37 ITI-----HMnlfisfaLNNLLWIVWYKLVVDNPEVLL-ENPIWCQALHVLLQYFMVCNYFWMfceGLYLHTVLVVAFIS 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  776 AKRCqdpdeppppprpMLRFYLIGGGIPIIVCGITAAAnikNYGSRPNAPYCWMAWEPSLGAFYGP------ASFITFVN 849
Cdd:cd15260    111 EKSL------------MRWFIAIGWGVPLVITAIYAGV---RASLPDDTERCWMEESSYQWILIVPvvlsllINLIFLIN 175


                   ..
gi 2462595283  850 CM 851
Cdd:cd15260    176 IV 177
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 6-104 2.53e-03

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 42.14  E-value: 2.53e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    6 LSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGA-FWGLSSLKRLDLTNNRigcLNADIFRG-LTNLVRLNLSGNLF 83
Cdd:PLN00113    76 LSGKNISGKISSAIFRLPYIQTINLSNNQLSGPIPDDiFTTSSSLRYLNLSNNN---FTGSIPRGsIPNLETLDLSNNML 152

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 2462595283   84 SS---LSQGTFD------------------YLASLRSLEFQT 104
Cdd:PLN00113   153 SGeipNDIGSFSslkvldlggnvlvgkipnSLTNLTSLEFLT 194
LRR smart00370
Leucine-rich repeats, outliers;
22-45 3.68e-03

Leucine-rich repeats, outliers;


Pssm-ID: 197688 [Multi-domain]  Cd Length: 24  Bit Score: 35.79  E-value: 3.68e-03
                            10        20
                    ....*....|....*....|....
gi 2462595283    22 LSLLERLDLRNNLISSIDPGAFWG 45
Cdd:smart00370    1 LPNLRELDLSNNQLSSLPPGAFQG 24
LRR_TYP smart00369
Leucine-rich repeats, typical (most populated) subfamily;
22-45 3.68e-03

Leucine-rich repeats, typical (most populated) subfamily;


Pssm-ID: 197687 [Multi-domain]  Cd Length: 24  Bit Score: 35.79  E-value: 3.68e-03
                            10        20
                    ....*....|....*....|....
gi 2462595283    22 LSLLERLDLRNNLISSIDPGAFWG 45
Cdd:smart00369    1 LPNLRELDLSNNQLSSLPPGAFQG 24
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 167-259 3.74e-03

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.


Pssm-ID: 214653 [Multi-domain]  Cd Length: 85  Bit Score: 37.87  E-value: 3.74e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283   167 SHRQVVFEGDSLPFQCMASYiDQDMQVLWYQDGriVETDESQGIFVEKNMIHNCSLiasalTISNIQAGSTGNWGCHVQT 246
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASG-SPPPEVTWYKQG--GKLLAESGRFSVSRSGSTSTL-----TISNVTPEDSGTYTCAATN 72

                            90
                    ....*....|...
gi 2462595283   247 KRGNNTRTVDIVV 259
Cdd:smart00410   73 SSGSASSGTTLTV 85
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 160-244 4.66e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 37.16  E-value: 4.66e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  160 PSFYMTPSHrQVVFEGDSLPFQCMASYIDQDmQVLWYQDGRIVETDESQGIFVEKNMihncsliaSALTISNIQAGSTGN 239
Cdd:pfam13927    2 PVITVSPSS-VTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRSRSLSGSN--------STLTISNVTRSDAGT 71


                   ....*
gi 2462595283  240 WGCHV 244
Cdd:pfam13927   72 YTCVA 76
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 8-101 6.53e-03

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 40.99  E-value: 6.53e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283    8 NNKISELKNgSFSGLSLLERLDL-RNNLISSIdPGAFWGLSSLKRLDLTNNRI-GCLNADIFrGLTNLVRLNLSGNlfsS 85
Cdd:PLN00113   222 NNLSGEIPY-EIGGLTSLNHLDLvYNNLTGPI-PSSLGNLKNLQYLFLYQNKLsGPIPPSIF-SLQKLISLDLSDN---S 295

                           90
                   ....*....|....*.
gi 2462595283   86 LSQGTFDYLASLRSLE 101
Cdd:PLN00113   296 LSGEIPELVIQLQNLE 311
PLN03150 PLN03150
hypothetical protein; Provisional
 20-84 7.48e-03

hypothetical protein; Provisional


Pssm-ID: 178695 [Multi-domain]  Cd Length: 623  Bit Score: 40.57  E-value: 7.48e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462595283   20 SGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFS 84
Cdd:PLN03150   439 SKLRHLQSINLSGNSIRGNIPPSLGSITSLEVLDLSYNSFNGSIPESLGQLTSLRILNLNGNSLS 503
I-set pfam07679
Immunoglobulin I-set domain;
160-242 9.52e-03

Immunoglobulin I-set domain;


Pssm-ID: 400151 [Multi-domain]  Cd Length: 90  Bit Score: 36.85  E-value: 9.52e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462595283  160 PSFyMTPSHRQVVFEGDSLPFQCMASYiDQDMQVLWYQDGRIVETDesqGIFVEKNMIHNCSliasaLTISNIQAGSTGN 239
Cdd:pfam07679    1 PKF-TQKPKDVEVQEGESARFTCTVTG-TPDPEVSWFKDGQPLRSS---DRFKVTYEGGTYT-----LTISNVQPDDSGK 70


                   ...
gi 2462595283  240 WGC 242
Cdd:pfam07679   71 YTC 73
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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