Rho guanine nucleotide exchange factor 18 Pleckstrin homology (PH) domain; ARHGEF18, also called p114RhoGEF, is a key regulator of RhoA-Rock2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium, and consequently is essential for cellular differentiation, morphology and eventually organ function. ARHGEF18 contains Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  747 QRQLHLEGMLCWKTTSGRLKDILAILLTDVLLLLQEKDQKYVFASVDSKPPVISLQKLIVREVANEEKAMFLISASLQGP 826
Cdd:cd15794     1 RRQLLLEGMLYWKAASGRLKDILALLLTDVLLLLQEKDQKYVFASVDSKPPVISLQKLIVREVANEEKAMFLISASLNGP 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 768001550  827 EMYEIYTSSKEDRNAWMAHIQRAVESCPDEEEGPFSLPE 865
Cdd:cd15794    81 EMYEIHTNSKEDRNTWMAHIRRAVESCPDEEEGLFSEPE 119

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1053 LVQRIQTLSQLLLNLQAVIAHQDSYVETQRAAIQEREK---QFRLQSTRGNLLLEQERQRnfekQREERAALEKLQSQLR 1129
Cdd:COG1196   230 LLLKLRELEAELEELEAELEELEAELEELEAELAELEAeleELRLELEELELELEEAQAE----EYELLAELARLEQDIA 305

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1130 HEQQRWERERQwQHQELERAGARLQEREGEARQLRERLEQERAELERQRQAYQHDLERLREAQRAVERER 1199
Cdd:COG1196   306 RLEERRRELEE-RLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAEL 374

protein kinase C conserved region 1 (C1 domain) superfamily; The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains. It contains the motif HX12CX2CXnCX2CX4HX2CX7C, where C and H are cysteine and histidine, respectively; X represents other residues; and n is either 13 or 14. C1 has a globular fold with two separate Zn(2+)-binding sites. It was originally discovered as lipid-binding modules in protein kinase C (PKC) isoforms. C1 domains that bind and respond to phorbol esters (PE) and diacylglycerol (DAG) are referred to as typical, and those that do not respond to PE and DAG are deemed atypical. A C1 domain may also be referred to as PKC or non-PKC C1, based on the parent protein's activity. Most C1 domain-containing non-PKC proteins act as lipid kinases and scaffolds, except PKD which acts as a protein kinase. PKC C1 domains play roles in membrane translocation and activation of the enzyme.

                          10        20        30
                  ....*....|....*....|....*....|
gi 768001550  361 VNGHQLLQGTFSGPSSCPLCGKPFLSSASL 390
Cdd:cd20876     5 SNGHQFVTGSFSGPTLCVVCDKPVTGKELL 34

Rho guanine nucleotide exchange factor 18 Pleckstrin homology (PH) domain; ARHGEF18, also called p114RhoGEF, is a key regulator of RhoA-Rock2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium, and consequently is essential for cellular differentiation, morphology and eventually organ function. ARHGEF18 contains Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  747 QRQLHLEGMLCWKTTSGRLKDILAILLTDVLLLLQEKDQKYVFASVDSKPPVISLQKLIVREVANEEKAMFLISASLQGP 826
Cdd:cd15794     1 RRQLLLEGMLYWKAASGRLKDILALLLTDVLLLLQEKDQKYVFASVDSKPPVISLQKLIVREVANEEKAMFLISASLNGP 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 768001550  827 EMYEIYTSSKEDRNAWMAHIQRAVESCPDEEEGPFSLPE 865
Cdd:cd15794    81 EMYEIHTNSKEDRNTWMAHIRRAVESCPDEEEGLFSEPE 119

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550    516 VLYELMQTEVHHVRTLKIMLKVYSRALQEELQ-FSSKAIGRLFPCADDLLETHSHFLARLKERRQESLEEGsdrnyviQK 594
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSV-------ER 73

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550    595 IGDLLVQQfsgengERMKEKYGVFCSGHNEAVSHYKLLlQQNKKFQNLIKKIGNFSIVRRLGVQECILLVTQRITKYPVL 674
Cdd:smart00325   74 IGDVFLKL------EEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLL 146

                           170       180       190
                    ....*....|....*....|....*....|....
gi 768001550    675 VERIIQNTEAGTEDYEDLTQALNLIKDIISQVDA 708
Cdd:smart00325  147 LKELLKHTPEDHEDREDLKKALKAIKELANQVNE 180

