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Conserved domains on  [gi|134949047|ref|NP_001028665|]
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adhesion G-protein coupled receptor F2 precursor [Mus musculus]

Protein Classification

adhesion G protein-coupled receptor( domain architecture ID 706538)

adhesion G protein-coupled receptor (GPCR) contains a GPCR proteolytic site (GPS) in its N-terminus

Gene Ontology:  GO:0004930|GO:0005886|GO:0007166
SCOP:  2000339

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tm_GPCRs super family cl28897
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
378-624 5.64e-143

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


The actual alignment was detected with superfamily member cd15994:

Pssm-ID: 475119 [Multi-domain]  Cd Length: 267  Bit Score: 416.55  E-value: 5.64e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMADAWFIVASFLSGPVLHHNGCVAAT 457
Cdd:cd15994    1 NAVLDYITRIGLGLSIFSLALCLTIEAVVWSHVTKTEITYMRHVCIVNIATSLLIADVWFILASIVHNTALNYPLCVAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEPGKGYLRPEACWLNWDMTK 537
Cdd:cd15994   81 FFLHFFYLSLFFWMLTKALLILYGILLVFFKITKSVFIATAFSIGYGCPLVIAVLTVAITEPKKGYLRPEACWLNWDETK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 538 ALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATVINGHSLAFHIIF 617
Cdd:cd15994  161 ALLAFIIPALSIVVVNLIVVGVVVVKTQRSSIGESCKQDVSNIIRISKNVAILTPLLGLTWGFGLATIIDSRSLPFHIIF 240

                 ....*..
gi 134949047 618 SLLNALQ 624
Cdd:cd15994  241 ALLNAFQ 247
GPS super family cl02559
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
326-373 7.55e-07

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


The actual alignment was detected with superfamily member smart00303:

Pssm-ID: 470616  Cd Length: 49  Bit Score: 46.23  E-value: 7.55e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 134949047   326 KSQCVGWHSLESRWDWRACKTIQENSRQAVCRCrpNKLyTSFSILMSP 373
Cdd:smart00303   2 NPICVFWDESSGEWSTRGCELLETNGTHTTCSC--NHL-TTFAVLMDV 46
 
Name Accession Description Interval E-value
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
378-624 5.64e-143

orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR111 and GPR115 are highly homologous orphan receptors that belong to group VI adhesion-GPCRs along with GPR110, GPR113, and GPR116. 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. Both GPR111 and GPR5 are present only in land-living animals and are predominantly expressed in the developing skin.


Pssm-ID: 320660 [Multi-domain]  Cd Length: 267  Bit Score: 416.55  E-value: 5.64e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMADAWFIVASFLSGPVLHHNGCVAAT 457
Cdd:cd15994    1 NAVLDYITRIGLGLSIFSLALCLTIEAVVWSHVTKTEITYMRHVCIVNIATSLLIADVWFILASIVHNTALNYPLCVAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEPGKGYLRPEACWLNWDMTK 537
Cdd:cd15994   81 FFLHFFYLSLFFWMLTKALLILYGILLVFFKITKSVFIATAFSIGYGCPLVIAVLTVAITEPKKGYLRPEACWLNWDETK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 538 ALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATVINGHSLAFHIIF 617
Cdd:cd15994  161 ALLAFIIPALSIVVVNLIVVGVVVVKTQRSSIGESCKQDVSNIIRISKNVAILTPLLGLTWGFGLATIIDSRSLPFHIIF 240

                 ....*..
gi 134949047 618 SLLNALQ 624
Cdd:cd15994  241 ALLNAFQ 247
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
380-624 2.77e-27

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: 110.83  E-value: 2.77e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047  380 VLTYITYIGLGISICSLIICLAIEVLVWS-QVTKTEIsyLRHLCIANI-AATLLMADawfIVASFLSGPVLHHN--GCVA 455
Cdd:pfam00002   3 SLKVIYTVGYSLSLVALLLAIAIFLLFRKlHCTRNYI--HLNLFASFIlRALLFLVG---DAVLFNKQDLDHCSwvGCKV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047  456 ATFFVHFFYLSVFFWMLAKAlLILYgILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDm 535
Cdd:pfam00002  78 VAVFLHYFFLANFFWMLVEG-LYLY-TLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVDP--KGYGEDDGCWLSNE- 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047  536 TKALLAFVVPALAIVVVNLITVTMVIIK-TQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATVI--NGHSLA 612
Cdd:pfam00002 153 NGLWWIIRGPILLIILVNFIIFINIVRIlVQKLRETNMGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFAFNpeNTLRVV 232
                         250
                  ....*....|..
gi 134949047  613 FHIIFSLLNALQ 624
Cdd:pfam00002 233 FLYLFLILNSFQ 244
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
326-373 7.55e-07

