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Conserved domains on  [gi|59823631|ref|NP_660333|]
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adhesion G protein-coupled receptor A3 precursor [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 ...
 756-1063 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 59823631  756 ASLLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYS 835
Cdd:cd15999    1 ADLLHPVVYATAVVLLLCLLTIIVSYIYHHSLVRISRKSWHMLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  836 TLATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 915
Cdd:cd15999   81 TLATVLWVGVTARNIYKQVTRKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  916 SLGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAANENGEINHQDS----MSLSLISTSALENEHT 991
Cdd:cd15999  161 SLGAFYGPAGFIIFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAASEHGELNHQDSgsssASCSLVSTSALENEHS 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 59823631  992 FHSQLLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWIMTCCP 1063
Cdd:cd15999  241 FQAQLLGASLALFLYVALWIFGALAVSLYYPMDLVFSCLFGATCLSLGAFLVVHHCVNREDVRRAWIATCCP 312
LRR_8 pfam13855
Leucine rich repeat;
85-141 7.19e-18

Leucine rich repeat;


:

Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 78.72  E-value: 7.19e-18
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631     85 TLILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRI 141
Cdd:pfam13855    5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
76-190 1.57e-13

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


:

Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 74.20  E-value: 1.57e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   76 PDTLPNRT--VTLILSNNKISELkNGSFSGLSLLERLDLRNNLISSIDpgAFWGLSSLKRLDLTNNRIGCLNADIfrGLT 153
Cdd:COG4886  198 PEPLGNLTnlEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPPLA--NLT 272

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 59823631  154 NLVRLNLSGNLFSSLSQGTFDYLASLRSLEFQTEYLL 190
Cdd:COG4886  273 NLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLN 309
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 704-743 5.64e-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: 5.64e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 59823631    704 WDFDLlNGQGGWKSDGCHILYSDENITTIQCYSLSNYAVL 743
Cdd:pfam01825    6 WDFTN-STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 363-416 8.83e-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: 8.83e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631    363 WPRTLAGITAYLQCTRNTHGSgiypgnpQDERKAWRRCDRGGFWAD---DDYSRCQY 416
Cdd:pfam02793   14 WPRTPAGETVEVPCPDYFSGF-------DPRGNASRNCTEDGTWSEhppSNYSNCTS 63
LRRCT smart00082
Leucine rich repeat C-terminal domain;
189-223 9.73e-05

Leucine rich repeat C-terminal domain;


:

Pssm-ID: 214507 [Multi-domain]  Cd Length: 51  Bit Score: 41.26  E-value: 9.73e-05
                            10        20        30
                    ....*....|....*....|....*....|....*..
gi 59823631     189 LLCDCNILWMHRWVKEKNITVR--DTRCVYPKSLQAQ 223
Cdd:smart00082    3 FICDCELRWLLRWLQANEHLQDpvDLRCASPSSLRGP 39
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 249-341 3.99e-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: 3.99e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631     249 SHRQVVFEGDSLPFQCMASYiDQDMQVLWYQDGriVETDESQGIFVEKNMIHNCSLiasalTISNIQAGSTGNWGCHVQT 328
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASG-SPPPEVTWYKQG--GKLLAESGRFSVSRSGSTSTL-----TISNVTPEDSGTYTCAATN 72

                            90
                    ....*....|...
gi 59823631     329 KRGNNTRTVDIVV 341
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 ...
 756-1063 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 59823631  756 ASLLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYS 835
Cdd:cd15999    1 ADLLHPVVYATAVVLLLCLLTIIVSYIYHHSLVRISRKSWHMLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  836 TLATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 915
Cdd:cd15999   81 TLATVLWVGVTARNIYKQVTRKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  916 SLGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAANENGEINHQDS----MSLSLISTSALENEHT 991
Cdd:cd15999  161 SLGAFYGPAGFIIFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAASEHGELNHQDSgsssASCSLVSTSALENEHS 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 59823631  992 FHSQLLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWIMTCCP 1063
Cdd:cd15999  241 FQAQLLGASLALFLYVALWIFGALAVSLYYPMDLVFSCLFGATCLSLGAFLVVHHCVNREDVRRAWIATCCP 312
LRR_8 pfam13855
Leucine rich repeat;
85-141 7.19e-18

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 78.72  E-value: 7.19e-18
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631     85 TLILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRI 141
Cdd:pfam13855    5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
85-183 6.36e-17

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


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 84.99  E-value: 6.36e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   85 TLILSNNKISELKNgSFSGLSLLERLDLRNNLISSIdPGAFWGLSSLKRLDLTNNRIGCLNADIFrGLTNLVRLNLSGNL 164
Cdd:COG4886  140 ELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPEPLG-NLTNLEELDLSGNQ 216

                         90
                 ....*....|....*....
gi 59823631  165 FSSLSQGtfdyLASLRSLE 183
Cdd:COG4886  217 LTDLPEP----LANLTNLE 231
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
76-190 1.57e-13

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


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 74.20  E-value: 1.57e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   76 PDTLPNRT--VTLILSNNKISELkNGSFSGLSLLERLDLRNNLISSIDpgAFWGLSSLKRLDLTNNRIGCLNADIfrGLT 153
Cdd:COG4886  198 PEPLGNLTnlEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPPLA--NLT 272

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 59823631  154 NLVRLNLSGNLFSSLSQGTFDYLASLRSLEFQTEYLL 190
Cdd:COG4886  273 NLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLN 309
LRR_8 pfam13855
Leucine rich repeat;
129-182 4.50e-12

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 62.16  E-value: 4.50e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 59823631    129 SSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSSLSQGTFDYLASLRSL 182
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYL 54
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 77-183 7.29e-12

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: 66.35  E-value: 7.29e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   77 DTLPNRTvTLILSNNKISELKNgsFSGLSLLERLDLRNNLISSI---------------------------DPGAFWGLS 129
Cdd:cd21340   43 EFLTNLT-HLYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVVeglenltnleelhienqrlppgekltfDPRSLAALS 119

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 59823631  130 -SLKRLDLTNNRIGCLNAdiFRGLTNLVRLNLSGNLFSSLSQgTFDYLASLRSLE 183
Cdd:cd21340  120 nSLRVLNISGNNIDSLEP--LAPLRNLEQLDASNNQISDLEE-LLDLLSSWPSLR 171
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 796-1043 1.76e-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: 65.76  E-value: 1.76e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    796 HMlvNLCFHIFLTCVVFVGGITQTRNASI--------CQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEP 867
Cdd:pfam00002   40 HL--NLFASFILRALLFLVGDAVLFNKQDldhcswvgCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVE---------VF 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    868 PPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWE-PSLGAFYGPASFITFVNCMYFLSIFIQLKRHp 946
Cdd:pfam00002  109 FSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYG---EDDGCWLSNEnGLWWIIRGPILLIILVNFIIFINIVRILVQK- 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    947 erkyeLKEPTEEQQRLAanengeinhqdSMSLSLISTSALenehtfhsqllgasltlllyVAL----WMFGALAVSLYYP 1022
Cdd:pfam00002  185 -----LRETNMGKSDLK-----------QYRRLAKSTLLL--------------------LPLlgitWVFGLFAFNPENT 228

                          250       260
                   ....*....|....*....|.
gi 59823631   1023 LDLVFSFVFGATSlSFSAFFV 1043
Cdd:pfam00002  229 LRVVFLYLFLILN-SFQGFFV 248
PCC TIGR00864
polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) ...
 135-236 6.86e-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: 6.86e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    135 DLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSslsqgtfdylaslrslefqteyllCDCNILWMHRWVKEKNITVRD--- 211
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFE------------------------CDCGLARLPRWAEEKGVKVRQpea 56

