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Conserved domains on  [gi|281364746|ref|NP_723538|]
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methuselah-like 15, isoform C [Drosophila melanogaster]

Protein Classification

Mth_Ecto and 7tmB3_Methuselah-like domain-containing protein( domain architecture ID 11664634)

Mth_Ecto and 7tmB3_Methuselah-like domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
379-665 3.16e-91

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: 285.66  E-value: 3.16e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 379 DRIRFKMYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRPTSNDDICFLSGFFVYFCLM 458
Cdd:cd15039    1 SSILGILTLIGLIISLVFLLLTLAVYALLPELRNLHGKCLMCLVLSLFVAYLLLLIGQLLSSGDSTLCVALGILLHFFFL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 459 AAFSWMNITSFDIWKTFGStKLKSCEKSDLRRQFIWYSCYGWGLPTLLTGITIAFTKSDILpDAVRPNFGHGRCWFTYDs 538
Cdd:cd15039   81 AAFFWLNVMSFDIWRTFRG-KRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDFSPNT-DSLRPGYGEGSCWISNP- 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 539 fgSASLLFFSGPVGILFIINLVLFVLTMKYCNKVKNEIYKMQSlnsdkpvlkrRFFQDKTRFVMNTKLCFVMGITWLLEI 618
Cdd:cd15039  158 --WALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKVQS----------RLRSDKQRFRLYLKLFVIMGVTWILEI 225
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 281364746 619 VSILFYDHKktFFWTISDSFNVLLGIFVFIIFVFKRRIYNEIMFKFG 665
Cdd:cd15039  226 ISWFVGGSS--VLWYIFDILNGLQGVFIFLIFVCKRRVLRLLKKKIR 270
Mth_Ecto super family cl11637
The ectodomain of Methuselah (Mth); Mth mutants have a 35% increase in average lifespan and ...
247-355 3.34e-04

The ectodomain of Methuselah (Mth); Mth mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage; The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family; Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site.


The actual alignment was detected with superfamily member cd00251:

Pssm-ID: 448329  Cd Length: 176  Bit Score: 41.89  E-value: 3.34e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 247 VRACqemkICQKIPCIRRCCAEGEMYAKGNfstyCkIDGTDFKFEGFQNLNI-----NANFSKPSDFGIVHG---LQCPK 318
Cdd:cd00251   52 LRGC----VCKLKPCIRFCCPHGKIMDNGQ----C-SDTVQEELRYDPYVNItladgSVDLRHVLTEFIVQGdlpLPCES 122
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 281364746 319 -FRLDPDNfPDDSHTINpSNGSLIIHNTFKTYTNTQYC 355
Cdd:cd00251  123 mYELDREN-EFDEWTLF-ENGTLLRHYDSRLLSKQEYC 158
 
Name Accession Description Interval E-value
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
379-665 3.16e-91

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: 285.66  E-value: 3.16e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 379 DRIRFKMYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRPTSNDDICFLSGFFVYFCLM 458
Cdd:cd15039    1 SSILGILTLIGLIISLVFLLLTLAVYALLPELRNLHGKCLMCLVLSLFVAYLLLLIGQLLSSGDSTLCVALGILLHFFFL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 459 AAFSWMNITSFDIWKTFGStKLKSCEKSDLRRQFIWYSCYGWGLPTLLTGITIAFTKSDILpDAVRPNFGHGRCWFTYDs 538
Cdd:cd15039   81 AAFFWLNVMSFDIWRTFRG-KRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDFSPNT-DSLRPGYGEGSCWISNP- 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 539 fgSASLLFFSGPVGILFIINLVLFVLTMKYCNKVKNEIYKMQSlnsdkpvlkrRFFQDKTRFVMNTKLCFVMGITWLLEI 618
Cdd:cd15039  158 --WALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKVQS----------RLRSDKQRFRLYLKLFVIMGVTWILEI 225
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 281364746 619 VSILFYDHKktFFWTISDSFNVLLGIFVFIIFVFKRRIYNEIMFKFG 665
Cdd:cd15039  226 ISWFVGGSS--VLWYIFDILNGLQGVFIFLIFVCKRRVLRLLKKKIR 270
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
385-646 6.73e-14

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: 71.93  E-value: 6.73e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746  385 MYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRPTSNDDI-------CFLSGFFVYFCL 457
Cdd:pfam00002   7 IYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLdhcswvgCKVVAVFLHYFF 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746  458 MAAFSWMNI----TSFDIWKTFGSTklksceksdlRRQFIWYSCYGWGLPTLLTGITIAFTKSDILPDAvrpnfghgRCW 533
Cdd:pfam00002  87 LANFFWMLVeglyLYTLLVEVFFSE----------RKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDD--------GCW 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746  534 ftyDSFGSASLLFFSGPVGILFIINLVLFVLTmkycnkVKNEIYKMQSLNSDKPVLKRRFFQDKTRFVmntkLCFVMGIT 613
Cdd:pfam00002 149 ---LSNENGLWWIIRGPILLIILVNFIIFINI------VRILVQKLRETNMGKSDLKQYRRLAKSTLL----LLPLLGIT 215
                         250       260       270
                  ....*....|....*....|....*....|...
gi 281364746  614 WLLEIVSILFYDHKKTFFWTISDSFNVLLGIFV 646
Cdd:pfam00002 216 WVFGLFAFNPENTLRVVFLYLFLILNSFQGFFV 248
Mth_Ecto cd00251
The ectodomain of Methuselah (Mth); Mth mutants have a 35% increase in average lifespan and ...
247-355 3.34e-04

The ectodomain of Methuselah (Mth); Mth mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage; The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family; Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site.


Pssm-ID: 119403  Cd Length: 176  Bit Score: 41.89  E-value: 3.34e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 247 VRACqemkICQKIPCIRRCCAEGEMYAKGNfstyCkIDGTDFKFEGFQNLNI-----NANFSKPSDFGIVHG---LQCPK 318
Cdd:cd00251   52 LRGC----VCKLKPCIRFCCPHGKIMDNGQ----C-SDTVQEELRYDPYVNItladgSVDLRHVLTEFIVQGdlpLPCES 122
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 281364746 319 -FRLDPDNfPDDSHTINpSNGSLIIHNTFKTYTNTQYC 355
Cdd:cd00251  123 mYELDREN-EFDEWTLF-ENGTLLRHYDSRLLSKQEYC 158
Methuselah_N pfam06652
Methuselah N-terminus; This family represents the N-terminal region of the Drosophila specific ...
247-355 5.78e-03

Methuselah N-terminus; This family represents the N-terminal region of the Drosophila specific Methuselah protein. Drosophila Methuselah (Mth) mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage. The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family. Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site. This family is found in conjunction with pfam00002.


Pssm-ID: 429053  Cd Length: 179  Bit Score: 38.39  E-value: 5.78e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746  247 VRACqemkICQKIPCIRRCCAEGEMYAKGNFStyCKIDGTD--FKFEGFQNLNINANFSKP----SDFgIVH---GLQCP 317
Cdd:pfam06652  52 LRGC----VCKLKPCIRFCCPHGQIYDNGERE--CSDDHEEelTWPDPHLNVTLENGSVVEvhilTDF-VVQrelPLPCD 124
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 281364746  318 -KFRLDPDNfpDDSHTINPSNGSLIIHNTFKTYTNTQYC 355
Cdd:pfam06652 125 eMFSLDKED--NYWQWTLFENGSLLRHFDRVHLSKQEYC 161
 
Name Accession Description Interval E-value
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
379-665 3.16e-91

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: 285.66  E-value: 3.16e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 379 DRIRFKMYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRPTSNDDICFLSGFFVYFCLM 458
Cdd:cd15039    1 SSILGILTLIGLIISLVFLLLTLAVYALLPELRNLHGKCLMCLVLSLFVAYLLLLIGQLLSSGDSTLCVALGILLHFFFL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 459 AAFSWMNITSFDIWKTFGStKLKSCEKSDLRRQFIWYSCYGWGLPTLLTGITIAFTKSDILpDAVRPNFGHGRCWFTYDs 538
Cdd:cd15039   81 AAFFWLNVMSFDIWRTFRG-KRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIVDFSPNT-DSLRPGYGEGSCWISNP- 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 539 fgSASLLFFSGPVGILFIINLVLFVLTMKYCNKVKNEIYKMQSlnsdkpvlkrRFFQDKTRFVMNTKLCFVMGITWLLEI 618
Cdd:cd15039  158 --WALLLYFYGPVALLLLFNIILFILTAIRIRKVKKETAKVQS----------RLRSDKQRFRLYLKLFVIMGVTWILEI 225
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*..
gi 281364746 619 VSILFYDHKktFFWTISDSFNVLLGIFVFIIFVFKRRIYNEIMFKFG 665
Cdd:cd15039  226 ISWFVGGSS--VLWYIFDILNGLQGVFIFLIFVCKRRVLRLLKKKIR 270
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
379-655 1.09e-65