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


Pssm-ID: 197639  Cd Length: 49  Bit Score: 46.23  E-value: 7.55e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 134949047   326 KSQCVGWHSLESRWDWRACKTIQENSRQAVCRCrpNKLyTSFSILMSP 373
Cdd:smart00303   2 NPICVFWDESSGEWSTRGCELLETNGTHTTCSC--NHL-TTFAVLMDV 46
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
328-370 1.09e-06

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


Pssm-ID: 460350  Cd Length: 44  Bit Score: 45.76  E-value: 1.09e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 134949047  328 QCVGW---HSLESRWDWRACKTIQENSRQAVCRCrpNKLyTSFSIL 370
Cdd:pfam01825   2 QCVFWdftNSTTGRWSTEGCTTVSLNDTHTVCSC--NHL-TSFAVL 44
 
Name Accession Description Interval E-value
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
378-624 5.64e-143

orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR111 and GPR115 are highly homologous orphan receptors that belong to group VI adhesion-GPCRs along with GPR110, GPR113, and GPR116. 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. Both GPR111 and GPR5 are present only in land-living animals and are predominantly expressed in the developing skin.


Pssm-ID: 320660 [Multi-domain]  Cd Length: 267  Bit Score: 416.55  E-value: 5.64e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMADAWFIVASFLSGPVLHHNGCVAAT 457
Cdd:cd15994    1 NAVLDYITRIGLGLSIFSLALCLTIEAVVWSHVTKTEITYMRHVCIVNIATSLLIADVWFILASIVHNTALNYPLCVAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEPGKGYLRPEACWLNWDMTK 537
Cdd:cd15994   81 FFLHFFYLSLFFWMLTKALLILYGILLVFFKITKSVFIATAFSIGYGCPLVIAVLTVAITEPKKGYLRPEACWLNWDETK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 538 ALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATVINGHSLAFHIIF 617
Cdd:cd15994  161 ALLAFIIPALSIVVVNLIVVGVVVVKTQRSSIGESCKQDVSNIIRISKNVAILTPLLGLTWGFGLATIIDSRSLPFHIIF 240

                 ....*..
gi 134949047 618 SLLNALQ 624
Cdd:cd15994  241 ALLNAFQ 247
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
378-624 3.65e-134

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: 393.99  E-value: 3.65e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMADAWFIVASFLSGPVLHHNGCVAAT 457
Cdd:cd15932    1 SPALDYITYVGLGISILSLVLCLIIEALVWKSVTKNKTSYMRHVCLVNIALSLLIADIWFIIGAAISTPPNPSPACTAAT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEPGKGYLRPEACWLNWDMTK 537
Cdd:cd15932   81 FFIHFFYLALFFWMLTLGLLLFYRLVLVFHDMSKSTMMAIAFSLGYGCPLIIAIITVAATAPQGGYTRKGVCWLNWDKTK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 538 ALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMF-QEVRAIVRICKNIAILTPLLGLTWGFGIATVINGHSLAFHII 616
Cdd:cd15932  161 ALLAFVIPALAIVVVNFIILIVVIFKLLRPSVGERPSkDEKNALVQIGKSVAILTPLLGLTWGFGLGTMIDPKSLAFHII 240

                 ....*...
gi 134949047 617 FSLLNALQ 624
Cdd:cd15932  241 FAILNSFQ 248
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
381-624 5.92e-97