                           90       100
                   ....*....|....*....|....*
gi 59823631    212 TRCVYPKSLQAQPVTGVKQELLTCD 236
Cdd:TIGR00864   57 ALCAGPGALAGQPLLGIPLLDSGCD 81
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 704-743 5.64e-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: 5.64e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 59823631    704 WDFDLlNGQGGWKSDGCHILYSDENITTIQCYSLSNYAVL 743
Cdd:pfam01825    6 WDFTN-STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 703-746 2.66e-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: 2.66e-05
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 59823631     703 RWDFDllngQGGWKSDGCHILYSDENITTIQCYSLSNYAVLMDL 746
Cdd:smart00303    7 FWDES----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDV 46
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 363-416 8.83e-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: 8.83e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631    363 WPRTLAGITAYLQCTRNTHGSgiypgnpQDERKAWRRCDRGGFWAD---DDYSRCQY 416
Cdd:pfam02793   14 WPRTPAGETVEVPCPDYFSGF-------DPRGNASRNCTEDGTWSEhppSNYSNCTS 63
LRRCT smart00082
Leucine rich repeat C-terminal domain;
189-223 9.73e-05

Leucine rich repeat C-terminal domain;


Pssm-ID: 214507 [Multi-domain]  Cd Length: 51  Bit Score: 41.26  E-value: 9.73e-05
                            10        20        30
                    ....*....|....*....|....*....|....*..
gi 59823631     189 LLCDCNILWMHRWVKEKNITVR--DTRCVYPKSLQAQ 223
Cdd:smart00082    3 FICDCELRWLLRWLQANEHLQDpvDLRCASPSSLRGP 39
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 81-186 3.51e-04

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 45.22  E-value: 3.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    81 NRTVTLILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGA-FWGLSSLKRLDLTNNRigcLNADIFRG-LTNLVRL 158
Cdd:PLN00113   69 SRVVSIDLSGKNISGKISSAIFRLPYIQTINLSNNQLSGPIPDDiFTTSSSLRYLNLSNNN---FTGSIPRGsIPNLETL 145

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 59823631   159 NLSGNLFSS---LSQGTFD------------------YLASLRSLEFQT 186
Cdd:PLN00113  146 DLSNNMLSGeipNDIGSFSslkvldlggnvlvgkipnSLTNLTSLEFLT 194
HormR smart00008
Domain present in hormone receptors;
363-416 6.92e-04

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 39.42  E-value: 6.92e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 59823631     363 WPRTLAGITAYLQCTRNThgSGIYPGNpqderKAWRRCDRGGFWA--DDDYSRCQY 416
Cdd:smart00008   15 WPQTPAGQLVEVPCPKYF--SGFSYKT-----GASRNCTENGGWSppFPNYSNCTS 63
LRR smart00370
Leucine-rich repeats, outliers;
104-127 3.88e-03

Leucine-rich repeats, outliers;


Pssm-ID: 197688 [Multi-domain]  Cd Length: 24  Bit Score: 35.79  E-value: 3.88e-03
                            10        20
                    ....*....|....*....|....
gi 59823631     104 LSLLERLDLRNNLISSIDPGAFWG 127
Cdd:smart00370    1 LPNLRELDLSNNQLSSLPPGAFQG 24
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 249-341 3.99e-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: 3.99e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631     249 SHRQVVFEGDSLPFQCMASYiDQDMQVLWYQDGriVETDESQGIFVEKNMIHNCSLiasalTISNIQAGSTGNWGCHVQT 328
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASG-SPPPEVTWYKQG--GKLLAESGRFSVSRSGSTSTL-----TISNVTPEDSGTYTCAATN 72

                            90
                    ....*....|...
gi 59823631     329 KRGNNTRTVDIVV 341
Cdd:smart00410   73 SSGSASSGTTLTV 85
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 242-326 5.38e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 37.16  E-value: 5.38e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    242 PSFYMTPSHrQVVFEGDSLPFQCMASYIDQDmQVLWYQDGRIVETDESQGIFVEKNMihncsliaSALTISNIQAGSTGN 321
Cdd:pfam13927    2 PVITVSPSS-VTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRSRSLSGSN--------STLTISNVTRSDAGT 71


                   ....*
gi 59823631    322 WGCHV 326
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 ...
 756-1063 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 59823631  756 ASLLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYS 835
Cdd:cd15999    1 ADLLHPVVYATAVVLLLCLLTIIVSYIYHHSLVRISRKSWHMLVNLCFHIFLTCAVFVGGINQTRNASVCQAVGIILHYS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  836 TLATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 915
Cdd:cd15999   81 TLATVLWVGVTARNIYKQVTRKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCWMAWEP 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  916 SLGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAANENGEINHQDS----MSLSLISTSALENEHT 991
Cdd:cd15999  161 SLGAFYGPAGFIIFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAASEHGELNHQDSgsssASCSLVSTSALENEHS 240

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 59823631  992 FHSQLLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWIMTCCP 1063
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 ...
 756-1061 1.49e-112

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: 353.60  E-value: 1.49e-112
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  756 ASLLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYS 835
Cdd:cd15259    1 FELLHPVVYAGAALCLLCLLATIITYIVFHRLIRISRKGRHMLVNLCLHLLLTCVVFVGGINRTANQLVCQAVGILLHYS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  836 TLATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSrpnAPYCWMAWEP 915
Cdd:cd15259   81 TLCTLLWVGVTARNMYKQVTKTAKPPQDEDQPPRPPKPMLRFYLIGWGIPLIICGITAAVNLDNYST---YDYCWLAWDP 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  916 SLGAFYGPASFITFVNCMYFLSIFIQLKRHPERkyelkepteeqqrlaanengeinhqdsmslslistsalenehtFHSQ 995
Cdd:cd15259  158 SLGAFYGPAALIVLVNCIYFLRIYCQLKGAPVS-------------------------------------------FQSQ 194

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 59823631  996 LLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWIMTC 1061
Cdd:cd15259  195 LRGAVITLFLYVAMWACGALAVSQRYFLDLVFSCLYGATCSSLGLFVLIHHCLSREDVRQSWRQCC 260
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
 758-1063 3.00e-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: 345.40  E-value: 3.00e-109
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  758 LLHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTL 837
Cdd:cd16000    3 FLHPVVYACTAVMLLCLFASIITYIVHHSTIRISRKGWHMLLNFCFHTALTFAVFAGGINRTKYPIICQAVGIVLHYSTL 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  838 ATVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSR-PNAPYCWMAWEPS 916
Cdd:cd16000   83 STMLWIGVTARNIYKQVTKKPHLCQDTDQPPYPKQPLLRFYLVSGGVPFIICGITAATNINNYGTEdEDTPYCWMAWEPS 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  917 LGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKepteeqqrlaanengeinhqdsmslslistsaleNEHTFHSQL 996
Cdd:cd16000  163 LGAFYGPVAFIVLVTCIYFLCTYVQLRRHPERKYELK----------------------------------NEHSFKAQL 208

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631  997 LGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWiMTCCP 1063
Cdd:cd16000  209 RAAAFTLFLFTATWAFGALAVSQGHFLDMIFSCLYGAFCVTLGLFILIHHCAKRDDVWHCW-WSCCP 274
7tmB2_GPR124 cd15998
G protein-coupled receptor 124, member of the class B2 family of seven-transmembrane G ...
 759-1063 8.91e-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: 8.91e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  759 LHPVVYTTAIILLLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLA 838
Cdd:cd15998    4 LHPVVYPCTALLLLCLFSTIITYILNHSSIHVSRKGWHMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGITLHYSSLS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  839 TVLWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYgsRPNAPYCWMAWEPSLG 918
Cdd:cd15998   84 TLLWMGVKARVLHKELTWRAPPPQEGDPALPTPRPMLRFYLIAGGIPLIICGITAAVNIHNY--RDHSPYCWLVWRPSLG 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  919 AFYGPASFITFVNCMYFLSIFIQLKRHPErkyelkepteeqqrlaanengeinHQDSMSLSLISTSALENEHTFhsqllg 998
Cdd:cd15998  162 AFYIPVALILLVTWIYFLCAGLHLRGPSA------------------------DGDSVYSPGVQLGALVTTHFL------ 211