PH domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550   734 LKNGLTFRKEDMLQRQLHLEGMLCWKTTSGRLKDILAILLTDVLLLLQEKDQKYVFAS-------VDSK--PPVISLQKL 804
Cdd:pfam17838    1 HPLGEEFKKLDLTTRKLIHEGPLTWRNSKGKLVEVHALLLEDILVLLQEKDQKLVLAClstgsenVDQKtqSPIISLKKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 768001550   805 IVREVANEEKAMFLISASLQGPEMYEIYTSSKEDRNAWMAHIQRAVE 851
Cdd:pfam17838   81 IVREVATDKKAFFLISTSPSDPQMYELHASTKSERNTWTKLIQDAIE 127

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  1059 TLSQLLLNLQAVIAHQDSYVETQRAAIQEREKQFRLQSTRGNLLLEQERQRNFEKQREERAALEKLQSQLRHEQQRWERE 1138
Cdd:pfam17380  266 TENEFLNQLLHIVQHQKAVSERQQQEKFEKMEQERLRQEKEEKAREVERRRKLEEAEKARQAEMDRQAAIYAEQERMAME 345

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 768001550  1139 RQwqhQELERagARLQEREGEARQLRErlEQERAELERQRQAYQHDLERLREAQR 1193
Cdd:pfam17380  346 RE---RELER--IRQEERKRELERIRQ--EEIAMEISRMRELERLQMERQQKNER 393

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  1052 ELVQRIQTLSQLLLNLQAVIAHQDSYVETQRAAIQEREKQFRLQSTRGNLLLEQErqrnfEKQREERAALEKLQSQLRHE 1131
Cdd:TIGR02168  341 ELEEKLEELKEELESLEAELEELEAELEELESRLEELEEQLETLRSKVAQLELQI-----ASLNNEIERLEARLERLEDR 415

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 768001550  1132 QQRWERERQWQHQELERA-----GARLQEREGEARQLRERLEQERAELERQRQAYQHDLERLREAQR 1193
Cdd:TIGR02168  416 RERLQQEIEELLKKLEEAelkelQAELEELEEELEELQEELERLEEALEELREELEEAEQALDAAER 482

protein kinase C conserved region 1 (C1 domain) found in 190 kDa guanine nucleotide exchange factor (p190RhoGEF) and similar proteins; p190RhoGEF, also called Rho guanine nucleotide exchange factor (RGNEF), Rho guanine nucleotide exchange factor 28 (ARHGEF28), or RIP2, is a brain-enriched, RhoA-specific guanine nucleotide exchange factor that regulates signaling pathways downstream of integrins and growth factor receptors. It is involved in axonal branching, synapse formation and dendritic morphogenesis, as well as in focal adhesion formation, cell motility and B-lymphocytes activation. In addition to the Dbl homology (DH)-PH domain, p190RhoGEF contains an N-terminal C1 (Protein kinase C conserved region 1) domain. This model corresponds to the C1 domain. The C1 domain is a cysteine-rich zinc binding domain that does not bind DNA nor possess structural similarity to conventional zinc finger domains; it contains two separate Zn(2+)-binding sites.

                          10        20        30
                  ....*....|....*....|....*....|
gi 768001550  361 VNGHQLLQGTFSGPSSCPLCGKPFLSSASL 390
Cdd:cd20876     5 SNGHQFVTGSFSGPTLCVVCDKPVTGKELL 34

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768001550    794 SKPPVISLQKLIVREVAN----EEKAMFLISasLQGPEMYEIYTSSKEDRNAWMAHIQRAV 850
Cdd:smart00233   43 KPKGSIDLSGCTVREAPDpdssKKPHCFEIK--TSDRKTLLLQAESEEEREKWVEALRKAI 101

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550   1101 LLLEQERQRNFEKQREERAalEKLQSQLRHEQQRWERERQwqhqELERAGARLQEregEARQLRER-LEQERAELERQRQ 1179
Cdd:smart00935    9 ILQESPAGKAAQKQLEKEF--KKRQAELEKLEKELQKLKE----KLQKDAATLSE---AAREKKEKeLQKKVQEFQRKQQ 79

                            90
                    ....*....|.
gi 768001550   1180 AYQHDLERLRE 1190
Cdd:smart00935   80 KLQQDLQKRQQ 90