The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR116 (also known as Ig-hepta) is an orphan receptor that belongs to group VI adhesion-GPCRs along with GPR110, GPR111, GPR113, and GPR115. 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. GPR116 has four I-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. GPR116 is highly expressed in fetal and adult lung, and it has been shown to regulate lung surfactant levels as well as to stimulate breast cancer metastasis through a G(q)-p63-RhoGEF-Rho GTPase signaling pathway. 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: 320382 [Multi-domain]  Cd Length: 275  Bit Score: 298.64  E-value: 5.92e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMADAWFIVASFL--SGPVLHHNGCVAATF 458
Cdd:cd15254    4 LDYITYIGLSISILSLAICIVIESLVWKSVTKNRTSYMRHVCILNIAVSLLIADIWFIVVAAIqdQNYAVNGNVCVAATF 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 FVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEPGKGYLRPEACWLNWDMTKA 538
Cdd:cd15254   84 FIHFFYLCVFFWMLALGLMLFYRLVFILHDTSKTIQKAVAFCLGYGCPLIISVITIAVTLPRDSYTRKKVCWLNWEDSKA 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 539 LLAFVVPALAIVVVNLITVTMVIIKTQRAAIGS-SMFQEVRAIVRICKNIAILTPLLGLTWGFGIATVINGHSLAFHIIF 617
Cdd:cd15254  164 LLAFVIPALIIVAVNSIITVVVIVKILRPSIGEkPSKQERSSLFQIIKSIGVLTPLLGLTWGFGLATVIKGSSIVFHILF 243

                 ....*..
gi 134949047 618 SLLNALQ 624
Cdd:cd15254  244 TLLNAFQ 250
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
378-624 3.11e-72

orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G protein-coupled receptors; GPR113 is an orphan receptor that belongs to group VI adhesion-GPCRs along with GPR110, GPR111, GPR115, and GPR116. 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. GPR113 contains a hormone binding domain and one EGF (epidermal grown factor) domain, and is primarily expressed in a subset of taste receptor cells. 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: 320381 [Multi-domain]  Cd Length: 271  Bit Score: 234.27  E-value: 3.11e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMADAWFIVASFLSgpVLHHNG-CVAA 456
Cdd:cd15253    1 SFWLDFLSQVGLGASILALLLCLGIYRLVWRSVVRNKISYFRHMTLVNIAFSLLLADTCFLGATFLS--AGHESPlCLAA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 457 TFFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEPGKGYLRPEACWLNWDmT 536
Cdd:cd15253   79 AFLCHFFYLATFFWMLVQALMLFHQLLFVFHQLAKRSVLPLMVTLGYLCPLLIAAATVAYYYPKRQYLHEGACWLNGE-S 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 537 KALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVR-AIVRICKNIAILTPLLGLTWGFGIATVINGHSLAFHI 615
Cdd:cd15253  158 GAIYAFSIPVLAIVLVNLLVLFVVLMKLMRPSVSEGPPPEERkALLSIFKALLVLTPVFGLTWGLGVATLTGESSQVSHY 237

                 ....*....
gi 134949047 616 IFSLLNALQ 624
Cdd:cd15253  238 GFAILNAFQ 246
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
380-624 4.11e-45

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: 161.20  E-value: 4.11e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLmadawFIVASFLSGpvlHHNGCVAATFF 459
Cdd:cd15040    3 ALSIITYIGCGLSLLGLLLTIITYILFRKLRKRKPTKILLNLCLALLLANLL-----FLFGINSTD---NPVLCTAVAAL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 460 VHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASlFSVGYGCPLVIAIITLAVTEPGkGYLRPEACWLNWDMTkAL 539
Cdd:cd15040   75 LHYFLLASFMWMLVEALLLYLRLVKVFGTYPRHFILKY-ALIGWGLPLIIVIITLAVDPDS-YGNSSGYCWLSNGNG-LY 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 540 LAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAIVRIcKNIAILTPLLGLTWGFGIATVINGHsLAFHIIFSL 619
Cdd:cd15040  152 YAFLGPVLLIILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQL-RAAVSLFFLLGLTWIFGILAIFGAR-VVFQYLFAI 229

                 ....*
gi 134949047 620 LNALQ 624
Cdd:cd15040  230 FNSLQ 234
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
378-624 1.20e-40

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: 148.90  E-value: 1.20e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISICSLIICLAIEVLVWSqvtkteISYLRHLCIANIAATLLMADAWFIVASFLSGPvLHHNGCVAAT 457
Cdd:cd13952    1 DLALSIITYIGCSLSLVGLLLTIITYLLFPK------LRNLRGKILINLCLSLLLAQLLFLIGQLLTSS-DRPVLCKALA 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASLFsVGYGCPLVIAIITLAV---TEPGKGYLRPEACWLNWD 534
Cdd:cd13952   74 ILLHYFLLASFFWMLVEAFDLYRTFVKVFGSSERRRFLKYSL-YGWGLPLLIVIITAIVdfsLYGPSPGYGGEYCWLSNG 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 535 MTkALLAFVVPALAIVVVNLITVTMV---IIKTQRAAIGSSMFQEVRAIVRICkniAILTPLLGLTWGFGIATVINGHSL 611
Cdd:cd13952  153 NA-LLWAFYGPVLLILLVNLVFFILTvriLLRKLRETPKQSERKSDRKQLRAY---LKLFPLMGLTWIFGILAPFVGGSL 228
                        250
                 ....*....|...
gi 134949047 612 AFHIIFSLLNALQ 624
Cdd:cd13952  229 VFWYLFDILNSLQ 241
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
380-625 1.70e-38