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: 217.85  E-value: 1.09e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 379 DRIRFKMYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRPTSNDDI-CFLSGFFVYFCL 457
Cdd:cd13952    1 DLALSIITYIGCSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLLTSSDRPVlCKALAILLHYFL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 458 MAAFSWMNITSFDIWKTFGSTKLKSCeksdlRRQFIWYSCYGWGLPTLLTGITIAFtksDILPDAVRPNFGHGRCWFtyd 537
Cdd:cd13952   81 LASFFWMLVEAFDLYRTFVKVFGSSE-----RRRFLKYSLYGWGLPLLIVIITAIV---DFSLYGPSPGYGGEYCWL--- 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 538 SFGSASLLFFSGPVGILFIINLVLFVLTMKYCNKVKNEIYKMQSLNSdkpvlkrrffqDKTRFVMNTKLCFVMGITWLLE 617
Cdd:cd13952  150 SNGNALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKS-----------DRKQLRAYLKLFPLMGLTWIFG 218
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 281364746 618 IVSilFYDHKKTFFWTISDSFNVLLGIFVFIIFVFKRR 655
Cdd:cd13952  219 ILA--PFVGGSLVFWYLFDILNSLQGFFIFLIFCLKNK 254
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
388-655 2.17e-30

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: 120.37  E-value: 2.17e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLR-NLPGKILICLVSSLFAAYLGIALGQlRPTSNDDICFLSGFFVYFCLMAAFSWMNI 466
Cdd:cd15040   10 IGCGLSLLGLLLTIITYILFRKLRkRKPTKILLNLCLALLLANLLFLFGI-NSTDNPVLCTAVAALLHYFLLASFMWMLV 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 467 TSFDIWKTFgsTKLkscEKSDLRRQFIWYSCYGWGLPTLLTGITIAFTKSDILPDAvrpnfghGRCWFtydSFGSASLLF 546
Cdd:cd15040   89 EALLLYLRL--VKV---FGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSS-------GYCWL---SNGNGLYYA 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 547 FSGPVGILFIINLVLFVLTMKycnkvknEIYKMqSLNSDKPVLKRRFFQDKTRFVmntkLCFVMGITWLLeivSILFYDH 626
Cdd:cd15040  154 FLGPVLLIILVNLVIFVLVLR-------KLLRL-SAKRNKKKRKKTKAQLRAAVS----LFFLLGLTWIF---GILAIFG 218
                        250       260
                 ....*....|....*....|....*....
gi 281364746 627 KKTFFWTISDSFNVLLGIFVFIIFVFKRR 655
Cdd:cd15040  219 ARVVFQYLFAIFNSLQGFFIFIFHCLRNK 247
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
388-660 1.89e-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: 79.68  E-value: 1.89e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd15933   10 IGCGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILLLAG-EWAEGNKVACKVVAILLHFFFMAAFSWMLVE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIW----KTFGstklkscEKSDLRrqfiWYSCYGWGLPTLLTGITIAFTKSDILpdavrpnfGHGRCWFTYDsfgSAS 543
Cdd:cd15933   89 GLHLYlmivKVFN-------YKSKMR----YYYFIGWGLPAIIVAISLAILFDDYG--------SPNVCWLSLD---DGL 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 544 LLFFSGPVGILFIINLVLFVLTMKycnkvknEIYKMQslNSDKPVLKRRFFQDKTRFVMNTKLCFVMGITWLLEIVSILf 623
Cdd:cd15933  147 IWAFVGPVIFIITVNTVILILVVK-------ITVSLS--TNDAKKSQGTLAQIKSTAKASVVLLPILGLTWLFGVLVVN- 216
                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 281364746 624 ydhKKTFFWtiSDSFNVLLGIFVFIIFVFKRRIYNEI 660
Cdd:cd15933  217 ---SQTIVF--QYIFVILNSLQGLMIFLFHCVLNSEV 248
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
388-650 4.54e-14

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: 72.83  E-value: 4.54e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLR-NLPGKILICLVSSLFAAYLGIAL-GQLRPTSNDDICFLSGFFVYFCLMAAFSWMN 465
Cdd:cd15258   10 VGCGISAIFLAITILTYIAFRKLRrDYPSKIHMNLCAALLLLNLAFLLsSWIASFGSDGLCIAVAVALHYFLLACLTWMG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 466 ITSFDIW----KTFGSTklksceksdLRRQFIWYSCYGWGLPTLLTGITIAFTKSDILP--DAVRPNF-GHGRCWFTYDS 538
Cdd:cd15258   90 LEAFHLYlllvKVFNTY---------IRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPitIPNGEGFqNDSFCWIRDPV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 539 FGSASLLffsGPVGILFIINLVLFVLTMkycnkvkneiYKMQSLNSDKPVLKRRFFQDKTRFVMNtkLCFVMGITWLLEI 618
Cdd:cd15258  161 VFYITVV---GYFGLTFLFNMVMLATVL----------VQICRLREKAQATPRKRALHDLLTLLG--LTFLLGLTWGLAF 225
                        250       260       270
                 ....*....|....*....|....*....|..
gi 281364746 619 VSILFYDHKKTFFWTIsdsFNVLLGIFVFIIF 650
Cdd:cd15258  226 FAWGPFNLPFLYLFAI---FNSLQGFFIFIWY 254
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
385-646 6.73e-14

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: 71.93  E-value: 6.73e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746  385 MYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRPTSNDDI-------CFLSGFFVYFCL 457
Cdd:pfam00002   7 IYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLdhcswvgCKVVAVFLHYFF 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746  458 MAAFSWMNI----TSFDIWKTFGSTklksceksdlRRQFIWYSCYGWGLPTLLTGITIAFTKSDILPDAvrpnfghgRCW 533
Cdd:pfam00002  87 LANFFWMLVeglyLYTLLVEVFFSE----------RKYFWWYLLIGWGVPALVVGIWAGVDPKGYGEDD--------GCW 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746  534 ftyDSFGSASLLFFSGPVGILFIINLVLFVLTmkycnkVKNEIYKMQSLNSDKPVLKRRFFQDKTRFVmntkLCFVMGIT 613
Cdd:pfam00002 149 ---LSNENGLWWIIRGPILLIILVNFIIFINI------VRILVQKLRETNMGKSDLKQYRRLAKSTLL----LLPLLGIT 215
                         250       260       270
                  ....*....|....*....|....*....|...
gi 281364746  614 WLLEIVSILFYDHKKTFFWTISDSFNVLLGIFV 646
Cdd:pfam00002 216 WVFGLFAFNPENTLRVVFLYLFLILNSFQGFFV 248
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
388-648 2.11e-13

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: 71.07  E-value: 2.11e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLR-NLPGKILICLVSSLFAAYLGIAL-GQLRPTSNDDICFLSGFFVYFCLMAAFSWMN 465
Cdd:cd15996   10 IGCGISAIFSAATLLTYIAFEKLRrDYPSKILMNLSTALLFLNLVFLLdGWIASFEIDELCITVAVLLHFFLLATFTWMG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 466 ITSFDIWktfgsTKLKSCEKSDLRRQFIWYSCYGWGLPTLLTGITIAFTKSDIL----PDAVRPNFGHGRCWFTYDsfgs 541
Cdd:cd15996   90 LEAIHMY-----IALVKVFNTYIRRYILKFCIIGWGLPALIVSIVLASTNDNYGygyyGKDKDGQGGDEFCWIKNP---- 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 542 asLLFF---SGPVGILFIINLVLFVLTM-KYC---NKVKNEIYKMQSLNSDKPVLkrrffqdktrfvmntKLCFVMGITW 614
Cdd:cd15996  161 --VVFYvtcAAYFGIMFLMNVAMFIVVMvQICgrnGKRSNRTLREEILRNLRSVV---------------SLTFLLGMTW 223
                        250       260       270
                 ....*....|....*....|....*....|....
gi 281364746 615 LLEIVSILFYDHKKTFFWTIsdsFNVLLGIFVFI 648
Cdd:cd15996  224 GFAFFAWGPVNLAFMYLFTI---FNSLQGLFIFV 254
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
388-652 4.60e-13