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 59823631  999 asltlllYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAWiMTCCP 1063
Cdd:cd15998  212 -------YLAMWACGALAVSQRWLPRVVCSCLYGVAASALGLFVFTHHCARRRDVRASW-RACCP 268
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
 791-1057 1.20e-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: 153.88  E-value: 1.20e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  791 SLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKRcqdpdeppPP 870
Cdd:cd15040   34 KRKPTKILLNLCLALLLANLLFLFGINSTDNPVLCTAVAALLHYFLLASFMWMLVEALLLYLRLVKVFGT--------YP 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  871 PRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNapYCWMAWE-PSLGAFYGPASFITFVNCMYFLSIFIQLKRHP-ER 948
Cdd:cd15040  106 RHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSG--YCWLSNGnGLYYAFLGPVLLIILVNLVIFVLVLRKLLRLSaKR 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  949 KYELKEPTEEQQRLAAnengeinhqdSMSLSLISTsalenehtfhsqllgasltlllyvalWMFGALAVSlyyPLDLVFS 1028
Cdd:cd15040  184 NKKKRKKTKAQLRAAV----------SLFFLLGLT--------------------------WIFGILAIF---GARVVFQ 224

                        250       260       270
                 ....*....|....*....|....*....|
gi 59823631 1029 FVFGATSlSFSAFFV-VHHCVNREDVRLAW 1057
Cdd:cd15040  225 YLFAIFN-SLQGFFIfIFHCLRNKEVRKAW 253
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
 781-1057 3.93e-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: 120.78  E-value: 3.93e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  781 YIYHHSLIRISlksWHMLVNLCFHIFLTCVVFVGGITQTRNAS--ICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKa 858
Cdd:cd13952   26 YLLFPKLRNLR---GKILINLCLSLLLAQLLFLIGQLLTSSDRpvLCKALAILLHYFLLASFFWMLVEAFDLYRTFVKV- 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  859 krcqdpdEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNA--PYCWM-AWEPSLGAFYGPASFITFVNCMYF 935
Cdd:cd13952  102 -------FGSSERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYggEYCWLsNGNALLWAFYGPVLLILLVNLVFF 174

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  936 LSIFIQLKRHPERKYELKEPTEEQQRLAAnengeinhqdsmSLSLIstsalenehtfhsqllgasltlllyVAL---WMF 1012
Cdd:cd13952  175 ILTVRILLRKLRETPKQSERKSDRKQLRA------------YLKLF-------------------------PLMgltWIF 217

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 59823631 1013 GALAVslYYPLDLVFSFVFGATSlSFSAFFV-VHHCVNREDVRLAW 1057
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 ...
 796-1062 3.19e-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: 97.71  E-value: 3.19e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  796 HMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVT--KKAKRCQdpdeppppprp 873
Cdd:cd15441   38 SIHKNLVACLLLAELLFLLGINQTENLFPCKLIAILLHYFYLSAFSWLLVESLHLYRMLTepRDINHGH----------- 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  874 MLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWM-AWEPSLGAFYGPASFITFVNCMYF---LSIFIQLKRHPERK 949
Cdd:cd15441  107 MRFYYLLGYGIPAIIVGLSVGLRPDGYG---NPDFCWLsVNETLIWSFAGPIAFVIVITLIIFilaLRASCTLKRHVLEK 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  950 YELKepteeqQRLAANengeinhqdSMSLSLISTSalenehtfhsqllgasltlllyvalWMFGALAVSlyYPLDlVFSF 1029
Cdd:cd15441  184 ASVR------TDLRSS---------FLLLPLLGAT-------------------------WVFGLLAVN--EDSE-LLHY 220

                        250       260       270
                 ....*....|....*....|....*....|...
gi 59823631 1030 VFGATSLSFSAFFVVHHCVNREDVRLAWIMTCC 1062
Cdd:cd15441  221 LFAGLNFLQGLFIFLFYCIFNKKVRRELKNALL 253
LRR_8 pfam13855
Leucine rich repeat;
85-141 7.19e-18

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 78.72  E-value: 7.19e-18
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631     85 TLILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRI 141
Cdd:pfam13855    5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
85-183 6.36e-17

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


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 84.99  E-value: 6.36e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   85 TLILSNNKISELKNgSFSGLSLLERLDLRNNLISSIdPGAFWGLSSLKRLDLTNNRIGCLNADIFrGLTNLVRLNLSGNL 164
Cdd:COG4886  140 ELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPEPLG-NLTNLEELDLSGNQ 216

                         90
                 ....*....|....*....
gi 59823631  165 FSSLSQGtfdyLASLRSLE 183
Cdd:COG4886  217 LTDLPEP----LANLTNLE 231
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
 800-954 7.38e-17

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: 81.93  E-value: 7.38e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYK---QVTKKAKRcqdpdeppppprPMLR 876
Cdd:cd15440   42 NLCLCLLIAEIVFLLGIDQTENRTLCGVIAGLLHYFFLAAFSWMLLEGFQLYVmlvEVFEPEKS------------RIKW 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  877 FYLIGGGIPIIVCGITAAANIKNYGSRpnaPYCWMAWE-PSLGAFYGPASFITFVNCMyFLSIFIQLK-RHPERKYELKE 954
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 ...
 796-1057 1.10e-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: 81.22  E-value: 1.10e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  796 HMlvNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdePPPPPRPML 875
Cdd:cd15933   40 HK--NLCVALLLAQILLLAGEWAEGNKVACKVVAILLHFFFMAAFSWMLVEGLHLYLMIVK----------VFNYKSKMR 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  876 RFYLIGGGIPIIVCGITAAANIKNYGSrPNapYCWMA------WepslgAFYGPASFITFVNCMYF---LSIFIQLKRHP 946
Cdd:cd15933  108 YYYFIGWGLPAIIVAISLAILFDDYGS-PN--VCWLSlddgliW-----AFVGPVIFIITVNTVILilvVKITVSLSTND 179

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  947 ErkyelKEPTEEQQRLAANENGEInhqdsMSLSLISTSalenehtfhsqllgasltlllyvalWMFGALAVSlyyPLDLV 1026
Cdd:cd15933  180 A-----KKSQGTLAQIKSTAKASV-----VLLPILGLT-------------------------WLFGVLVVN---SQTIV 221

                        250       260       270
                 ....*....|....*....|....*....|.
gi 59823631 1027 FSFVFGATSLSFSAFFVVHHCVNREDVRLAW 1057
Cdd:cd15933  222 FQYIFVILNSLQGLMIFLFHCVLNSEVRSAF 252
LRR_8 pfam13855
Leucine rich repeat;
107-165 2.02e-16

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 74.48  E-value: 2.02e-16
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 59823631    107 LERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLF 165
Cdd:pfam13855    3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
 788-1054 3.99e-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: 76.81  E-value: 3.99e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  788 IRISLKSWHMlvNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEP 867
Cdd:cd15991   32 LRSNLHSIHK--NLVAALFFSELIFLIGINQTENPFVCTVVAILLHYFYMSTFAWMFVEGLHIYRMLTE---------VR 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  868 PPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWEPSL-GAFYGPASFITFVNCMYFLsifiqlkrhp 946
Cdd:cd15991  101 NINTGHMRFYYVVGWGIPAIITGLAVGLDPQGYG---NPDFCWLSVQDTLiWSFAGPIGIVVIINTVIFV---------- 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  947 erkYELKEPTEEQQRlaanengeiNHQDSMSLSLISTSALenehtfhsqllgaslTLLLYVALWMFGALAVSlyyPLDLV 1026
Cdd:cd15991  168 ---LAAKASCGRRQR---------YFEKSGVISMLRTAFL---------------LLLLISATWLLGLMAVN---SDTLS 217