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: 142.85  E-value: 1.70e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLAIEVLVwsQVTKTEisylRHLCIANIAATLLMADAwFIVASflSGPVLHHNGCVAATFF 459
Cdd:cd15933    3 ALSIISYIGCGISIACLALTLIIFLVL--RVLSSD----RFQIHKNLCVALLLAQI-LLLAG--EWAEGNKVACKVVAIL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 460 VHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLvasLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmTKAL 539
Cdd:cd15933   74 LHFFFMAAFSWMLVEGLHLYLMIVKVFNYKSKMRY---YYFIGWGLPAIIVAISLAILF--DDYGSPNVCWLSLD-DGLI 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 540 LAFVVPALAIVVVN---LITVTMVIIK--TQRAAIGSSMFQEVRAIVricKNIAILTPLLGLTWGFGIaTVINGHSLAFH 614
Cdd:cd15933  148 WAFVGPVIFIITVNtviLILVVKITVSlsTNDAKKSQGTLAQIKSTA---KASVVLLPILGLTWLFGV-LVVNSQTIVFQ 223
                        250
                 ....*....|.
gi 134949047 615 IIFSLLNALQV 625
Cdd:cd15933  224 YIFVILNSLQG 234
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
380-624 2.77e-27

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: 110.83  E-value: 2.77e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047  380 VLTYITYIGLGISICSLIICLAIEVLVWS-QVTKTEIsyLRHLCIANI-AATLLMADawfIVASFLSGPVLHHN--GCVA 455
Cdd:pfam00002   3 SLKVIYTVGYSLSLVALLLAIAIFLLFRKlHCTRNYI--HLNLFASFIlRALLFLVG---DAVLFNKQDLDHCSwvGCKV 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047  456 ATFFVHFFYLSVFFWMLAKAlLILYgILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDm 535
Cdd:pfam00002  78 VAVFLHYFFLANFFWMLVEG-LYLY-TLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVDP--KGYGEDDGCWLSNE- 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047  536 TKALLAFVVPALAIVVVNLITVTMVIIK-TQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATVI--NGHSLA 612
Cdd:pfam00002 153 NGLWWIIRGPILLIILVNFIIFINIVRIlVQKLRETNMGKSDLKQYRRLAKSTLLLLPLLGITWVFGLFAFNpeNTLRVV 232
                         250
                  ....*....|..
gi 134949047  613 FHIIFSLLNALQ 624
Cdd:pfam00002 233 FLYLFLILNSFQ 244
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
381-624 5.60e-26

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


Pssm-ID: 320384 [Multi-domain]  Cd Length: 260  Bit Score: 107.32  E-value: 5.60e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHlciANIAATLLMADAWFIVASFLSGPVLhhnGCVAATFFV 460
Cdd:cd15256    4 LSSITYVGCSLSIFCLAITLVTFAVLSSVSTIRNQRYHIH---ANLSFAVLVAQILLLISFRFEPGTL---PCKIMAILL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 461 HFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVasLFSVGYGCPLVIAIITLavTEPGKGYLRPEACWLNWDmTKALL 540
Cdd:cd15256   78 HFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFY--YYGIGWGSPLLICIISL--TSALDSYGESDNCWLSLE-NGAIW 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 541 AFVVPALAIVVVN---LITVTMVIikTQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATViNGHSLAFHIIF 617
Cdd:cd15256  153 AFVAPALFVIVVNigiLIAVTRVI--SRISADNYKVHGDANAFKLTAKAVAVLLPILGSSWVFGVLAV-NTHALVFQYMF 229

                 ....*..
gi 134949047 618 SLLNALQ 624
Cdd:cd15256  230 AIFNSLQ 236
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
380-624 5.28e-25