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: 70.07  E-value: 4.60e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLR-NLPGKILICLVSSLFAAYLGIALGQ-LRPTSNDDICFLSGFFVYFCLMAAFSWMN 465
Cdd:cd15997   10 LGCGISSIFLGITLVTYLAFEKLRrDYPSKILINLCTALLMLNLVFLLNSwLSSFNNYGLCITVAAFLHYFLLASFTWMG 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 466 ITS----FDIWKTFGSTklksceksdLRRQFIWYSCYGWGLPTLLTGITIAFTKsDILPDAVRPNFGHGR---CWFTYDS 538
Cdd:cd15997   90 LEAvhmyFALVKVFNIY---------IPNYILKFCIAGWGIPAVVVALVLAINK-DFYGNELSSDSLHPStpfCWIQDDV 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 539 FGSASLLFFsgpVGILFIINLVLFVLtmkycnkVKNEIYKMQSlNSDKPVLKRRFFQDKTRFVmntKLCFVMGITWLLEI 618
Cdd:cd15997  160 VFYISVVAY---FCLIFLCNISMFIT-------VLIQIRSMKA-KKPSRNWKQGFLHDLKSVA---SLTFLLGLTWGFAF 225
                        250       260       270
                 ....*....|....*....|....*....|....
gi 281364746 619 VSilfYDHKKTFFWTISDSFNVLLGIFvfiIFVF 652
Cdd:cd15997  226 FA---WGPVRIFFLYLFSICNTLQGFF---IFVF 253
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
388-657 7.79e-13

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: 69.90  E-value: 7.79e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNL-PGKILICLVSSLFAAYLGIALGQLRPTSN------------------------ 442
Cdd:cd15257   10 IGCVLSIAGLVITIIFHLHTRKLRKSsVTWVLLNLCSSLLLFNIIFTSGVENTNNDyeistvpdretntvllseeyvepd 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 443 DDICFLSGFFVYFCLMAAFSWMNITSFDIWktfgsTKLKSCEKSDLRRQFIWYSCYGWGLPTLLTGITIAFTKS--DILP 520
Cdd:cd15257   90 TDVCTAVAALLHYFLLVTFMWNAVYSAQLY-----LLLIRMMKPLPEMFILQASAIGWGIPAVVVAITLGATYRfpTSLP 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 521 DAVRPNFGHGRCWF----TYDSFGSASLLFFSGPVGILFIINLVLFVLTM-KYCNKVKNeiykmqslnsDKPVLKRRFFQ 595
Cdd:cd15257  165 VFTRTYRQEEFCWLaaldKNFDIKKPLLWGFLLPVGLILITNVILFIMTSqKVLKKNNK----------KLTTKKRSYMK 234
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 281364746 596 dktRFVMNTKLCFVMGITWLLEIVSILFYDHKKTFFWTISDSFNVLLGIFVFIIFVFKRRIY 657
Cdd:cd15257  235 ---KIYITVSVAVVFGITWILGYLMLVNNDLSKLVFSYIFCITNTTQGVQIFILYTWRTPEF 293
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
388-652 6.29e-12

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: 66.52  E-value: 6.29e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFL-SGFFVYFCLmAAFSWMNI 466
Cdd:cd15440   10 IGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLCLCLLIAEIVFLLG-IDQTENRTLCGViAGLLHYFFL-AAFSWMLL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 467 TSFDIW----KTFGSTKlksceksdlRRQFiWYSCYGWGLPTLLTGITIAFTksdilpdavrpNFGHG---RCWFTYDSF 539
Cdd:cd15440   88 EGFQLYvmlvEVFEPEK---------SRIK-WYYLFGYGLPALIVAVSAGVD-----------PTGYGtedHCWLSTENG 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 540 gsaSLLFFSGPVGILFIINLVLFVLTMKYCNKVKNEIYKMqslnSDKPVLKRRFFQDKTRFVmntkLCFVMGITWlleIV 619
Cdd:cd15440  147 ---FIWSFVGPVIVVLLANLVFLGMAIYVMCRHSSRSASK----KDASKLKNIRGWLKGSIV----LVVLLGLTW---TF 212
                        250       260       270
                 ....*....|....*....|....*....|...
gi 281364746 620 SILFYDHKKTFFWTISDSFNVLLGIFVFIIFVF 652
Cdd:cd15440  213 GLLFINQESIVMAYIFTILNSLQGLFIFIFHCV 245
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
388-655 1.27e-11

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: 65.35  E-value: 1.27e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAK-LRNLPGKILICLVSSLFAAYLGIALGQLRpTSNDDICFLSGFFVYFCLMAAFSWMnI 466
Cdd:cd15251   10 VGCGVSCLALLTLLAIYAAFWRyIRSERSIILINFCLSIISSNILILVGQTQ-TLNKGVCTMTAAFLHFFFLSSFCWV-L 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 467 TsfDIWKTFGSTKLKsCEKSDLRRQFIwysCYGWGLPTLLTGITIAFTKSDilpdavrpnfGHGRCWFTYDSFGSASLLF 546
Cdd:cd15251   88 T--EAWQSYMAVTGR-MRTRLIRKRFL---CLGWGLPALVVAVSVGFTRTK----------GYGTSSYCWLSLEGGLLYA 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 547 FSGPVGILFIINLVLFVLTM-KYCNKVKNEIYKMQSLNSDKPVLKrrffqdktrfvmntklcfVMGITWLLEIVSILfyD 625
Cdd:cd15251  152 FVGPAAAVVLVNMVIGILVFnKLVSRDGISDNAMASLWSSCVVLP------------------LLALTWMSAVLAMT--D 211
                        250       260       270
                 ....*....|....*....|....*....|
gi 281364746 626 HKKTFFWTISDSFNVLLGIFVFIIFVFKRR 655
Cdd:cd15251  212 RRSVLFQILFAVFDSLQGFVIVMVHCILRR 241
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
388-652 3.32e-11

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: 64.19  E-value: 3.32e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd15441   10 IGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVACLLLAELLFLLG-INQTENLFPCKLIAILLHYFYLSAFSWLLVE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIWKTFGSTKLksceksDLRRQFIWYSCYGWGLPTLLTGITIAftksdilpdaVRPNfGHGR---CWF-TYDSFGSAs 543
Cdd:cd15441   89 SLHLYRMLTEPRD------INHGHMRFYYLLGYGIPAIIVGLSVG----------LRPD-GYGNpdfCWLsVNETLIWS- 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 544 llfFSGPVGILFIINLVLFVLTMKYCNKVKNEIYKMQSLNSDkpvLKRRFFqdktrfvmntkLCFVMGITWLLEIVSIlf 623
Cdd:cd15441  151 ---FAGPIAFVIVITLIIFILALRASCTLKRHVLEKASVRTD---LRSSFL-----------LLPLLGATWVFGLLAV-- 211
                        250       260
                 ....*....|....*....|....*....
gi 281364746 624 YDHKKTFFWTISdSFNVLLGIFVFIIFVF 652
Cdd:cd15441  212 NEDSELLHYLFA-GLNFLQGLFIFLFYCI 239
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
399-648 3.43e-11

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: 64.10  E-value: 3.43e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 399 LTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNITSFDIWKTFgsT 478
Cdd:cd15991   21 ITFILLVLIRTLRSNLHSIHKNLVAALFFSELIFLIG-INQTENPFVCTVVAILLHYFYMSTFAWMFVEGLHIYRML--T 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 479 KLKSCEKSDLRrqfiWYSCYGWGLPTLLTGITIAFTKSdilpdavrpnfGHGRCWFTYDSFGSASLLFFSGPVGILFIIN 558
Cdd:cd15991   98 EVRNINTGHMR----FYYVVGWGIPAIITGLAVGLDPQ-----------GYGNPDFCWLSVQDTLIWSFAGPIGIVVIIN 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 559 LVLFVLTMKYCNKVKNEIYKMQSLNSdkpVLKRRFFqdktrfvmntkLCFVMGITWLLEIVSIlfyDHKKTFFWTISDSF 638
Cdd:cd15991  163 TVIFVLAAKASCGRRQRYFEKSGVIS---MLRTAFL-----------LLLLISATWLLGLMAV---NSDTLSFHYLFAIF 225
                        250
                 ....*....|
gi 281364746 639 NVLLGIFVFI 648
Cdd:cd15991  226 SCLQGIFIFF 235
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
388-650 6.87e-11

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: 63.69  E-value: 6.87e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLR-NLPGKILICLVSSLFAAYLGIALGQLRPTSND--DICFLSGFFVYFCLMAAFSWM 464
Cdd:cd15444   10 IGCGLSAIFLSVTLVTYIAFEKIRrDYPSKILIQLCVALLLLNLVFLLDSWIALYKDivGLCISVAVFLHYFLLVSFTWM 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 465 NITSFDIWktfgsTKLKSCEKSDLRRQFIWYSCYGWGLPTLLTGITIAFTKSDI-------LPDAVRPNFghgrCWFTYD 537
Cdd:cd15444   90 GLEAFHMY-----LALVKVFNTYIRKYILKFCIVGWGVPAVVVAIVLAVSKDNYglgsygkSPNGSTDDF----CWINNN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 538 SFGSASLLffsGPVGILFIINLVLFVLTM-KYCNKVKNEIYKMQSLNSdkpvlkrrfFQDKTRFVmntKLCFVMGITWLL 616
Cdd:cd15444  161 IVFYITVV---GYFCVIFLLNISMFIVVLvQLCRIKKQKQLGAQRKTS---------LQDLRSVA---GITFLLGITWGF 225
                        250       260       270
                 ....*....|....*....|....*....|....
gi 281364746 617 EIVSILFYDHKKTFFWTIsdsFNVLLGIFVFIIF 650
Cdd:cd15444  226 AFFAWGPVNLAFMYLFAI---FNTLQGFFIFIFY 256
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
389-655 7.36e-11