Rho guanine nucleotide exchange factor 18 Pleckstrin homology (PH) domain; ARHGEF18, also called p114RhoGEF, is a key regulator of RhoA-Rock2 signaling that is crucial for maintenance of polarity in the vertebrate retinal epithelium, and consequently is essential for cellular differentiation, morphology and eventually organ function. ARHGEF18 contains Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  747 QRQLHLEGMLCWKTTSGRLKDILAILLTDVLLLLQEKDQKYVFASVDSKPPVISLQKLIVREVANEEKAMFLISASLQGP 826
Cdd:cd15794     1 RRQLLLEGMLYWKAASGRLKDILALLLTDVLLLLQEKDQKYVFASVDSKPPVISLQKLIVREVANEEKAMFLISASLNGP 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 768001550  827 EMYEIYTSSKEDRNAWMAHIQRAVESCPDEEEGPFSLPE 865
Cdd:cd15794    81 EMYEIHTNSKEDRNTWMAHIRRAVESCPDEEEGLFSEPE 119

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550    516 VLYELMQTEVHHVRTLKIMLKVYSRALQEELQ-FSSKAIGRLFPCADDLLETHSHFLARLKERRQESLEEGsdrnyviQK 594
Cdd:smart00325    1 VLKELLQTERNYVRDLKLLVEVFLKPLKKELKlLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSV-------ER 73

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550    595 IGDLLVQQfsgengERMKEKYGVFCSGHNEAVSHYKLLlQQNKKFQNLIKKIGNFSIVRRLGVQECILLVTQRITKYPVL 674
Cdd:smart00325   74 IGDVFLKL------EEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQCRRLTLESLLLKPVQRLTKYPLL 146

                           170       180       190
                    ....*....|....*....|....*....|....
gi 768001550    675 VERIIQNTEAGTEDYEDLTQALNLIKDIISQVDA 708
Cdd:smart00325  147 LKELLKHTPEDHEDREDLKKALKAIKELANQVNE 180

Rho guanine nucleotide exchange factor 2 Pleckstrin homology (PH) domain; ARHGEF2, also called GEF-H1, acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. It is thought to play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. ARHGEF2 contains a C1 domain followed by Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  747 QRQLHLEGMLCWKTTSGRLKDILAILLTDVLLLLQEKDQKYVFASVDsKPPVISLQKLIVREVANEEKAMFLISASlqGP 826
Cdd:cd13393     1 RRKLIHDGCLLWKTASGRFKDVQVLLMTDVLVFLQEKDQKYIFPTLD-KPAVISLQNLIVRDIANQEKGMFLISAA--PP 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 768001550  827 EMYEIYTSSKEDRNAWMAHIQRAVESCPDEEEgpFSLPEEE 867
Cdd:cd13393    78 EMYEVHAASRDDRNTWMRLIQQTVKTCPSREE--FPLIETE 116

rho guanine nucleotide exchange factor; RhoGEFs belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. The members here all contain Dbl homology (DH)-PH domains. In addition some members contain N-terminal C1 (Protein kinase C conserved region 1) domains, PDZ (also called DHR/Dlg homologous regions) domains, ANK (ankyrin) domains, and RGS (Regulator of G-protein signalling) domains or C-terminal ATP-synthase B subunit. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. RhoGEF2/Rho guanine nucleotide exchange factor 2, p114RhoGEF/p114 Rho guanine nucleotide exchange factor, p115RhoGEF, p190RhoGEF, PRG/PDZ Rho guanine nucleotide exchange factor, RhoGEF 11, RhoGEF 12, RhoGEF 18, AKAP13/A-kinase anchoring protein 13, and LARG/Leukemia-associated Rho guanine nucleotide exchange factor are included in this CD. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  750 LHLEGMLCWKTTSGRLKDILAILLTDVLLLLQEKDQKYVFASVDSKPPVISLQKLIVREVANEEKAMFLISASLqgPEMY 829
Cdd:cd15789     1 LKFEGTAWLKQARGKTKDVLVVVLTDVLFFLQEKDQKYVFVSPDNKAGVVSLQKLLVREKAGQEKRMFLISASP--DGMP 78

                          90       100
                  ....*....|....*....|....
gi 768001550  830 EIYTSSKE---DRNAWMAHIQRAV 850
Cdd:cd15789    79 EMYELKVQkpkDKNTWIQTIRQAV 102