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: 104.65  E-value: 5.28e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLAIEVLVwSQVTKTEISYLRHLCianiaATLLMADAWFIVA-SFLSGPVLhhngCVAATF 458
Cdd:cd15440    3 ALTFITYIGCIISIVCLLLAFITFTCF-RNLQCDRNTIHKNLC-----LCLLIAEIVFLLGiDQTENRTL----CGVIAG 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 FVHFFYLSVFFWMLAKALLILYGILIVFHtlPKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmTKA 538
Cdd:cd15440   73 LLHYFFLAAFSWMLLEGFQLYVMLVEVFE--PEKSRIKWYYLFGYGLPALIVAVSAGVDP--TGYGTEDHCWLSTE-NGF 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 539 LLAFVVPALAIVVVNLITVTMVI---IKTQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATvINGHSLAFHI 615
Cdd:cd15440  148 IWSFVGPVIVVLLANLVFLGMAIyvmCRHSSRSASKKDASKLKNIRGWLKGSIVLVVLLGLTWTFGLLF-INQESIVMAY 226

                 ....*....
gi 134949047 616 IFSLLNALQ 624
Cdd:cd15440  227 IFTILNSLQ 235
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
378-624 1.23e-23

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: 100.76  E-value: 1.23e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISICSLIICLAIEVLvwsqvtkteISYLRHL---CIANIAATLLMADAWFIVASFLSGPvlHHNGCV 454
Cdd:cd15039    1 SSILGILTLIGLIISLVFLLLTLAVYAL---------LPELRNLhgkCLMCLVLSLFVAYLLLLIGQLLSSG--DSTLCV 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 455 AATFFVHFFYLSVFFWMLAKALLILY-----GILIVFHTLPKSCLVASLFsvGYGCPLVIAIITLAVTE-PGKGYLRP-- 526
Cdd:cd15039   70 ALGILLHFFFLAAFFWLNVMSFDIWRtfrgkRSSSSRSKERKRFLRYSLY--AWGVPLLLVAVTIIVDFsPNTDSLRPgy 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 527 --EACWLNwDMTKALLAFVVPALAIVVVNLITVTMV---IIKTQR-AAIGSSMFQEVRAIVRICKNIAILTpllGLTWGF 600
Cdd:cd15039  148 geGSCWIS-NPWALLLYFYGPVALLLLFNIILFILTairIRKVKKeTAKVQSRLRSDKQRFRLYLKLFVIM---GVTWIL 223
                        250       260
                 ....*....|....*....|....
gi 134949047 601 GIATVINGHSLAFHIIFSLLNALQ 624
Cdd:cd15039  224 EIISWFVGGSSVLWYIFDILNGLQ 247
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
384-624 4.83e-21

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: 93.08  E-value: 4.83e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 384 ITYIGLGISICSLIICLAIEVLVWSQVTKTEISYlrhlciANIAATLLMADAWFIVASFLSGPVLHhngCVAATFFVHFF 463
Cdd:cd15441    7 VTYIGIGISLVLLVIAFLVLSCLRGLQSNSNSIH------KNLVACLLLAELLFLLGINQTENLFP---CKLIAILLHYF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 464 YLSVFFWMLAKALLiLYGILIVFHTLPKsCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLnwdMTKALL--A 541
Cdd:cd15441   78 YLSAFSWLLVESLH-LYRMLTEPRDINH-GHMRFYYLLGYGIPAIIVGLSVGLRP--DGYGNPDFCWL---SVNETLiwS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 542 FVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAIVRICkniAILTPLLGLTWGFGIATViNGHSLAFHIIFSLLN 621
Cdd:cd15441  151 FAGPIAFVIVITLIIFILALRASCTLKRHVLEKASVRTDLRSS---FLLLPLLGATWVFGLLAV-NEDSELLHYLFAGLN 226

                 ...
gi 134949047 622 ALQ 624
Cdd:cd15441  227 FLQ 229
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
378-624 1.62e-19