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: 63.16  E-value: 7.36e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 389 GLLISCCFYalTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIAL--GQLRPTSNDDICFLSGFFVYFCLMAAFSWMNI 466
Cdd:cd15259   13 ALCLLCLLA--TIITYIVFHRLIRISRKGRHMLVNLCLHLLLTCVVfvGGINRTANQLVCQAVGILLHYSTLCTLLWVGV 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 467 TSFDIWKTFgSTKLKSCEKSDL----RRQFIWYSCYGWGLPTLLTGITIAFTksdilpdaVRPNFGHGRCWFTYDsfgsA 542
Cdd:cd15259   91 TARNMYKQV-TKTAKPPQDEDQpprpPKPMLRFYLIGWGIPLIICGITAAVN--------LDNYSTYDYCWLAWD----P 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 543 SLLFFSGPVGILFIINLVLFVLTmkYCnKVKneiykmQSLNSdkpvlkrrfFQDKTRFVMNTKLCFVmgITWLLEIVSIL 622
Cdd:cd15259  158 SLGAFYGPAALIVLVNCIYFLRI--YC-QLK------GAPVS---------FQSQLRGAVITLFLYV--AMWACGALAVS 217
                        250       260       270
                 ....*....|....*....|....*....|...
gi 281364746 623 FYDHKKTFFWTISDSFNVLLGIFVFIIFVFKRR 655
Cdd:cd15259  218 QRYFLDLVFSCLYGATCSSLGLFVLIHHCLSRE 250
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
388-649 7.53e-11

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: 63.24  E-value: 7.53e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd15438   10 VGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHLCLSLFLAHLIFLLG-INNTNNQVACAVVAGLLHYFFLAAFCWMSLE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIW----KTFGSTKLKSceksdlrrqfiWYSC-YGWGLPTLLTGITIAFTKSdilpdavrpnfGHGR---CWFTYDSf 539
Cdd:cd15438   89 GVELYlmvvQVFNTQSLKK-----------RYLLlIGYGVPLVIVAISAAVNSK-----------GYGTqrhCWLSLER- 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 540 gsASLLFFSGPVGILFIINLVLFVLTmkycnkVKNEIYKMQSLNSDKPVLKRrffqDKTRFVMNTKLCFVMGITWlleIV 619
Cdd:cd15438  146 --GFLWSFLGPVCLIILVNAIIFVIT------VWKLAEKFSSINPDMEKLRK----IRALTITAIAQLCILGCTW---IF 210
                        250       260       270
                 ....*....|....*....|....*....|
gi 281364746 620 SILFYDHKKTFFWTISDSFNVLLGIFVFII 649
Cdd:cd15438  211 GFFQFSDSTLVMSYLFTILNSLQGLFIFLL 240
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
379-649 1.83e-10

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: 61.97  E-value: 1.83e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 379 DRIRFKMYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRpTSNDDICFLSGFFVYFCLM 458
Cdd:cd15439    1 DLALTVITYVGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQLSLCLFLADLLFLVGIDR-TDNKVLCSIIAGFLHYLFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 459 AAFSWMNITSFDIWKTFgsTKLKSCEKSDLRRQFIWYSC-YGWGLPTLLTGITIAftksdilpdaVRPNfGHG---RCWF 534
Cdd:cd15439   80 ACFAWMFLEAVHLFLTV--RNLKVVNYFSSHRFKKRFMYpVGYGLPAVIVAISAA----------VNPQ-GYGtpkHCWL 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 535 TYDSFGSASllfFSGPVGILFIINLVLFVLTMKYCNKvkneiyKMQSLNSDKPVLKrrffqdktrfvmNTKL-------- 606
Cdd:cd15439  147 SMEKGFIWS---FLGPVCVIIVINLVLFCLTLWILRE------KLSSLNAEVSTLK------------NTRLltfkaiaq 205
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 281364746 607 CFVMGITWLLEIVSILFYDHKKTFFWTIsdsFNVLLGIFVFII 649
Cdd:cd15439  206 LFILGCTWILGLFQVGPVATVMAYLFTI---TNSLQGVFIFLV 245
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
388-661 9.32e-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: 60.35  E-value: 9.32e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAK-LRNLPGKILICLVSSLFAAYLGIALGQLRPTSNDdICFLSGFFVYFCLMAAFSWMnI 466
Cdd:cd15988   10 IGCAVSCMALLILLAIYAAFWRfIRSERSIILLNFCLSILASNILILVGQSQTLSKG-VCTMTAAFLHFFFLSSFCWV-L 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 467 TsfDIWKTFGSTkLKSCEKSDLRRQFIwysCYGWGLPTLLTGITIAFTKSDilpdavrpnfGHGRCWFTYDSFGSASLLF 546
Cdd:cd15988   88 T--EAWQSYLAV-IGRMRTRLVRKRFL---CLGWGLPALVVAVSVGFTRTK----------GYGTASYCWLSLEGGLLYA 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 547 FSGPVGILFIINLVLFVLTMkycNKVK-----NEIYKMQSLNSDKPVLKRRFFQDKTRFVMNTKL--------------- 606
Cdd:cd15988  152 FVGPAAVIVLVNMLIGIIVF---NKLMsrdgiSDKSKKQRAGSEAEPCSSLLLKCSKCGVVSSAAmssatassamaslws 228
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 281364746 607 -CFV---MGITWLLEIVSILfyDHKKTFFWTISDSFNVLLGIFVFIIFVFKRRIYNEIM 661
Cdd:cd15988  229 sCVVlplLALTWMSAVLAMT--DRRSILFQVLFAVFNSVQGFVIITVHCFLRREVQDVV 285
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
392-652 6.50e-09

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: 57.50  E-value: 6.50e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 392 ISCCFYALTLIVYI------SIAKLRNLPgKILICLVSSLFAAYLGIALGQ-LRPTSNDDICFLSGFFVYFCLMAAFSWM 464
Cdd:cd15442   14 VSMVFLIFTIILYFflrftyQKFKSEDAP-KIHVNLSSSLLLLNLAFLLNSgVSSRAHPGLCKALGGVTHYFLLCCFTWM 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 465 NITSFDIW----KTFGSTklksceksdLRRQFIWYSCYGWGLPTLL---TGITIAFTKSDILPDAVRPNFghGRCWFTYD 537
Cdd:cd15442   93 AIEAFHLYllaiKVFNTY---------IHHYFAKLCLVGWGFPALVvtiTGSINSYGAYTIMDMANRTTL--HLCWINSK 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 538 SFgSASLLFFSGPVGILFIINLVLFVLtmkycnkVKNEIYKMQSLNSDKPvlkrrffQDKTRFVMNTKL---CFVmGITW 614
Cdd:cd15442  162 HL-TVHYITVCGYFGLTFLFNTVVLGL-------VAWKIFHLQSATAGKE-------KCQAWKGGLTVLglsCLL-GVTW 225
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 281364746 615 LLEIVSILFYDHKKTFFWTIsdsFNVLLGIFVFIIFVF 652
Cdd:cd15442  226 GLAFFTYGSMSVPTVYIFAL---LNSLQGLFIFIWFVI 260
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
388-655 9.21e-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: 56.92  E-value: 9.21e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTL----IVYISIAK-LRNLPGKILICLVSSLFAAYLGIALGQLRpTSNDDICFLSGFFVYFCLMAAFS 462
Cdd:cd15990    9 VTLIVGCGVSSLTLllliIIYVSVWRyIRSERSVILINFCLSIISSNALILIGQTQ-TRNKVVCTLVAAFLHFFFLSSFC 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 463 WMNITSfdiWKTFGSTKlKSCEKSDLRRQFIwysCYGWGLPTLLTGITIAFTKSDilpdavrpnfGHGRCWFTYDSFGSA 542
Cdd:cd15990   88 WVLTEA---WQSYMAVT-GRLRNRIIRKRFL---CLGWGLPALVVAISVGFTKAK----------GYGTVNYCWLSLEGG 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 543 SLLFFSGPVGILFIINLVLFVLtmkycnkVKNEIYKMQSLNSDKpvLKRRffqDKTRFVMNTKLCFVMGITWLLEIVSIL 622
Cdd:cd15990  151 LLYAFVGPAAAVVLVNMVIGIL-------VFNKLVSKDGITDKK--LKER---AGASLWSSCVVLPLLALTWMSAVLAIT 218
                        250       260       270
                 ....*....|....*....|....*....|...
gi 281364746 623 fyDHKKTFFWTISDSFNVLLGIFVFIIFVFKRR 655
Cdd:cd15990  219 --DRRSALFQILFAVFDSLEGFVIVMVHCILRR 249
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
388-659 1.66e-08