                        250       260
                 ....*....|....*....|....*...
gi 59823631 1027 FSFVFGATSLSFSAFFVVHHCVNREDVR 1054
Cdd:cd15991  218 FHYLFAIFSCLQGIFIFFFHCIFNKEVR 245
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 801-936 1.41e-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: 1.41e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  801 LCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTkkakrcQDPDEPPPPPRPMLrfyLI 880
Cdd:cd15438   43 LCLSLFLAHLIFLLGINNTNNQVACAVVAGLLHYFFLAAFCWMSLEGVELYLMVV------QVFNTQSLKKRYLL---LI 113

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631  881 GGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWEPS-LGAFYGPASFITFVNCMYFL 936
Cdd:cd15438  114 GYGVPLVIVAISAAVNSKGYG---TQRHCWLSLERGfLWSFLGPVCLIILVNAIIFV 167
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
76-190 1.57e-13

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


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 74.20  E-value: 1.57e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   76 PDTLPNRT--VTLILSNNKISELkNGSFSGLSLLERLDLRNNLISSIDpgAFWGLSSLKRLDLTNNRIGCLNADIfrGLT 153
Cdd:COG4886  198 PEPLGNLTnlEELDLSGNQLTDL-PEPLANLTNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPPLA--NLT 272

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 59823631  154 NLVRLNLSGNLFSSLSQGTFDYLASLRSLEFQTEYLL 190
Cdd:COG4886  273 NLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLN 309
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
85-182 7.52e-13

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


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 72.27  E-value: 7.52e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   85 TLILSNNKiselkngSFSGLSLLERLDLRNNLISSIdPGAFWGLSSLKRLDLTNNRIGCLNADIFrGLTNLVRLNLSGNL 164
Cdd:COG4886  100 ELDLSGNE-------ELSNLTNLESLDLSGNQLTDL-PEELANLTNLKELDLSNNQLTDLPEPLG-NLTNLKSLDLSNNQ 170

                         90
                 ....*....|....*...
gi 59823631  165 FSSLSQGtFDYLASLRSL 182
Cdd:COG4886  171 LTDLPEE-LGNLTNLKEL 187
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
 782-962 8.25e-13

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: 70.33  E-value: 8.25e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  782 IYHHSLIRiSLKSWH--MLVNLCFHIFLTCVVFV-GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKA 858
Cdd:cd15039   23 LAVYALLP-ELRNLHgkCLMCLVLSLFVAYLLLLiGQLLSSGDSTLCVALGILLHFFFLAAFFWLNVMSFDIWRTFRGKR 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  859 KRCQDPDEPPPpprpmLRFY-LIGGGIPIIVCGITAAANIKN--YGSRPN--APYCWM--AWePSLGAFYGPASFITFVN 931
Cdd:cd15039  102 SSSSRSKERKR-----FLRYsLYAWGVPLLLVAVTIIVDFSPntDSLRPGygEGSCWIsnPW-ALLLYFYGPVALLLLFN 175

                        170       180       190
                 ....*....|....*....|....*....|..
gi 59823631  932 CMYFLSIFIQLKRHP-ERKYELKEPTEEQQRL 962
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 ...
 781-1059 1.22e-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: 69.75  E-value: 1.22e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  781 YIYHHSLIRISLKSWHMlvNLCFHIFLTCVVFV--GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKka 858
Cdd:cd15258   26 YIAFRKLRRDYPSKIHM--NLCAALLLLNLAFLlsSWIASFGSDGLCIAVAVALHYFLLACLTWMGLEAFHLYLLLVK-- 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  859 krcqdpDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYG-----SRPNAPYCWMAWEPSLGAFY----GPASFITF 929
Cdd:cd15258  102 ------VFNTYIRRYILKLCLVGWGLPALLVTLVLSVRSDNYGpitipNGEGFQNDSFCWIRDPVVFYitvvGYFGLTFL 175

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  930 VNCMYFLSIFIQLKRHPERKyELKEPTEEQQRLaanengeinhqdsmsLSLISTSALenehtfhsqllgasltlllyvaL 1009
Cdd:cd15258  176 FNMVMLATVLVQICRLREKA-QATPRKRALHDL---------------LTLLGLTFL----------------------L 217

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 59823631 1010 WMFGALAVSLYYPLDLVFSFVFgATSLSFSAFFV-VHHCVNREDVRLAWIM 1059
Cdd:cd15258  218 GLTWGLAFFAWGPFNLPFLYLF-AIFNSLQGFFIfIWYCSMKENVRKQWRA 267
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
 797-945 1.95e-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: 68.91  E-value: 1.95e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  797 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVtkkakRCQDPDEPPPPPRPMLR 876
Cdd:cd15439   39 LHLQLSLCLFLADLLFLVGIDRTDNKVLCSIIAGFLHYLFLACFAWMFLEAVHLFLTV-----RNLKVVNYFSSHRFKKR 113

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 59823631  877 F-YLIGGGIPIIVCGITAAANIKNYGSRpnaPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 945
Cdd:cd15439  114 FmYPVGYGLPAVIVAISAAVNPQGYGTP---KHCWLSMEKGfIWSFLGPVCVIIVINLVLFCLTLWILREK 181
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
 797-942 2.80e-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: 68.43  E-value: 2.80e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  797 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKrcqdpdepppPPRPMLR 876
Cdd:cd15251   40 ILINFCLSIISSNILILVGQTQTLNKGVCTMTAAFLHFFFLSSFCWVLTEAWQSYMAVTGRMR----------TRLIRKR 109

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 59823631  877 FYLIGGGIPIIVCGITAA-ANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQL 942
Cdd:cd15251  110 FLCLGWGLPALVVAVSVGfTRTKGYGT---SSYCWLSLEGGlLYAFVGPAAAVVLVNMVIGILVFNKL 174
LRR_8 pfam13855
Leucine rich repeat;
129-182 4.50e-12

Leucine rich repeat;


Pssm-ID: 404697 [Multi-domain]  Cd Length: 61  Bit Score: 62.16  E-value: 4.50e-12
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 59823631    129 SSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSSLSQGTFDYLASLRSL 182
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYL 54
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 77-183 7.29e-12

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: 66.35  E-value: 7.29e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   77 DTLPNRTvTLILSNNKISELKNgsFSGLSLLERLDLRNNLISSI---------------------------DPGAFWGLS 129
Cdd:cd21340   43 EFLTNLT-HLYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVVeglenltnleelhienqrlppgekltfDPRSLAALS 119

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 59823631  130 -SLKRLDLTNNRIGCLNAdiFRGLTNLVRLNLSGNLFSSLSQgTFDYLASLRSLE 183
Cdd:cd21340  120 nSLRVLNISGNNIDSLEP--LAPLRNLEQLDASNNQISDLEE-LLDLLSSWPSLR 171
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
 786-1057 9.99e-12

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: 66.87  E-value: 9.99e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  786 SLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpd 865
Cdd:cd15256   31 SVSTIRNQRYHIHANLSFAVLVAQILLLISFRFEPGTLPCKIMAILLHFFFLSAFAWMLVEGLHLYSMVIK--------- 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  866 EPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNapyCWMAWEP-SLGAFYGPASFITFVNcmyfLSIFIQLKR 944
Cdd:cd15256  102 VFGSEESKHFYYYGIGWGSPLLICIISLTSALDSYGESDN---CWLSLENgAIWAFVAPALFVIVVN----IGILIAVTR 174

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  945 HPERkyelkepteeqqrlAANENGEInHQDSMSLSLISTSALENEHTFHSQllgasltlllyvalWMFGALAVSLYyplD 1024
Cdd:cd15256  175 VISR--------------ISADNYKV-HGDANAFKLTAKAVAVLLPILGSS--------------WVFGVLAVNTH---A 222