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: 88.55  E-value: 1.62e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISICSLIICLAIEVLVWSqVTKTEISYLRHLCIAniaatLLMADAWFIVASFLSGPVLhhnGCVAAT 457
Cdd:cd15439    1 DLALTVITYVGLIISLLCLFLAILTFLLCRS-IRNTSTSLHLQLSLC-----LFLADLLFLVGIDRTDNKV---LCSIIA 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKAL---LILYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNwd 534
Cdd:cd15439   72 GFLHYLFLACFAWMFLEAVhlfLTVRNLKVVNYFSSHRFKKRFMYPVGYGLPAVIVAISAAVNP--QGYGTPKHCWLS-- 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 535 MTKALL-AFVVPALAIVVVNLI--TVTMVIIKTQRAAIGS--SMFQEVRAIvrICKNIAILTpLLGLTWGFGIATVINGH 609
Cdd:cd15439  148 MEKGFIwSFLGPVCVIIVINLVlfCLTLWILREKLSSLNAevSTLKNTRLL--TFKAIAQLF-ILGCTWILGLFQVGPVA 224
                        250
                 ....*....|....*
gi 134949047 610 SLAFHiIFSLLNALQ 624
Cdd:cd15439  225 TVMAY-LFTITNSLQ 238
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
381-624 6.68e-19

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: 86.74  E-value: 6.68e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLIICLAIEVLVWS-QVTKTEISYlrHLCIANIAATLLmadawfivasFLSGPVLHHN--GCVAAT 457
Cdd:cd15438    4 LTLITKVGLSVSLFCLFLCILTFLFCRSiRGTRNTIHL--HLCLSLFLAHLI----------FLLGINNTNNqvACAVVA 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKALLILYGILIVFHTlpKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmTK 537
Cdd:cd15438   72 GLLHYFFLAAFCWMSLEGVELYLMVVQVFNT--QSLKKRYLLLIGYGVPLVIVAISAAVNS--KGYGTQRHCWLSLE-RG 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 538 ALLAFVVPALAIVVVNLITVTMVIIK-TQR-AAIGSSMFQEVRAIVRICKNIAILTpLLGLTWGFGIaTVINGHSLAFHI 615
Cdd:cd15438  147 FLWSFLGPVCLIILVNAIIFVITVWKlAEKfSSINPDMEKLRKIRALTITAIAQLC-ILGCTWIFGF-FQFSDSTLVMSY 224

                 ....*....
gi 134949047 616 IFSLLNALQ 624
Cdd:cd15438  225 LFTILNSLQ 233
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
380-624 1.36e-18

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: 86.02  E-value: 1.36e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLaIEVLVWSQVTKTEISYLRHLCIANIAATLLmadawfivasFLSGPVLHHNGCVAATF- 458
Cdd:cd15252    3 ILTRITQVGIIISLVCLAICI-FTFWFFRGLQSDRTTIHKNLCISLFLAELV----------FLIGINTTTNKIFCSVIa 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 -FVHFFYLSVFFWMLAKALLILYGILIVFHTlpKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmTK 537
Cdd:cd15252   72 gLLHYFFLAAFAWMFIEGIQLYLMLVEVFEN--EGSRHKNFYIFGYGSPAVIVGVSAALGY--RYYGTTKVCWLSTE-NY 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 538 ALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAIVRICKNIAI-LTPLLGLTWGFGIaTVINGHSLAFHII 616
Cdd:cd15252  147 FIWSFIGPATLIILLNLIFLGVAIYKMFRHTAGLKPEVSCLENIRSWARGAIaLLFLLGLTWIFGV-LHINHASVVMAYL 225

                 ....*...
gi 134949047 617 FSLLNALQ 624
Cdd:cd15252  226 FTVSNSLQ 233
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
380-624 7.71e-18

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: 83.94  E-value: 7.71e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISIcsliICLAIEVLVWSQVTKTEISYLRHLCIaNIAATLLMADAWFIVASFLSGpVLHHNGCVAATFF 459
Cdd:cd15997    3 ILTLITYLGCGISS----IFLGITLVTYLAFEKLRRDYPSKILI-NLCTALLMLNLVFLLNSWLSS-FNNYGLCITVAAF 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 460 VHFFYLSVFFWMLAKALLILYGILIVFHT-LPKSCLVASLfsVGYGCPLVIAIITLAV------TEPGKGYLRPEA--CW 530
Cdd:cd15997   77 LHYFLLASFTWMGLEAVHMYFALVKVFNIyIPNYILKFCI--AGWGIPAVVVALVLAInkdfygNELSSDSLHPSTpfCW 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 531 LNWD-------MTKALLAFVVpALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAivricknIAILTPLLGLTWGF--- 600
Cdd:cd15997  155 IQDDvvfyisvVAYFCLIFLC-NISMFITVLIQIRSMKAKKPSRNWKQGFLHDLKS-------VASLTFLLGLTWGFaff 226
                        250       260
                 ....*....|....*....|....*.
gi 134949047 601 --GIATVInghslaFHIIFSLLNALQ 624
Cdd:cd15997  227 awGPVRIF------FLYLFSICNTLQ 246
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
379-624 4.46e-17