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: 56.08  E-value: 1.66e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd16007   10 VGIVISLVCLAICISTFCFLRGLQTDRNTIHKNLCINLFLAELLFLIG-IDKTQYQIACPIFAGLLHFFFLAAFSWLCLE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIWktfgsTKLKSCEKSDLRRQFIWYSCyGWGLPTLLTGITIAFTksdilpdaVRPNFGHGRCWFTYDSFGSASllfF 547
Cdd:cd16007   89 GVQLY-----LMLVEVFESEYSRKKYYYLC-GYCFPALVVGISAAID--------YRSYGTEKACWLRVDNYFIWS---F 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 548 SGPVGILFIINLVLFVLTMkycnkvkneiYKMQSLNSDKPVLKRRFFQDKTRFVMNTKLCFVMGITWLLeivSILFYDHK 627
Cdd:cd16007  152 IGPVSFVIVVNLVFLMVTL----------HKMIRSSSVLKPDSSRLDNIKSWALGAITLLFLLGLTWAF---GLLFINKE 218
                        250       260       270
                 ....*....|....*....|....*....|...
gi 281364746 628 KTFFWTISDSFNVLLGIFVFIIF-VFKRRIYNE 659
Cdd:cd16007  219 SVVMAYLFTTFNAFQGMFIFIFHcALQKKVHKE 251
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
388-564 2.20e-08

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: 56.23  E-value: 2.20e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAK-LRNLPGKILICLVSSLFAAYLGIALGQLRpTSNDDICFLSGFFVYFCLMAAFSWMNI 466
Cdd:cd15989   12 VGCGLSCLALITLAVVYAALWRyIRSERSIILINFCLSIISSNILILVGQTQ-THNKGICTMTTAFLHFFFLASFCWVLT 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 467 TSfdiWKTFGSTKLKsCEKSDLRRQFIwysCYGWGLPTLLTGITIAFTKSDilpdavrpnfGHGRCWFTYDSFGSASLLF 546
Cdd:cd15989   91 EA---WQSYMAVTGK-IRTRLIRKRFL---CLGWGLPALVVAISMGFTKAK----------GYGTPHYCWLSLEGGLLYA 153
                        170
                 ....*....|....*...
gi 281364746 547 FSGPVGILFIINLVLFVL 564
Cdd:cd15989  154 FVGPAAAVVLVNMVIGIL 171
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
388-659 3.33e-08

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR144 is an orphan receptor that belongs to the group V adhesion-GPCRs together with GPR133. 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: 320383 [Multi-domain]  Cd Length: 263  Bit Score: 55.24  E-value: 3.33e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRPTsNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd15255   10 IGCGVSLCALIVTFILFLAVGVPKSERTTVHKNLIFALAAAEFLLMFSEWAKG-NQVACWAVTALLHLFFLAAFSWMLVE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIWktfgsTKLKSCEKSDLRRQFIWYSCyGWGLPTLLTGITIAFTKSDILPDavrpnfghGRCWFtydSFGSASLLFF 547
Cdd:cd15255   89 GLLLW-----SKVVAVNMSEDRRMKFYYVT-GWGLPVVIVAVTLATSFNKYVAD--------QHCWL---NVQTDIIWAF 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 548 SGPVGILFIIN-LVLFVLTMKYCNKVKNEiYKMQSLNSD--KPVLKRRFFQDKTRFVmntkLCFVMGITWLLEIVSilfy 624
Cdd:cd15255  152 VGPVLFVLTVNtFVLFRVVMVTVSSARRR-AKMLTPSSDleKQIGIQIWATAKPVLV----LLPVLGLTWLCGVLV---- 222
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 281364746 625 dHKKTFFWTISDSFNVLLGIFVFIIFVfkrrIYNE 659
Cdd:cd15255  223 -HLSDVWAYVFITLNSFQGLYIFLVYA----IYNS 252
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
388-649 3.79e-08

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: 55.21  E-value: 3.79e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLgIALGQLRPTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd15931   10 VGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSMSHT-LFLAGIEYVENELACTVMAGLLHYLFLASFVWMLLE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIWKTFGS-TKLKSCEKSDLRRQfiWYSCYGWGLPTLLTGITIAftksdILPDAvrpnFG-HGRCWFtydSFGSASLL 545
Cdd:cd15931   89 ALQLHLLVRRlTKVQVIQRDGLPRP--LLCLIGYGVPFLIVGVSAL-----VYSDG----YGeAKMCWL---SQERGFNW 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 546 FFSGPVGILFIINLVLFVLTMKYCNKvkneiyKMQSLNSDKPVLKrrffqdKTRFVMNTKLC--FVMGITWLLEIVSIlf 623
Cdd:cd15931  155 SFLGPVIAIIGINWILFCATLWCLRQ------TLSNMNSDISQLK------DTRLLTFKAVAqlFILGCTWVLGLFQT-- 220
                        250       260
                 ....*....|....*....|....*.
gi 281364746 624 yDHKKTFFWTISDSFNVLLGIFVFII 649
Cdd:cd15931  221 -NPVALVFQYLFTILNSLQGAFLFLV 245
7tmE_cAMP_R_Slime_mold cd14940
slime mold cyclic AMP receptor, member of the class E family of seven-transmembrane G ...
391-586 1.54e-07

slime mold cyclic AMP receptor, member of the class E family of seven-transmembrane G protein-coupled receptors; This family represents the class E of seven-transmembrane G-protein coupled receptors found in soil-living amoebas, commonly referred to as slime molds. The class E family includes cAMP receptors (cAR1-4) and cAMP receptors-like proteins (CrlA-C) from Dictyostelium discoideum, and their highly homologous cAMP receptors (TasA and TasB) from Polysphondylium pallidum. So far, four subtypes of cAMP receptors (cAR1-4) have been identified that play an essential role in the detection and transmit of the periodic extracellular cAMP waves that regulate chemotactic cell movement during Dictyostelium development, from the unicellular amoeba aggregate into many multicellular slugs and then differentiate into a sporocarp, a fruiting body with cells specialized for different functions. These four subtypes differ in their expression levels and patterns during development. cAR1 is high-affinity receptor that is the first one to be expressed highly during early aggregation and continues to be expressed at low levels during later developmental stages. cAR1 detects extracellular cAMP and is coupled to G-alpha2 protein. Cells lacking cAR1 fail to aggregate, demonstrating that cAR1 is responsible for aggregation. During later aggregation the high-affinity cAR3 receptor is expressed at low levels. Nonetheless, cells lacking cAR3 do not show an obviously altered pattern of development and are still able to aggregate into fruiting bodies. In contrast, cAR2 and cAR4 are low affinity receptors expressed predominantly after aggregation in pre-stalk cells. cAR2 is essential for normal tip formation and deletion of the receptor arrests development at the mound stage. On the other hand, CAR4 regulates axial patterning and cellular differentiation, and deletion of the receptor results in defects during culmination. Furthermore, three cAMP receptor-like proteins (CrlA-C) were identified in Dictyostelium that show limited sequence similarity to the cAMP receptors. Of these CrlA is thought to be required for normal cell growth and tip formation in developing aggregates.


Pssm-ID: 320094 [Multi-domain]  Cd Length: 256  Bit Score: 53.12  E-value: 1.54e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 391 LISCCFyalTLIVYISIAKLRNLPGKILICL-VSSLFAAYLGIALGQLRPTSNDDI-CFLSGFFVYFCLMAAFSWMNITS 468
Cdd:cd14940   14 IIGCLF---VLVGFWLLKLLRNHITRVISCFcLTSLLKDIIYTMLTLTQSARPDGFlCYLYAIVITYGSLSCWLWTLCLA 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 469 FDIWKTFGSTKlkscekSDLRRQFIWYSCYGWGLPTLLTGITIAFtksdilpDAVRPnfGHGRCWFTYDSFGSASLLFFs 548
Cdd:cd14940   91 ISIYLLIVKRE------PEPEKFEKYYHFVCWGLPLISTIIMLIK-------HHYGP--VGNWCWIGNQYTGYRFGLFY- 154
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 281364746 549 GPVGILFIINLVLFVLTMKYCNKVkneIYKMQSLNSDK 586
Cdd:cd14940  155 GPFFIIFGISAVLVGLTSHYTYQV---IHNWVSDNKDL 189
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
388-659 1.14e-05