A-kinase anchoring protein 13 Pleckstrin homology (PH) domain; The Rho-specific GEF activity of AKAP13 (also called Brx-1, AKAP-Lbc, and proto-Lbc) mediates signaling downstream of G-protein coupled receptors and Toll-like receptor 2. It plays a role in cell growth, cell development and actin fiber formation. Protein kinase A (PKA) binds and phosphorylates AKAP13, regulating its Rho-GEF activity. Alternative splicing of this gene in humans has at least 3 transcript variants encoding different isoforms (i.e. proto-/onco-Lymphoid blast crisis, Lbc and breast cancer nuclear receptor-binding auxiliary protein, Brx) containing a dbl oncogene homology (DH) domain and PH domain which are required for full transforming activity. The DH domain is associated with guanine nucleotide exchange activation while the PH domain has multiple functions including determine protein sub-cellular localisation via phosphoinositide interactions, while others bind protein partners. Other ligands include protein kinase C which is bound by the PH domain of AKAP13, serving to activate protein kinase D and mobilize a cardiac hypertrophy signaling pathway. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  753 EGMLCWKTTSGRLKDILAILLTDVLLLLQEKDQKYVFASVDSKPPVISLQKLIVREVANEEKAMFLISASLQGPEMYEIY 832
Cdd:cd13392     4 DGPVSLKNTAGRLKEVQAVLLSDVLVFLQEKDQKYVFASLDQKSTVISLKKLIVREVAHEEKGLFLISMGIADPEMVEVH 83

                          90       100
                  ....*....|....*....|
gi 768001550  833 TSSKEDRNAWMAHIQRAVES 852
Cdd:cd13392    84 ASSKEERNSWMQIIQDTINT 103

PDZ Rho guanine nucleotide exchange factor Pleckstrin homology (PH) domain; PRG (also called RhoGEF11) belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. RhoGEFs activate Rho GTPases regulating cytoskeletal structure, gene transcription, and cell migration. PRG contains an N-terminal PDZ domain, a regulators of G-protein signaling-like (RGSL) domain, a linker region, and a C-terminal Dbl-homology (DH) and pleckstrin-homology (PH) domains which bind and catalyze the exchange of GDP for GTP on RhoA. As is the case in p115-RhoGEF, it is thought that the PRG activated by relieving autoinhibition caused by the linker region. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  725 KMDLKSSSKLKNGLT--FRKEDMLQRQLHLEGMLCWKTTSGRLKDILAILLTDVLLLLQEKDQKYVF--------ASVDS 794
Cdd:cd13391     1 RLDATALERASNPLAaeFKNLDLTTRRMIHEGPLTWRISKDKTLDLHVLLLEDLLVLLQKQDEKLVLkchsktavGSSDS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 768001550  795 K---PPVISLQKLIVREVANEEKAMFLISASLQGPEMYEIYTSSKEDRNAWMAHIQRAV 850
Cdd:cd13391    81 KqtfSPVLKLNSVLIRSVATDKRALFIICTSKLGPQIYELVALTSSEKNTWMELLEEAV 139

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1053 LVQRIQTLSQLLLNLQAVIAHQDSYVETQRAAIQEREK---QFRLQSTRGNLLLEQERQRnfekQREERAALEKLQSQLR 1129
Cdd:COG1196   230 LLLKLRELEAELEELEAELEELEAELEELEAELAELEAeleELRLELEELELELEEAQAE----EYELLAELARLEQDIA 305

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1130 HEQQRWERERQwQHQELERAGARLQEREGEARQLRERLEQERAELERQRQAYQHDLERLREAQRAVERER 1199
Cdd:COG1196   306 RLEERRRELEE-RLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAEL 374

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1049 LESELVQRIQTLSQlllnlQAVIAHQdsYVEtqraaIQEREKQFRLQSTRGNLLLEQERQRNFEKQREERAA-LEKLQSQ 1127
Cdd:COG1196   194 ILGELERQLEPLER-----QAEKAER--YRE-----LKEELKELEAELLLLKLRELEAELEELEAELEELEAeLEELEAE 261

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1128 LRHEQQRWERERQwqhqELERAGARLQEREGEARQLR---ERLEQERAELERQRQAYQHDLERLREAQRA 1194
Cdd:COG1196   262 LAELEAELEELRL----ELEELELELEEAQAEEYELLaelARLEQDIARLEERRRELEERLEELEEELAE 327

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1049 LESELVQRIQTLSQLLLNLQAVIAHQDSYVETQRAAIQEREKQFRLQSTRGNLLLEQERQRNFEKQREERAALEKLQSQL 1128
Cdd:COG1196   310 RRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELL 389