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: 81.41  E-value: 4.46e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 379 PVLTYITYIGLGISICSLIICLAIEVLV-WSQVTKTEISYlrHLCIaniaaTLLMADAWFIVASFLSGPVLhhnGCVAAT 457
Cdd:cd15931    2 PFLEWINRVGVIVSLFCLGLAIFTFLLCrWIPKINTTAHL--HLCL-----CLSMSHTLFLAGIEYVENEL---ACTVMA 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKAL---LILYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWD 534
Cdd:cd15931   72 GLLHYLFLASFVWMLLEALqlhLLVRRLTKVQVIQRDGLPRPLLCLIGYGVPFLIVGVSALVYS--DGYGEAKMCWLSQE 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 535 mTKALLAFVVPALAIVVVN--LITVTMVIIKTQRAAIGSSMFQEVRAIVRICKNIAILTpLLGLTWGFGIaTVINGHSLA 612
Cdd:cd15931  150 -RGFNWSFLGPVIAIIGINwiLFCATLWCLRQTLSNMNSDISQLKDTRLLTFKAVAQLF-ILGCTWVLGL-FQTNPVALV 226
                        250
                 ....*....|..
gi 134949047 613 FHIIFSLLNALQ 624
Cdd:cd15931  227 FQYLFTILNSLQ 238
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
381-641 1.06e-16

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: 80.66  E-value: 1.06e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLIICLAIEVLVwsQVTKTEisylRHLCIANIAATLLMADAWFIVASFLSGpvlHHNGCVAATFFV 460
Cdd:cd15255    4 LRTLSFIGCGVSLCALIVTFILFLAV--GVPKSE----RTTVHKNLIFALAAAEFLLMFSEWAKG---NQVACWAVTALL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 461 HFFYLSVFFWMLAKALLILYGILIVfhTLPKSCLVASLFSVGYGCPLVIAIITLAVTePGKgYLRPEACWLNWDmTKALL 540
Cdd:cd15255   75 HLFFLAAFSWMLVEGLLLWSKVVAV--NMSEDRRMKFYYVTGWGLPVVIVAVTLATS-FNK-YVADQHCWLNVQ-TDIIW 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 541 AFVVPALAIVVVN---LITVTMVIIKTQR------AAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATVInghSL 611
Cdd:cd15255  150 AFVGPVLFVLTVNtfvLFRVVMVTVSSARrrakmlTPSSDLEKQIGIQIWATAKPVLVLLPVLGLTWLCGVLVHL---SD 226
                        250       260       270
                 ....*....|....*....|....*....|....
gi 134949047 612 AFHIIFSLLNALQ----VSPDAAVDSELRECVHR 641
Cdd:cd15255  227 VWAYVFITLNSFQglyiFLVYAIYNSEVRNAIQR 260
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
378-624 1.35e-16

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: 79.99  E-value: 1.35e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYItyIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMadawfivasfLSGPVLHHNG--CVA 455
Cdd:cd15251    3 SPSVTLI--VGCGVSCLALLTLLAIYAAFWRYIRSERSIILINFCLSIISSNILI----------LVGQTQTLNKgvCTM 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 456 ATFFVHFFYLSVFFWMLAKAlliLYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEpGKGYLRPEACWLNWDm 535
Cdd:cd15251   71 TAAFLHFFFLSSFCWVLTEA---WQSYMAVTGRMRTRLIRKRFLCLGWGLPALVVAVSVGFTR-TKGYGTSSYCWLSLE- 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 536 TKALLAFVVPALAIVVVNLITVTMVIIK-TQRAAIGSsmfqevRAIVRICKNIAILtPLLGLTWGFGIATVINGHSLAFH 614
Cdd:cd15251  146 GGLLYAFVGPAAAVVLVNMVIGILVFNKlVSRDGISD------NAMASLWSSCVVL-PLLALTWMSAVLAMTDRRSVLFQ 218
                        250
                 ....*....|
gi 134949047 615 IIFSLLNALQ 624
Cdd:cd15251  219 ILFAVFDSLQ 228
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
380-624 7.63e-15