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: 47.50  E-value: 1.14e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd15252   10 VGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNLCISLFLAELVFLIG-INTTTNKIFCSVIAGLLHYFFLAAFAWMFIE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIWKTFgstkLKSCEKSDLRRQfiWYSCYGWGLPTLLTGITIAFTKSDILPDAVrpnfghgrCWFTYDSFGSASllfF 547
Cdd:cd15252   89 GIQLYLML----VEVFENEGSRHK--NFYIFGYGSPAVIVGVSAALGYRYYGTTKV--------CWLSTENYFIWS---F 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 548 SGPVGILFIINLVLFVLTmkycnkvkneIYKMQSLNSDKPVLKRRFFQDKTRFVMNTKLCFVMGITWlleIVSILFYDHK 627
Cdd:cd15252  152 IGPATLIILLNLIFLGVA----------IYKMFRHTAGLKPEVSCLENIRSWARGAIALLFLLGLTW---IFGVLHINHA 218
                        250       260       270
                 ....*....|....*....|....*....|...
gi 281364746 628 KTFFWTISDSFNVLLGIFVFIIF-VFKRRIYNE 659
Cdd:cd15252  219 SVVMAYLFTVSNSLQGMFIFLFHcVLSRKVRKE 251
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
388-648 1.38e-05

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: 47.22  E-value: 1.38e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd16006   10 VGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNLCINLFIAEFIFLIG-IDKTEYKIACPIFAGLLHFFFLAAFAWMCLE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIWKTFgstkLKSCEKSDLRRQFIWYScyGWGLPTLLTGITIAFTKSdilpdavrpNFGHGR-CWFTYDSFgsaSLLF 546
Cdd:cd16006   89 GVQLYLML----VEVFESEYSRKKYYYVA--GYLFPATVVGVSAAIDYK---------SYGTEKaCWLRVDNY---FIWS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 547 FSGPVGILFIINLVLFVLTMkyCNKVKNEiykmQSLNSDKPVLKRRFFQDKTRFVMntkLCfVMGITWLLeivSILFYDH 626
Cdd:cd16006  151 FIGPVTFIILLNLIFLVITL--CKMVKHS----NTLKPDSSRLENIKSWVLGAFAL---LC-LLGLTWSF---GLLFINE 217
                        250       260
                 ....*....|....*....|..
gi 281364746 627 KKTFFWTISDSFNVLLGIFVFI 648
Cdd:cd16006  218 ETIVMAYLFTIFNAFQGMFIFI 239
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
388-648 1.44e-05

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: 47.31  E-value: 1.44e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKL--RNLPGKIL-ICLVS---SLFAA----YLGIALGqlRPTSNDDICFLSGFFVYFCL 457
Cdd:cd15932   10 VGLGISILSLVLCLIIEALVWKSvtKNKTSYMRhVCLVNialSLLIAdiwfIIGAAIS--TPPNPSPACTAATFFIHFFY 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 458 MAAFSWMNITSFDIwktFGSTKLKSCEKSDLRRQFIWYsCYGWGLPTLLTGITIAFTKsdilpdavrPNFGHGR---CWF 534
Cdd:cd15932   88 LALFFWMLTLGLLL---FYRLVLVFHDMSKSTMMAIAF-SLGYGCPLIIAIITVAATA---------PQGGYTRkgvCWL 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 535 TYDsfGSASLLFFSGPVGILFIINLVLFVLTmkycnkvkneIYKMQSlnsdKPVLKRRFFQDKTRFVMNTK----LCFVM 610
Cdd:cd15932  155 NWD--KTKALLAFVIPALAIVVVNFIILIVV----------IFKLLR----PSVGERPSKDEKNALVQIGKsvaiLTPLL 218
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 281364746 611 GITWLLEIVSILfyDHKKTFFWTISDSFNVLLGIFVFI 648
Cdd:cd15932  219 GLTWGFGLGTMI--DPKSLAFHIIFAILNSFQGFFILV 254
7tmB2_GPR125 cd15999
G protein-coupled receptor 125, member of the class B2 family of seven-transmembrane G ...
421-563 1.64e-05

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: 47.55  E-value: 1.64e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 421 LVSSLFAAYLGIA--LGQLRPTSNDDICFLSGFFVYFCLMAAFSWMNITSFDIWKTFgSTKLKSCEKSD----LRRQFIW 494
Cdd:cd15999   43 LVNLCFHIFLTCAvfVGGINQTRNASVCQAVGIILHYSTLATVLWVGVTARNIYKQV-TRKAKRCQDPDepppPPRPMLR 121
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 281364746 495 YSCYGWGLPTLLTGITIAftkSDILPDAVRPNFGHgrCWFTYDSfgsaSLLFFSGPVGILFIINLVLFV 563
Cdd:cd15999  122 FYLIGGGIPIIVCGITAA---ANIKNYGSRPNAPY--CWMAWEP----SLGAFYGPAGFIIFVNCMYFL 181
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
390-621 1.76e-05

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: 46.76  E-value: 1.76e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 390 LLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRpTSNDDICFLSGFFVYFCLMAAFSWMNITSF 469
Cdd:cd15993   12 VSASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELLFLLGINR-TENQFLCTVVAILLHYFFLSTFAWLFVQGL 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 470 DIWKTfgSTKLKSCEKSDLRrqfiWYSCYGWGLPTLLTGITIAFTKSdilpdavrpnfGHGRCWFTYDSFGSASLLFFSG 549
Cdd:cd15993   91 HIYRM--QTEARNVNFGAMR----FYYAIGWGVPAIITGLAVGLDPE-----------GYGNPDFCWISIHDKLVWSFAG 153
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 281364746 550 PVGILFIINLVLFVLTMKY-CNKVKNEIYKMQSLNSdkpvLKRRFFqdktrfvmntkLCFVMGITWLLEIVSI 621
Cdd:cd15993  154 PIVVVIVMNGVMFLLVARMsCSPGQKETKKTSVLMT----LRSSFL-----------LLLLISATWLFGLLAV 211
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
388-649 1.85e-05

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: 46.71  E-value: 1.85e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRpTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd15436   10 VGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLCINLFIAELLFLIGINR-TQYTIACPIFAGLLHFFFLAAFCWLCLE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIWktfgsTKLKSCEKSDLRRQFIWYSCyGWGLPTLLTGITIAFTKSDILPDAVrpnfghgrCWFTYDSFGSASllfF 547
Cdd:cd15436   89 GVQLY-----LLLVEVFESEYSRRKYFYLC-GYSFPALVVAVSAAIDYRSYGTEKA--------CWLRVDNYFIWS---F 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 548 SGPVGILFIINLVLFVLTMkycnkvkneiYKMQSLNSDKPVLKRRFFQDKTRFVMNTKLCFVMGITWLLeivSILFYDHK 627
Cdd:cd15436  152 IGPVTFVITLNLVFLVITL----------HKMVSHSDLLKPDSSRLDNIKSWALGAIALLFLLGLTWSF---GLMFINEE 218
                        250       260
                 ....*....|....*....|..
gi 281364746 628 KTFFWTISDSFNVLLGIFVFII 649
Cdd:cd15436  219 SVVMAYLFTIFNAFQGVFIFIF 240
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
435-563 7.13e-05

pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PACAP-R1) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and vasoactive intestinal peptide (VIP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. PACAP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level.


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 45.34  E-value: 7.13e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 435 GQLRPTSNDDICFLSGF-------FVYFCLMAAFSWMNITSFDIWKTFGSTKLKSceksdlRRQFIWYSCYGWGLPTLLT 507
Cdd:cd15987   59 GVLYAEQDSDHCFVSTVeckavmvFFHYCVMSNYFWLFIEGLYLFTLLVETFFPE------RRYFYWYTIIGWGTPTICV 132
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 281364746 508 GITIaftksdilpdAVRPNFGHGRCWFTYDSfgSASLLFFSGPVGILFIINLVLFV 563
Cdd:cd15987  133 TVWA----------VLRLHFDDTGCWDMNDN--TALWWVIKGPVVGSIMINFVLFI 176
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
396-651 9.73e-05