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768001550 1129 RHEQQrwERERQWQHQELERAGARLQEREGEARQLRERLEQERAELERQRQAYQHDLERLREAQRA 1194
Cdd:COG1196   390 EALRA--AAELAAQLEELEEAEEALLERLERLEEELEELEEALAELEEEEEEEEEALEEAAEEEAE 453

Family of unknown function (DUF5401); This is a family of unknown function found in Chromadorea.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  1059 TLSQLLLNLQAVIAHQDSYVETQRAAIQEREKQFRLQSTRGNLLLEQERQRNFEKQREERAALEKLQSQLRHEQQRWERE 1138
Cdd:pfam17380  266 TENEFLNQLLHIVQHQKAVSERQQQEKFEKMEQERLRQEKEEKAREVERRRKLEEAEKARQAEMDRQAAIYAEQERMAME 345

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 768001550  1139 RQwqhQELERagARLQEREGEARQLRErlEQERAELERQRQAYQHDLERLREAQR 1193
Cdd:pfam17380  346 RE---RELER--IRQEERKRELERIRQ--EEIAMEISRMRELERLQMERQQKNER 393

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1049 LESELVQRIQTLSQLLLNLQAVIAHQDSYVETQRAAIQEREKQFRLQSTRGNLLLEQERQRNFEKQREERAALEKLQSQL 1128
Cdd:COG1196   349 AEEELEEAEAELAEAEEALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLERLERLEEELEELEE 428

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 768001550 1129 RHEQQrwERERQWQHQELERAGARLQEREGEARQLRERLEQERAELERQRQAYQHDLERLREAQ 1192
Cdd:COG1196   429 ALAEL--EEEEEEEEEALEEAAEEEAELEEEEEALLELLAELLEEAALLEAALAELLEELAEAA 490

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1051 SELVQRIQTLSQLLLNLQAVIAHQDSYVETQRAAIQEREKQFRLQS-TRGNLLLEQ------ERQRNFEKQREERAALEK 1123
Cdd:COG4913   634 EALEAELDALQERREALQRLAEYSWDEIDVASAEREIAELEAELERlDASSDDLAAleeqleELEAELEELEEELDELKG 713

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1124 LQSQLRHEQQRWERERQWQHQELERAG--------ARLQEREGEA------RQLRERLEQERAELERQRQAYQHDLERLR 1189
Cdd:COG4913   714 EIGRLEKELEQAEEELDELQDRLEAAEdlarlelrALLEERFAAAlgdaveRELRENLEERIDALRARLNRAEEELERAM 793

                  ..
gi 768001550 1190 EA 1191
Cdd:COG4913   794 RA 795

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  485 DGHEFEAESWSLAVDAAYAKKQKREVVKRQDVLYELMQTEVHHVRTLKIMLKVYSRALQEELQFSSKA----IGRLFPCA 560
Cdd:COG5422   457 DKFDEEKNLWTLSVPKEVWESLPKQEIKRQEAIYEVIYTERDFVKDLEYLRDTWIKPLEESNIIPENArrnfIKHVFANI 536

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550  561 DDLLETHSHFLARLkeRRQESLEEgsdrnyVIQKIGDLLVQQFS--------GENGErmkekYGVFCSGHNEAVshykll 632
Cdd:COG5422   537 NEIYAVNSKLLKAL--TNRQCLSP------IVNGIADIFLDYVPkfepfikyGASQP-----YAKYEFEREKSV------ 597

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 768001550  633 lqqNKKFQNLIKKIGNFSIVRRLGVQECILLVTQRITKYPVLVERIIQNTEAGTEDYEDLTQALNLIKDIISQVD 707
Cdd:COG5422   598 ---NPNFARFDHEVERLDESRKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPDTEDIPKVIDMLREFLSRLN 669

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768001550 1055 QRIQTLSQLLLNLQAVIAHQDSYVETQRAAIQEREKQFRLQSTrgnLLLEQERQRNFEKQREERAALEKLQSQLRHEQQR 1134
Cdd:COG4913   610 AKLAALEAELAELEEELAEAEERLEALEAELDALQERREALQR---LAEYSWDEIDVASAEREIAELEAELERLDASSDD 686

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768001550 1135 WER-ERQWqhQELERAGARLQEREGEARQLRERLEQERAELERQRQAYQHDLERLREAQRA 1194
Cdd:COG4913   687 LAAlEEQL--EELEAELEELEEELDELKGEIGRLEKELEQAEEELDELQDRLEAAEDLARL 745