                        250       260       270
                 ....*....|....*....|....*....|....
gi 59823631 1025 LVFSFVFgATSLSFSAFFV-VHHCVNREDVRLAW 1057
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 ...
 800-1061 1.27e-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: 66.40  E-value: 1.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 879
Cdd:cd15993   42 NIAAALFLSELLFLLGINRTENQFLCTVVAILLHYFFLSTFAWLFVQGLHIYRMQTE---------ARNVNFGAMRFYYA 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  880 IGGGIPIIVCGITAAANIKNYGsrpNAPYCWMA-WEPSLGAFYGPASFITFVNCMYFLsIFIQLKRHPERKYELKEPTEE 958
Cdd:cd15993  113 IGWGVPAIITGLAVGLDPEGYG---NPDFCWISiHDKLVWSFAGPIVVVIVMNGVMFL-LVARMSCSPGQKETKKTSVLM 188

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  959 QQRlaanengeinhqDSMSLSLISTsalenehtfhsqllgasltlllyvALWMFGALAVSLYYpldLVFSFVF-GATSLS 1037
Cdd:cd15993  189 TLR------------SSFLLLLLIS------------------------ATWLFGLLAVNNSV---LAFHYLHaILCCLQ 229

                        250       260
                 ....*....|....*....|....
gi 59823631 1038 FSAFFVVhHCVNREDVRLAWIMTC 1061
Cdd:cd15993  230 GLAVLLL-FCVLNEEVQEAWKLAC 252
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
 800-945 1.72e-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: 66.05  E-value: 1.72e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTkkakrcqdpDEPPPPPRPMLRFYL 879
Cdd:cd15437   42 NLCCSLFLAELIFLIGINMNANKLFCSIIAGLLHYFFLAAFAWMCIEGIHLYLIVV---------GVIYNKGFLHKNFYI 112

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631  880 IGGGIPIIVCGITAAANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 945
Cdd:cd15437  113 FGYGSPAVVVGISAALGYKYYGT---TKVCWLSTENNfIWSFIGPACLIILVNLLAFGVIIYKVFRH 176
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
 796-1043 1.76e-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: 65.76  E-value: 1.76e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    796 HMlvNLCFHIFLTCVVFVGGITQTRNASI--------CQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEP 867
Cdd:pfam00002   40 HL--NLFASFILRALLFLVGDAVLFNKQDldhcswvgCKVVAVFLHYFFLANFFWMLVEGLYLYTLLVE---------VF 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    868 PPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWE-PSLGAFYGPASFITFVNCMYFLSIFIQLKRHp 946
Cdd:pfam00002  109 FSERKYFWWYLLIGWGVPALVVGIWAGVDPKGYG---EDDGCWLSNEnGLWWIIRGPILLIILVNFIIFINIVRILVQK- 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    947 erkyeLKEPTEEQQRLAanengeinhqdSMSLSLISTSALenehtfhsqllgasltlllyVAL----WMFGALAVSLYYP 1022
Cdd:pfam00002  185 -----LRETNMGKSDLK-----------QYRRLAKSTLLL--------------------LPLlgitWVFGLFAFNPENT 228

                          250       260
                   ....*....|....*....|.
gi 59823631   1023 LDLVFSFVFGATSlSFSAFFV 1043
Cdd:pfam00002  229 LRVVFLYLFLILN-SFQGFFV 248
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
 799-935 3.09e-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: 3.09e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  799 VNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVtkkaKRCQDPDEPPPPPRPMLRFY 878
Cdd:cd15931   41 LHLCLCLSMSHTLFLAGIEYVENELACTVMAGLLHYLFLASFVWMLLEALQLHLLV----RRLTKVQVIQRDGLPRPLLC 116

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 59823631  879 LIGGGIPIIVCGITAAANIKNYGsRPNapYCWMAWEPS-LGAFYGPASFITFVNCMYF 935
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 ...
 797-955 1.28e-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: 1.28e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  797 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKrcqdpdepppPPRPMLR 876
Cdd:cd15989   42 ILINFCLSIISSNILILVGQTQTHNKGICTMTTAFLHFFFLASFCWVLTEAWQSYMAVTGKIR----------TRLIRKR 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  877 FYLIGGGIPIIVCGITAA-ANIKNYGSRpnaPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQL--------KRHP 946
Cdd:cd15989  112 FLCLGWGLPALVVAISMGfTKAKGYGTP---HYCWLSLEGGlLYAFVGPAAAVVLVNMVIGILVFNKLvsrdgildKKLK 188


                 ....*....
gi 59823631  947 ERKYELKEP 955
Cdd:cd15989  189 HRAGQMSEP 197
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
 800-945 2.64e-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: 62.52  E-value: 2.64e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 879
Cdd:cd15252   42 NLCISLFLAELVFLIGINTTTNKIFCSVIAGLLHYFFLAAFAWMFIEGIQLYLMLVE---------VFENEGSRHKNFYI 112

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631  880 IGGGIPIIVCGITAAANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 945
Cdd:cd15252  113 FGYGSPAVIVGVSAALGYRYYGT---TKVCWLSTENYfIWSFIGPATLIILLNLIFLGVAIYKMFRH 176
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
 797-942 4.91e-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: 4.91e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  797 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKrcqdpdepppPPRPMLR 876
Cdd:cd15988   40 ILLNFCLSILASNILILVGQSQTLSKGVCTMTAAFLHFFFLSSFCWVLTEAWQSYLAVIGRMR----------TRLVRKR 109

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 59823631  877 FYLIGGGIPIIVCGITAA-ANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQL 942
Cdd:cd15988  110 FLCLGWGLPALVVAVSVGfTRTKGYGT---ASYCWLSLEGGlLYAFVGPAAVIVLVNMLIGIIVFNKL 174
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
 800-936 7.58e-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: 7.58e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdePPPPPRPMLRFYL 879
Cdd:cd16007   42 NLCINLFLAELLFLIGIDKTQYQIACPIFAGLLHFFFLAAFSWLCLEGVQLYLMLVE----------VFESEYSRKKYYY 111

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 59823631  880 IGGGI-PIIVCGITAAANIKNYGSRPNapyCWMAWEPS-LGAFYGPASFITFVNCMYFL 936
Cdd:cd16007  112 LCGYCfPALVVGISAAIDYRSYGTEKA---CWLRVDNYfIWSFIGPVSFVIVVNLVFLM 167
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
85-170 1.42e-09

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


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 61.87  E-value: 1.42e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   85 TLILSNNKISELKngSFSGLSLLERLDLRNNLISSIDPGAfwGLSSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNL 164
Cdd:COG4886  232 TLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLL 307


                 ....*.
gi 59823631  165 FSSLSQ 170
Cdd:COG4886  308 LNLLEL 313
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
 797-942 3.66e-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: 59.23  E-value: 3.66e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  797 MLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKRcqdpdeppppPRPMLR 876
Cdd:cd15990   43 ILINFCLSIISSNALILIGQTQTRNKVVCTLVAAFLHFFFLSSFCWVLTEAWQSYMAVTGRLRN----------RIIRKR 112

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 59823631  877 FYLIGGGIPIIVCGITAA-ANIKNYGSrpnAPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQL 942
Cdd:cd15990  113 FLCLGWGLPALVVAISVGfTKAKGYGT---VNYCWLSLEGGlLYAFVGPAAAVVLVNMVIGILVFNKL 177
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
 800-937 6.36e-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: 6.36e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 879
Cdd:cd15992   42 NGATALFLSELVFILGINQADNPFACTVIAILLHFFYLCTFSWLFLEGLHIYRMLSE---------VRDINYGPMRFYYL 112

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  880 IGGGIPIIVCGITAAANIKNYGsrpNAPYCWMAWEPSL-GAFYGPASFITFVNC-MYFLS 937
Cdd:cd15992  113 IGWGVPAFITGLAVGLDPEGYG---NPDFCWLSIYDTLiWSFAGPVAFAVSMNVfLYILS 169
PCC TIGR00864
polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) ...
 135-236 6.86e-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: 6.86e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    135 DLTNNRIGCLNADIFRGLTNLVRLNLSGNLFSslsqgtfdylaslrslefqteyllCDCNILWMHRWVKEKNITVRD--- 211
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFE------------------------CDCGLARLPRWAEEKGVKVRQpea 56