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: 44.81  E-value: 9.73e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 396 FYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNITSFDIWKTF 475
Cdd:cd15992   18 FLLLTFLFLLCLRALRSNKTSIRKNGATALFLSELVFILG-INQADNPFACTVIAILLHFFYLCTFSWLFLEGLHIYRML 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 476 gsTKLKSCEKSDLRrqfiWYSCYGWGLPTLLTGITIAFTksdilPDAV-RPNFghgrCWFT-YDSFgsasLLFFSGPVGI 553
Cdd:cd15992   97 --SEVRDINYGPMR----FYYLIGWGVPAFITGLAVGLD-----PEGYgNPDF----CWLSiYDTL----IWSFAGPVAF 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 554 LFIINLVLFVLTMKYCNKVKNeiykmQSLNSDKPvlkrRFFQDKTRFVMntklCFVMGITWLLEIVSIlfyDHKKTFFWT 633
Cdd:cd15992  158 AVSMNVFLYILSSRASCSAQQ-----QSFEKKKG----PVSGLRTAFTV----LLLVSVTCLLALLSV---NSDVILFHY 221
                        250
                 ....*....|....*...
gi 281364746 634 ISDSFNVLLGIFVFIIFV 651
Cdd:cd15992  222 LFAGFNCLQGPFIFLSHV 239
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
446-655 1.21e-04

orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR114 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 GPR56, GPR64, GPR97, GPR112, and GPR126. 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: 320559 [Multi-domain]  Cd Length: 268  Bit Score: 44.36  E-value: 1.21e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 446 CFLSGFFVYFCLMAAFSWMNITSFDIWKTFGSTKlksceKSDLRRQFIWYSCYGWGLPTLLTGITIAFTKSDILPDAVRP 525
Cdd:cd15443   70 CRAAAALLHYSLLCCLTWMAIEGFHLYLLLVKVY-----NIYIRRYVLKLCVLGWGLPALIVLLVLIFKREAYGPHTIPT 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 526 NFGH---GRCWFTYDSFGSaslLFFSGPVGILFIINLVLFVLTMKYcnkvkneiykMQSLNSDKPVLKRRFFQDktrFVM 602
Cdd:cd15443  145 GTGYqnaSMCWITSSKVHY---VLVLGYAGLTSLFNLVVLAWVVRM----------LRRLRSRKQELGERARRD---WVT 208
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 281364746 603 NTKLCFVMGITWLLEIVSILFYDHKKTFFWTIsdsFNVLLGIFVFIIFVFKRR 655
Cdd:cd15443  209 VLGLTCLLGTTWALAFFSFGVFLIPQLFLFTI---INSLYGFFICLWYCTQRR 258
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
446-563 1.39e-04

secretin receptor-like group of hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group represents G protein-coupled receptors for structurally similar peptide hormones that include secretin, growth-hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide (VIP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Secretin, a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion. Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptors, which are expressed in the brain, pancreas, stomach, kidney, and liver. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. All B1 subfamily GPCRs are able to increase intracellular cAMP levels by coupling to adenylate cyclase via a stimulatory Gs protein. However, depending on its cellular location, some members of subfamily B1 are also capable of coupling to additional G proteins such as G(i/o) and/or G(q) proteins, thereby leading to activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320596 [Multi-domain]  Cd Length: 268  Bit Score: 44.34  E-value: 1.39e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 446 CFLSGFFVYFCLMAAFSWMNITSFdiwktFGSTKLKSCEKSDlRRQFIWYSCYGWGLPTLLTGITIaftksdilpdAVRP 525
Cdd:cd15930   77 CKASMVFFQYCVMANFFWLLVEGL-----YLHTLLVISFFSE-RRYFWWYVLIGWGAPTVFVTVWI----------VARL 140
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 281364746 526 NFGHGRCWFTYDSfgSASLLFFSGPVGILFIINLVLFV 563
Cdd:cd15930  141 YFEDTGCWDINDE--SPYWWIIKGPILISILVNFVLFI 176
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
385-566 2.35e-04

insect diuretic hormone receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors that specifically bind to insect diuretic hormones found in Manduca sexta (moth) and Acheta domesticus (the house cricket), among others. Insect diuretic hormone and their GPCRs play critical roles in the regulation of water and ion balance. Thus they are attractive targets for developing new insecticides. Activation of the diuretic hormone receptors stimulate adenylate cyclase, thereby increasing cAMP levels in Malpighian tube. 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 Gs family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx.


Pssm-ID: 320391 [Multi-domain]  Cd Length: 272  Bit Score: 43.51  E-value: 2.35e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 385 MYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAY----LGIALGQLRPTSNDDICFLSGFFVYFCLmAA 460
Cdd:cd15263    7 IYFIGYSLSLVALSLALWIFLYFKDLRCLRNTIHTNLMFTYILADltwiLTLTLQVSIGEDQKSCIILVVLLHYFHL-TN 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 461 FSWMNITSFDIW----KTFGSTKLKsceksdlrrqFIWYSCYGWGLPTLLTgITIAFTKSDI--LPDAVRPNFGH-GRC- 532
Cdd:cd15263   86 FFWMFVEGLYLYmlvvETFSGENIK----------LRVYAFIGWGIPAVVI-VIWAIVKALAptAPNTALDPNGLlKHCp 154
                        170       180       190
                 ....*....|....*....|....*....|....
gi 281364746 533 WFTYDSFGsaslLFFSGPVGILFIINLVLFVLTM 566
Cdd:cd15263  155 WMAEHIVD----WIFQGPAILVLAVNLVFLVRIM 184
Mth_Ecto cd00251
The ectodomain of Methuselah (Mth); Mth mutants have a 35% increase in average lifespan and ...
247-355 3.34e-04

The ectodomain of Methuselah (Mth); Mth mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage; The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family; Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site.


Pssm-ID: 119403  Cd Length: 176  Bit Score: 41.89  E-value: 3.34e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 247 VRACqemkICQKIPCIRRCCAEGEMYAKGNfstyCkIDGTDFKFEGFQNLNI-----NANFSKPSDFGIVHG---LQCPK 318
Cdd:cd00251   52 LRGC----VCKLKPCIRFCCPHGKIMDNGQ----C-SDTVQEELRYDPYVNItladgSVDLRHVLTEFIVQGdlpLPCES 122
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 281364746 319 -FRLDPDNfPDDSHTINpSNGSLIIHNTFKTYTNTQYC 355
Cdd:cd00251  123 mYELDREN-EFDEWTLF-ENGTLLRHYDSRLLSKQEYC 158
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
388-664 5.03e-04

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: 42.56  E-value: 5.03e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 388 IGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGqLRPTSNDDICFLSGFFVYFCLMAAFSWMNIT 467
Cdd:cd15437   10 LGIIISLICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELIFLIG-INMNANKLFCSIIAGLLHYFFLAAFAWMCIE 88
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 468 SFDIWKTFGSTKLKsceKSDLRRQFIwysCYGWGLPTLLTGITIAFTKSDILPDAVrpnfghgrCWF-TYDSFgsasLLF 546
Cdd:cd15437   89 GIHLYLIVVGVIYN---KGFLHKNFY---IFGYGSPAVVVGISAALGYKYYGTTKV--------CWLsTENNF----IWS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 547 FSGPVGILFIINLVLFVLTmkycnkvkneIYKMQSLNSDKPVLKRRFFQDKTRFVMNTKLCFVMGITWLLEIVSILFYDH 626
Cdd:cd15437  151 FIGPACLIILVNLLAFGVI----------IYKVFRHTAMLKPEVSCYENIRSCARGALALLFLLGATWIFGVLHVVYGSV 220
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 281364746 627 KKTFFWTISDSFNvllGIFVFIIF-VFKRRIYNEIMFKF 664
Cdd:cd15437  221 VTAYLFTISNAFQ---GMFIFIFLcVLSRKIQEEYYRLF 256
7tmB2_GPR123 cd16000
G protein-coupled receptor 123, member of the class B2 family of seven-transmembrane G ...
445-654 6.05e-04

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: 42.25  E-value: 6.05e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 445 ICFLSGFFVYFCLMAAFSWMNITSFDIWKTFgSTKLKSCEKSDL----RRQFIWYSCYGWGLPTLLTGITIAFTKSdilp 520
Cdd:cd16000   69 ICQAVGIVLHYSTLSTMLWIGVTARNIYKQV-TKKPHLCQDTDQppypKQPLLRFYLVSGGVPFIICGITAATNIN---- 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 521 davrpNFGHGR-----CWFTYDsfgsASLLFFSGPVGILFIINLVLFVLTMKYCNKVKNEIYKMQSLNSDKPVLKRRFFQ 595
Cdd:cd16000  144 -----NYGTEDedtpyCWMAWE----PSLGAFYGPVAFIVLVTCIYFLCTYVQLRRHPERKYELKNEHSFKAQLRAAAFT 214
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 281364746 596 dktrfvmntklCFVMGITWLLEIVSILFYDHKKTFFWTISDSFNVLLGIFVFIIFVFKR 654
Cdd:cd16000  215 -----------LFLFTATWAFGALAVSQGHFLDMIFSCLYGAFCVTLGLFILIHHCAKR 262
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
365-515 1.76e-03

class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 6 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320160  Cd Length: 321  Bit Score: 40.99  E-value: 1.76e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 365 LYTFLCFdnkVVTGDRIRFKMYPIgLLISCCFYALTLIVYISIaklrnLPGKILIC-LVSSLFAAYLGIALGqlrptSND 443
Cdd:cd15032   27 LFTFLTF---LIDVKRFRYPERPI-IYYSVCYSIVSLMYFIGF-----LLGNSTACnKADEKLELGDTVVLG-----SQN 92
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 281364746 444 DICFLSGFFVYFCLMAAFSW---MNITSFdiwktFGSTKLKSCEKsdLRRQFIWYSCYGWGLPTLLTGITIAFTK 515
Cdd:cd15032   93 KACTVLFMLLYFFTMAGTIWwviLTITWF-----LAAGRKWSCEA--IEQKALWFHAVAWGIPGFLTIMLLAMNK 160
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
385-563 1.83e-03

secretin receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Secretin receptor is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include vasoactive intestinal peptide (VIP), growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors, and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. Secretin, a polypeptide secreted by entero-endocrine S cells in the small intestine, is involved in maintaining body fluid balance. This polypeptide regulates the secretion of bile and bicarbonate into the duodenum from the pancreatic and biliary ducts, as well as regulates the duodenal pH by the control of gastric acid secretion. Studies with secretin receptor-null mice indicate that secretin plays a role in regulating renal water reabsorption. Secretin mediates its biological actions by elevating intracellular cAMP via G protein-coupled secretin receptor, which is expressed in the brain, pancreas, stomach, kidney, and liver.


Pssm-ID: 320403 [Multi-domain]  Cd Length: 271  Bit Score: 40.88  E-value: 1.83e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 385 MYPIGLLISCCFYALTLIVYISIAKLRNLPGKILICLVSSLFAAYLGIALGQLRPTSNDDI---------CFLSGFFVYF 455
Cdd:cd15275    7 MYTVGYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFIKDAVLFSSEDDnhcdiytvgCKVAMVFSNY 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 456 CLMAAFSWMNITSFDIWKtfgstkLKSCEKSDLRRQFIWYSCYGWGLPTLltgITIAFTKSDILPDavrpNFGhgrCWFT 535
Cdd:cd15275   87 CIMANYSWLLVEGLYLHS------LLSISFFSERKHLWWYIALGWGSPLI---FIISWAIARYLHE----NEG---CWDT 150
                        170       180
                 ....*....|....*....|....*...
gi 281364746 536 YDSfgSASLLFFSGPVGILFIINLVLFV 563
Cdd:cd15275  151 RRN--AWIWWIIRGPVILSIFVNFILFL 176
Methuselah_N pfam06652
Methuselah N-terminus; This family represents the N-terminal region of the Drosophila specific ...
247-355 5.78e-03

Methuselah N-terminus; This family represents the N-terminal region of the Drosophila specific Methuselah protein. Drosophila Methuselah (Mth) mutants have a 35% increase in average lifespan and increased resistance to several forms of stress, including heat, starvation, and oxidative damage. The protein affected by this mutation is related to G protein-coupled receptors of the secretin receptor family. Mth, like secretin receptor family members, has a large N-terminal ectodomain, which may constitute the ligand binding site. This family is found in conjunction with pfam00002.


Pssm-ID: 429053  Cd Length: 179  Bit Score: 38.39  E-value: 5.78e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746  247 VRACqemkICQKIPCIRRCCAEGEMYAKGNFStyCKIDGTD--FKFEGFQNLNINANFSKP----SDFgIVH---GLQCP 317
Cdd:pfam06652  52 LRGC----VCKLKPCIRFCCPHGQIYDNGERE--CSDDHEEelTWPDPHLNVTLENGSVVEvhilTDF-VVQrelPLPCD 124
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 281364746  318 -KFRLDPDNfpDDSHTINPSNGSLIIHNTFKTYTNTQYC 355
Cdd:pfam06652 125 eMFSLDKED--NYWQWTLFENGSLLRHFDRVHLSKQEYC 161
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
441-652 6.05e-03

The subfamily B1 of hormone receptors (secretin-like), member of the class B family seven-transmembrane G protein-coupled receptors; The B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, 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 this subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. Moreover, the B1 subfamily receptors play key roles in hormone homeostasis and are promising drug targets in various human diseases including diabetes, osteoporosis, obesity, neurodegenerative conditions (Alzheimer###s and Parkinson's), cardiovascular disease, migraine, and psychiatric disorders (anxiety, depression). Furthermore, the subfamilies B2 and B3 consist of receptors that are capable of interacting with epidermal growth factors (EGF) and the Drosophila melanogaster Methuselah gene product (Mth), respectively. 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: 341321 [Multi-domain]  Cd Length: 273  Bit Score: 39.13  E-value: 6.05e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 441 SNDDICFLSGFFVYFCLMAAFSWMNITSFDIWKTFGSTKLKSceksdlRRQFIWYSCYGWGLPTLLTGI--TIAFTKSDi 518
Cdd:cd15041   77 QNPVGCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSE------PSSLKLYYAIGWGLPLVIVVIwaIVRALLSN- 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 519 lpdavrpnfghGRCWfTYDSFGSaSLLFFSGPVGILFIINLVLFvltmkyCNKVKNEIYKMQSLNSDKPVLKRRFFqdKT 598
Cdd:cd15041  150 -----------ESCW-ISYNNGH-YEWILYGPNLLALLVNLFFL------INILRILLTKLRSHPNAEPSNYRKAV--KA 208
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 281364746 599 RFVmntkLCFVMGITWLLEIvsILFYDHKKtfFWTISDSFNVLL----GIFVFIIFVF 652
Cdd:cd15041  209 TLI----LIPLFGIQYLLTI--YRPPDGSE--GELVYEYFNAILnssqGFFVAVIYCF 258
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
446-563 6.67e-03

growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor (GHRHR) is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal peptide. These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. GHRHR is a specific receptor for the growth hormone-releasing hormone (GHRH) that controls the synthesis and release of growth hormone (GH) from the anterior pituitary somatotrophs. Mutations in the gene encoding GHRHR have been connected to isolated growth hormone deficiency (IGHD), a short-stature condition caused by deficient production of GH or lack of GH action. GHRH is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. GHRHR is found in mammals as well as zebrafish and chicken, whereas the GHRHR type 2, an ortholog of the GHRHR, has only been identified in ray-finned fish, chicken and Xenopus. Xenopus laevis GHRHR2 has been shown to interact with both endogenous GHRH and PACAP-related peptide (PRP).


Pssm-ID: 320398 [Multi-domain]  Cd Length: 268  Bit Score: 39.01  E-value: 6.67e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 446 CFLSGFFVYFCLMAAFSWMNITSFDIWKTFGSTKLKSceksdlRRQFIWYSCYGWGLPTLLTGITIaftksdilpdAVRP 525
Cdd:cd15270   77 CKVSVVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRG------KRYFWWLVLLGWGLPTLCTGTWI----------LCKL 140
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 281364746 526 NFGHGRCWFTYDSfgSASLLFFSGPVGILFIINLVLFV 563
Cdd:cd15270  141 YFEDTECWDINND--SPYWWIIKGPIVISVGVNFLLFL 176
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
414-575 7.24e-03

class F smoothened family membrane region, a homolog of frizzled receptors; This group represents smoothened (SMO), a transmembrane G protein-coupled receptor that acts as the transducer of the hedgehog (HH) signaling pathway. SMO is activated by the hedgehog (HH) family of proteins acting on the 12-transmembrane domain receptor patched (PTCH), which constitutively inhibits SMO. Thus, in the absence of HH proteins, PTCH inhibits SMO signaling. On the other hand, binding of HH to the PTCH receptor activates its internalization and degradation, thereby releasing the PTCH inhibition of SMO. This allows SMO to trigger intracellular signaling and the subsequent activation of the Gli family of zinc finger transcriptional factors and induction of HH target gene expression (PTCH, Gli1, cyclin, Bcl-2, etc). SMO is closely related to the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate family of G-protein coupled receptors. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The WNT and HH signaling pathways play critical roles in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320158  Cd Length: 331  Bit Score: 39.20  E-value: 7.24e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 414 PGKILICLVSSLFAAYLGIaLGQLRPTSNDDI--------------------CFLSGFFVYFCLMAAFSWMNITSFdIWK 473
Cdd:cd15030   44 PAVILFYINACFFIGSIGW-LAQFLPGAREDIvcrkdgtmrlgepsagenlsCVVIFVLVYYFLMAGCVWFVILTY-AWH 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364746 474 TFGSTKLKSCEKSDLRRQFiwYSCYGWGLPTLLTGITIAFTKSDilPDAVrpnfgHGRCWFTYDSFGSASlLFFSGPVGI 553
Cdd:cd15030  122 MSFKALGTIQDRLDKKTAY--FHLIAWSLPLVLTITIMALGQVD--GDSV-----SGICFVGYKNHMYRA-GFVLAPVGL 191
                        170       180
                 ....*....|....*....|..
gi 281364746 554 LFIINLVLFVLTMKYCNKVKNE 575
Cdd:cd15030  192 VLVIGGYFLVRGLYTLIKLKIS 213
 
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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