                           90       100
                   ....*....|....*....|....*
gi 59823631    212 TRCVYPKSLQAQPVTGVKQELLTCD 236
Cdd:TIGR00864   57 ALCAGPGALAGQPLLGIPLLDSGCD 81
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
 800-945 7.76e-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: 7.76e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 879
Cdd:cd16006   42 NLCINLFIAEFIFLIGIDKTEYKIACPIFAGLLHFFFLAAFAWMCLEGVQLYLMLVE---------VFESEYSRKKYYYV 112

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631  880 IGGGIPIIVCGITAAANIKNYGSRPNapyCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 945
Cdd:cd16006  113 AGYLFPATVVGVSAAIDYKSYGTEKA---CWLRVDNYfIWSFIGPVTFIILLNLIFLVITLCKMVKH 176
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
 797-1057 1.51e-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: 57.53  E-value: 1.51e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  797 MLVNLCFHIFLTCVVFV--GGITQTRNA-SICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRP 873
Cdd:cd15444   40 ILIQLCVALLLLNLVFLldSWIALYKDIvGLCISVAVFLHYFLLVSFTWMGLEAFHMYLALVK--------VFNTYIRKY 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  874 MLRFYLIGGGIPIIVCGITAAANIKNYG-----SRPNAP---YCWMAWEPslgAFY----GPASFITFVNCMYFLSIFIQ 941
Cdd:cd15444  112 ILKFCIVGWGVPAVVVAIVLAVSKDNYGlgsygKSPNGStddFCWINNNI---VFYitvvGYFCVIFLLNISMFIVVLVQ 188

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  942 LKRhperkyelkepTEEQQRLAANENGEInhQDSMSLSLIstsalenehTFhsqllgasltlllyvALWMFGALAVSLYY 1021
Cdd:cd15444  189 LCR-----------IKKQKQLGAQRKTSL--QDLRSVAGI---------TF---------------LLGITWGFAFFAWG 231

                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 59823631 1022 PLDLVFSFVFgATSLSFSAFFV-VHHCVNREDVRLAW 1057
Cdd:cd15444  232 PVNLAFMYLF-AIFNTLQGFFIfIFYCVAKENVRKQW 267
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
 797-1059 2.62e-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: 56.59  E-value: 2.62e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  797 MLVNLCFHIFLTCVVFV--GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRPM 874
Cdd:cd15997   40 ILINLCTALLMLNLVFLlnSWLSSFNNYGLCITVAAFLHYFLLASFTWMGLEAVHMYFALVK--------VFNIYIPNYI 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  875 LRFYLIGGGIPIIVCGITAAANIKNYGS-------RPNAPYCWMAwepSLGAFY----GPASFITFVNCMYFLSIFIQLk 943
Cdd:cd15997  112 LKFCIAGWGIPAVVVALVLAINKDFYGNelssdslHPSTPFCWIQ---DDVVFYisvvAYFCLIFLCNISMFITVLIQI- 187

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  944 rhpeRKYELKEPTEEQQRlaanengeinhqdSMSLSLISTSALenehTFhsqllgasltlllYVAL-WMFGALAvslYYP 1022
Cdd:cd15997  188 ----RSMKAKKPSRNWKQ-------------GFLHDLKSVASL----TF-------------LLGLtWGFAFFA---WGP 230

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 59823631 1023 LDLVFSFVFgATSLSFSAFFV-VHHCVNREDVRLAWIM 1059
Cdd:cd15997  231 VRIFFLYLF-SICNTLQGFFIfVFHCLMKENVRKQWRI 267
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
 800-945 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 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpdEPPPPPRPMLRFYL 879
Cdd:cd15436   42 NLCINLFIAELLFLIGINRTQYTIACPIFAGLLHFFFLAAFCWLCLEGVQLYLLLVE---------VFESEYSRRKYFYL 112

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631  880 IGGGIPIIVCGITAAANIKNYGSRpnaPYCWMAWEPS-LGAFYGPASFITFVNCMYFLSIFIQLKRH 945
Cdd:cd15436  113 CGYSFPALVVAVSAAIDYRSYGTE---KACWLRVDNYfIWSFIGPVTFVITLNLVFLVITLHKMVSH 176
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
 800-935 1.78e-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: 54.18  E-value: 1.78e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  800 NLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKKAKRCQDPDEPpppprpmlrFYL 879
Cdd:cd16005   42 NLCISLFVAELLFLIGINRTDQPIACAVFAALLHFFFLAAFTWMFLEGVQLYIMLVEVFESEHSRRKY---------FYL 112

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631  880 IGGGIPIIVCGITAAANIKNYGSRpnaPYCWMAWEPS-LGAFYGPASFITFVNCMYF 935
Cdd:cd16005  113 VGYGMPALIVAVSAAVDYRSYGTD---KVCWLRLDTYfIWSFIGPATLIIMLNVIFL 166
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
 784-940 1.93e-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: 54.49  E-value: 1.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  784 HHSLIRISLKSWhMLVNLCFHIFLTCVVFVGGITQTRN-------------------------ASICQAVGIILHYSTLA 838
Cdd:cd15257   28 HTRKLRKSSVTW-VLLNLCSSLLLFNIIFTSGVENTNNdyeistvpdretntvllseeyvepdTDVCTAVAALLHYFLLV 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  839 TVLWVGVTARNIYKQVTKKAKrcqdpdepPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAP-------YCWM 911
Cdd:cd15257  107 TFMWNAVYSAQLYLLLIRMMK--------PLPEMFILQASAIGWGIPAVVVAITLGATYRFPTSLPVFTrtyrqeeFCWL 178

                        170       180       190
                 ....*....|....*....|....*....|.
gi 59823631  912 AWEPSLGAFYGPA--SFITFVNCMYFLSIFI 940
Cdd:cd15257  179 AALDKNFDIKKPLlwGFLLPVGLILITNVIL 209
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 65-141 6.31e-07

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: 51.71  E-value: 6.31e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   65 CSSL-EL---AQVLPPD-----------TLPNRTVTLILSNNKISELKngSFSGLSLLERLDLRNNLISSIDP--GAFWG 127
Cdd:cd21340   89 LTNLeELhieNQRLPPGekltfdprslaALSNSLRVLNISGNNIDSLE--PLAPLRNLEQLDASNNQISDLEEllDLLSS 166

                         90
                 ....*....|....
gi 59823631  128 LSSLKRLDLTNNRI 141
Cdd:cd21340  167 WPSLRELDLTGNPV 180
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
 704-743 5.64e-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: 5.64e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 59823631    704 WDFDLlNGQGGWKSDGCHILYSDENITTIQCYSLSNYAVL 743
Cdd:pfam01825    6 WDFTN-STTGRWSTEGCTTVSLNDTHTVCSCNHLTSFAVL 44
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
 796-953 1.18e-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: 48.67  E-value: 1.18e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  796 HMlvNLCFHIFLTCVVFVGG--ITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRP 873
Cdd:cd15995   41 HM--NLLLAIFLLDTSFLISepLALTGSEAACRAGGMFLHFSLLACLTWMGIEGYNLYRLVVE--------VFNTYVPHF 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  874 MLRFYLIGGGIPIIVCGITAAANIKNYG-----------SRPNAPYCWMAwEPSLGAF--YGPASFITFVNCMYFLSIFI 940
Cdd:cd15995  111 LLKLCAVGWGLPIFLVTLIFLVDQDNYGpiilavhrspeKVTYATICWIT-DSLISNItnLGLFSLVFLFNMAMLATMVV 189

                        170
                 ....*....|...
gi 59823631  941 QLKRHPERKYELK 953
Cdd:cd15995  190 EILRLRPRTHKWS 202
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
 797-1057 2.64e-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: 47.57  E-value: 2.64e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  797 MLVNLCFHIFLTCVVFV--GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRPM 874
Cdd:cd15996   40 ILMNLSTALLFLNLVFLldGWIASFEIDELCITVAVLLHFFLLATFTWMGLEAIHMYIALVK--------VFNTYIRRYI 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  875 LRFYLIGGGIPIIVCGITAAANIKNYG---------SRPNAPYCWMAwEPSLgaFY----GPASFITFVNCMYFLSIFIQ 941
Cdd:cd15996  112 LKFCIIGWGLPALIVSIVLASTNDNYGygyygkdkdGQGGDEFCWIK-NPVV--FYvtcaAYFGIMFLMNVAMFIVVMVQ 188

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  942 L-KRHPER-KYELKEPTEEQQRlaanengeinhqdsmslSLISTSALenehtfhsqllgasltlllyvaLWMFGALAVSL 1019
Cdd:cd15996  189 IcGRNGKRsNRTLREEILRNLR-----------------SVVSLTFL----------------------LGMTWGFAFFA 229

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 59823631 1020 YYPLDLVFSFVFGATSLSFSAFFVVHHCVNREDVRLAW 1057
Cdd:cd15996  230 WGPVNLAFMYLFTIFNSLQGLFIFVFHCALKENVQKQW 267
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
 703-746 2.66e-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: 2.66e-05
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....
gi 59823631     703 RWDFDllngQGGWKSDGCHILYSDENITTIQCYSLSNYAVLMDL 746
Cdd:smart00303    7 FWDES----SGEWSTRGCELLETNGTHTTCSCNHLTTFAVLMDV 46
LRR_4 pfam12799
Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a ...
 107-146 4.16e-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: 4.16e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 59823631    107 LERLDLRNNLISSIDPgaFWGLSSLKRLDLT-NNRIGCLNA 146
Cdd:pfam12799    3 LEVLDLSNNQITDIPP--LAKLPNLETLDLSgNNKITDLSD 41
LRR_RI cd00116
Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 ...
 70-182 4.49e-05

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: 46.96  E-value: 4.49e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   70 LAQVLPPdtLPNRTVTLILSNNKISelkNGS-------FSGLSLLERLDLRNNLISsiDPG------AFWGLSSLKRLDL 136
Cdd:cd00116  128 LAKGLKD--LPPALEKLVLGRNRLE---GAScealakaLRANRDLKELNLANNGIG--DAGiralaeGLKANCNLEVLDL 200

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 59823631  137 TNNRIGCLN----ADIFRGLTNLVRLNLSGNLFSS-----LSQGTFDYLASLRSL 182
Cdd:cd00116  201 NNNGLTDEGasalAETLASLKSLEVLNLGDNNLTDagaaaLASALLSPNISLLTL 255
LRR_RI cd00116
Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 ...
 84-166 4.57e-05

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: 46.96  E-value: 4.57e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   84 VTLILSNNKISElKNGS-----FSGLSLLERLDLRNNLISS-----IDPGAFWGLSSLKRLDLTNNRIGCLNA-DIFRGL 152
Cdd:cd00116  196 EVLDLNNNGLTD-EGASalaetLASLKSLEVLNLGDNNLTDagaaaLASALLSPNISLLTLSLSCNDITDDGAkDLAEVL 274

                         90
                 ....*....|....*..
gi 59823631  153 TN---LVRLNLSGNLFS 166
Cdd:cd00116  275 AEkesLLELDLRGNKFG 291
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
 363-416 8.83e-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: 8.83e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 59823631    363 WPRTLAGITAYLQCTRNTHGSgiypgnpQDERKAWRRCDRGGFWAD---DDYSRCQY 416
Cdd:pfam02793   14 WPRTPAGETVEVPCPDYFSGF-------DPRGNASRNCTEDGTWSEhppSNYSNCTS 63
LRRCT smart00082
Leucine rich repeat C-terminal domain;
189-223 9.73e-05

Leucine rich repeat C-terminal domain;


Pssm-ID: 214507 [Multi-domain]  Cd Length: 51  Bit Score: 41.26  E-value: 9.73e-05
                            10        20        30
                    ....*....|....*....|....*....|....*..
gi 59823631     189 LLCDCNILWMHRWVKEKNITVR--DTRCVYPKSLQAQ 223
Cdd:smart00082    3 FICDCELRWLLRWLQANEHLQDpvDLRCASPSSLRGP 39
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
 799-940 1.10e-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: 45.56  E-value: 1.10e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  799 VNLCFHIFLTCVVFV--GGITQTRNASICQAVGIILHYSTLATVLWVGVTARNIYKQVTKkakrcqdpDEPPPPPRPMLR 876
Cdd:cd15442   46 VNLSSSLLLLNLAFLlnSGVSSRAHPGLCKALGGVTHYFLLCCFTWMAIEAFHLYLLAIK--------VFNTYIHHYFAK 117

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  877 FYLIGGGIPIIVCGITAAAN------IKNYGSRPNAPYCWMAwEPSLGAFYgpasfITfvNCMYFLSIFI 940
Cdd:cd15442  118 LCLVGWGFPALVVTITGSINsygaytIMDMANRTTLHLCWIN-SKHLTVHY-----IT--VCGYFGLTFL 179
PPP1R42 cd21340
protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 ...
 86-183 1.51e-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: 44.78  E-value: 1.51e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631   86 LILSNNKISELKNgsFSGLSLLERLDLRNNLISSIDpgafwGLSSLKRL---DLTNNRIGCLnaDIFRGLTNLVRLNLSG 162
Cdd:cd21340    7 LYLNDKNITKIDN--LSLCKNLKVLYLYDNKITKIE-----NLEFLTNLthlYLQNNQIEKI--ENLENLVNLKKLYLGG 77

                         90       100
                 ....*....|....*....|.
gi 59823631  163 NLFSSLSQgtfdyLASLRSLE 183
Cdd:cd21340   78 NRISVVEG-----LENLTNLE 93
LRR_5 pfam13306
BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich ...
 82-180 2.57e-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: 2.57e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631     82 RTVTLilsNNKISELKNGSFSGlSLLERLDLRNNlISSIDPGAFWGLSSLKRLDLTNNrIGCLNADIFRGlTNLVRLNLS 161
Cdd:pfam13306   37 KSITL---PSSLTSIGSYAFYN-CSLTSITIPSS-LTSIGEYAFSNCSNLKSITLPSN-LTSIGSYAFSN-CSLKSITIP 109

                           90
                   ....*....|....*....
gi 59823631    162 GNLfSSLSQGTFDYLASLR 180
Cdd:pfam13306  110 SSV-TTIGSYAFSNCSNLK 127
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 81-186 3.51e-04

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 45.22  E-value: 3.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    81 NRTVTLILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGA-FWGLSSLKRLDLTNNRigcLNADIFRG-LTNLVRL 158
Cdd:PLN00113   69 SRVVSIDLSGKNISGKISSAIFRLPYIQTINLSNNQLSGPIPDDiFTTSSSLRYLNLSNNN---FTGSIPRGsIPNLETL 145

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 59823631   159 NLSGNLFSS---LSQGTFD------------------YLASLRSLEFQT 186
Cdd:PLN00113  146 DLSNNMLSGeipNDIGSFSslkvldlggnvlvgkipnSLTNLTSLEFLT 194
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
 798-944 4.33e-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: 43.84  E-value: 4.33e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  798 LVNLCFHIFLTCVVFVGGI---TQTRNASICQAVGIILHYSTLATVLWVGVTA-----RNIY--KQVTKKAkrcqdpdep 867
Cdd:cd15932   46 LVNIALSLLIADIWFIIGAaisTPPNPSPACTAATFFIHFFYLALFFWMLTLGlllfyRLVLvfHDMSKST--------- 116

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  868 pppprPMLRFYLIGGGIPIIVCGITAAANIKNYG-SRPNApyCWMAWEPS--LGAFYGPASFITFVNCMYFLSIFIQLKR 944
Cdd:cd15932  117 -----MMAIAFSLGYGCPLIIAIITVAATAPQGGyTRKGV--CWLNWDKTkaLLAFVIPALAIVVVNFIILIVVIFKLLR 189
LRR_4 pfam12799
Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a ...
 130-163 4.45e-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: 4.45e-04
                           10        20        30
                   ....*....|....*....|....*....|....
gi 59823631    130 SLKRLDLTNNRIGCLnaDIFRGLTNLVRLNLSGN 163
Cdd:pfam12799    2 NLEVLDLSNNQITDI--PPLAKLPNLETLDLSGN 33
LRR_4 pfam12799
Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a ...
 85-122 4.96e-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: 4.96e-04
                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 59823631     85 TLILSNNKISELknGSFSGLSLLERLDL-RNNLISSIDP 122
Cdd:pfam12799    5 VLDLSNNQITDI--PPLAKLPNLETLDLsGNNKITDLSD 41
LRR_5 pfam13306
BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich ...
 85-184 6.48e-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: 40.99  E-value: 6.48e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631     85 TLILSNNkISELKNGSFSGLSLLERLDLRNNLIsSIDPGAFWGlSSLKRLDLTNN--RIGcLNAdiFRGLTNLVRLNLSG 162
Cdd:pfam13306   15 SITIPSS-LTSIGEYAFSNCTSLKSITLPSSLT-SIGSYAFYN-CSLTSITIPSSltSIG-EYA--FSNCSNLKSITLPS 88

                           90       100
                   ....*....|....*....|..
gi 59823631    163 NLfSSLSQGTFdYLASLRSLEF 184
Cdd:pfam13306   89 NL-TSIGSYAF-SNCSLKSITI 108
HormR smart00008
Domain present in hormone receptors;
363-416 6.92e-04

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 39.42  E-value: 6.92e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*.
gi 59823631     363 WPRTLAGITAYLQCTRNThgSGIYPGNpqderKAWRRCDRGGFWA--DDDYSRCQY 416
Cdd:smart00008   15 WPQTPAGQLVEVPCPKYF--SGFSYKT-----GASRNCTENGGWSppFPNYSNCTS 63
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
 788-933 7.36e-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: 43.03  E-value: 7.36e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  788 IRIslkswHM-------LVNLCFHIFLTCVVFVGGITQtRNASICQAVGIILHYSTLATVLWV---GVTARNIYKQVTKK 857
Cdd:cd15260   37 ITI-----HMnlfisfaLNNLLWIVWYKLVVDNPEVLL-ENPIWCQALHVLLQYFMVCNYFWMfceGLYLHTVLVVAFIS 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631  858 AKRCqdpdeppppprpMLRFYLIGGGIPIIVCGITAAAnikNYGSRPNAPYCWMAWEPSLGAFYGP------ASFITFVN 931
Cdd:cd15260  111 EKSL------------MRWFIAIGWGVPLVITAIYAGV---RASLPDDTERCWMEESSYQWILIVPvvlsllINLIFLIN 175


                 ..
gi 59823631  932 CM 933
Cdd:cd15260  176 IV 177
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 66-158 2.89e-03

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 42.14  E-value: 2.89e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    66 SSLELAQVLPPD--TLPNRTVTLILSNNKIS-ELKNGSfsgLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNrig 142
Cdd:PLN00113  101 SNNQLSGPIPDDifTTSSSLRYLNLSNNNFTgSIPRGS---IPNLETLDLSNNMLSGEIPNDIGSFSSLKVLDLGGN--- 174

                          90
                  ....*....|....*.
gi 59823631   143 CLNADIFRGLTNLVRL 158
Cdd:PLN00113  175 VLVGKIPNSLTNLTSL 190
LRR smart00370
Leucine-rich repeats, outliers;
104-127 3.88e-03

Leucine-rich repeats, outliers;


Pssm-ID: 197688 [Multi-domain]  Cd Length: 24  Bit Score: 35.79  E-value: 3.88e-03
                            10        20
                    ....*....|....*....|....
gi 59823631     104 LSLLERLDLRNNLISSIDPGAFWG 127
Cdd:smart00370    1 LPNLRELDLSNNQLSSLPPGAFQG 24
LRR_TYP smart00369
Leucine-rich repeats, typical (most populated) subfamily;
104-127 3.88e-03

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


Pssm-ID: 197687 [Multi-domain]  Cd Length: 24  Bit Score: 35.79  E-value: 3.88e-03
                            10        20
                    ....*....|....*....|....
gi 59823631     104 LSLLERLDLRNNLISSIDPGAFWG 127
Cdd:smart00369    1 LPNLRELDLSNNQLSSLPPGAFQG 24
IG_like smart00410
Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.
 249-341 3.99e-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: 3.99e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631     249 SHRQVVFEGDSLPFQCMASYiDQDMQVLWYQDGriVETDESQGIFVEKNMIHNCSLiasalTISNIQAGSTGNWGCHVQT 328
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASG-SPPPEVTWYKQG--GKLLAESGRFSVSRSGSTSTL-----TISNVTPEDSGTYTCAATN 72

                            90
                    ....*....|...
gi 59823631     329 KRGNNTRTVDIVV 341
Cdd:smart00410   73 SSGSASSGTTLTV 85
Ig_3 pfam13927
Immunoglobulin domain; This family contains immunoglobulin-like domains.
 242-326 5.38e-03

Immunoglobulin domain; This family contains immunoglobulin-like domains.


Pssm-ID: 464046 [Multi-domain]  Cd Length: 78  Bit Score: 37.16  E-value: 5.38e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    242 PSFYMTPSHrQVVFEGDSLPFQCMASYIDQDmQVLWYQDGRIVETDESQGIFVEKNMihncsliaSALTISNIQAGSTGN 321
Cdd:pfam13927    2 PVITVSPSS-VTVREGETVTLTCEATGSPPP-TITWYKNGEPISSGSTRSRSLSGSN--------STLTISNVTRSDAGT 71


                   ....*
gi 59823631    322 WGCHV 326
Cdd:pfam13927   72 YTCVA 76
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
 90-183 6.85e-03

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 40.99  E-value: 6.85e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631    90 NNKISELKNgSFSGLSLLERLDL-RNNLISSIdPGAFWGLSSLKRLDLTNNRI-GCLNADIFrGLTNLVRLNLSGNlfsS 167
Cdd:PLN00113  222 NNLSGEIPY-EIGGLTSLNHLDLvYNNLTGPI-PSSLGNLKNLQYLFLYQNKLsGPIPPSIF-SLQKLISLDLSDN---S 295

                          90
                  ....*....|....*.
gi 59823631   168 LSQGTFDYLASLRSLE 183
Cdd:PLN00113  296 LSGEIPELVIQLQNLE 311
PLN03150 PLN03150
hypothetical protein; Provisional
 102-166 8.04e-03

hypothetical protein; Provisional


Pssm-ID: 178695 [Multi-domain]  Cd Length: 623  Bit Score: 40.57  E-value: 8.04e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 59823631   102 SGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNRIGCLNADIFRGLTNLVRLNLSGNLFS 166
Cdd:PLN03150  439 SKLRHLQSINLSGNSIRGNIPPSLGSITSLEVLDLSYNSFNGSIPESLGQLTSLRILNLNGNSLS 503
LRR_5 pfam13306
BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich ...
 94-195 8.93e-03

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: 37.91  E-value: 8.93e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 59823631     94 SELKNGSFSGLSLLErLDLRNNLISsIDPGAFWGLSSLKRLDLTNNrIGCLNADIFRGlTNLVRLNLSGNLfSSLSQGTF 173
Cdd:pfam13306    1 TSIGSYAFYNCSLTS-ITIPSSLTS-IGEYAFSNCTSLKSITLPSS-LTSIGSYAFYN-CSLTSITIPSSL-TSIGEYAF 75

                           90       100
                   ....*....|....*....|....*...
gi 59823631    174 DYLASLRSLEFQT------EYLLCDCNI 195
Cdd:pfam13306   76 SNCSNLKSITLPSnltsigSYAFSNCSL 103
 
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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