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: 75.14  E-value: 7.63e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISIcsliICLAIEVLVWSQVTKTEISYLRHLCIaNIAATLLMADAWFIVASF--LSGPVlhhNGCVAAT 457
Cdd:cd15258    3 ILTFISYVGCGISA----IFLAITILTYIAFRKLRRDYPSKIHM-NLCAALLLLNLAFLLSSWiaSFGSD---GLCIAVA 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKALLILYGILIVFHT-LPKSCLVASLfsVGYGCPLVIAIITLAVTEPGKGYLR---------PE 527
Cdd:cd15258   75 VALHYFLLACLTWMGLEAFHLYLLLVKVFNTyIRRYILKLCL--VGWGLPALLVTLVLSVRSDNYGPITipngegfqnDS 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 528 ACWLNWD----MTKALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMfqevraIVRICKNIAILTPLLGLTWGFGIA 603
Cdd:cd15258  153 FCWIRDPvvfyITVVGYFGLTFLFNMVMLATVLVQICRLREKAQATPRKR------ALHDLLTLLGLTFLLGLTWGLAFF 226
                        250       260
                 ....*....|....*....|.
gi 134949047 604 TvINGHSLAFHIIFSLLNALQ 624
Cdd:cd15258  227 A-WGPFNLPFLYLFAIFNSLQ 246
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
380-624 9.88e-15

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: 74.86  E-value: 9.88e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISIcsliICLAIEVLVWSQVTKTEISY----LRHLCIANIAATL-LMADAWFIVASFLSGPvlhhngCV 454
Cdd:cd15444    3 ILTFITYIGCGLSA----IFLSVTLVTYIAFEKIRRDYpskiLIQLCVALLLLNLvFLLDSWIALYKDIVGL------CI 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 455 AATFFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVaSLFSVGYGCPLVIAIITLAVTEPGKGYLR--------- 525
Cdd:cd15444   73 SVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYIRKYIL-KFCIVGWGVPAVVVAIVLAVSKDNYGLGSygkspngst 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 526 PEACWLNWDmtkalLAFVVPALA-IVVVNLITVTM---VIIKTQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFG 601
Cdd:cd15444  152 DDFCWINNN-----IVFYITVVGyFCVIFLLNISMfivVLVQLCRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITWGFA 226
                        250       260
                 ....*....|....*....|...
gi 134949047 602 IATVINGhSLAFHIIFSLLNALQ 624
Cdd:cd15444  227 FFAWGPV-NLAFMYLFAIFNTLQ 248
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
380-624 1.38e-14

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: 74.14  E-value: 1.38e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLaIEVLVWSQVTKTEISYLRHLCIAniaatLLMADAWFIVASFLSGPVLHhngCVAATFF 459
Cdd:cd15437    3 VLTRITQLGIIISLICLSMCI-FTFWFFSEIQSTRTTIHKNLCCS-----LFLAELIFLIGINMNANKLF---CSIIAGL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 460 VHFFYLSVFFWMLAKAL---LILYGILivfhtLPKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmT 536
Cdd:cd15437   74 LHYFFLAAFAWMCIEGIhlyLIVVGVI-----YNKGFLHKNFYIFGYGSPAVVVGISAALGY--KYYGTTKVCWLSTE-N 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 537 KALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGS----SMFQEVRAIVRicKNIAILTpLLGLTWGFGIATVINGHSLA 612
Cdd:cd15437  146 NFIWSFIGPACLIILVNLLAFGVIIYKVFRHTAMLkpevSCYENIRSCAR--GALALLF-LLGATWIFGVLHVVYGSVVT 222
                        250
                 ....*....|..
gi 134949047 613 FHiIFSLLNALQ 624
Cdd:cd15437  223 AY-LFTISNAFQ 233
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
378-624 7.72e-14

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: 72.23  E-value: 7.72e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYITYIGLGISIcsliICLAIEVLVWSQVTKTEISYLRHLcIANIAATLLMADAWFIVASFLSGpvLHHNG-CVAA 456
Cdd:cd15996    1 TRVLTFITYIGCGISA----IFSAATLLTYIAFEKLRRDYPSKI-LMNLSTALLFLNLVFLLDGWIAS--FEIDElCITV 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 457 TFFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVaSLFSVGYGCPLVIAIITLAVTEPGKGYLR----------P 526
Cdd:cd15996   74 AVLLHFFLLATFTWMGLEAIHMYIALVKVFNTYIRRYIL-KFCIIGWGLPALIVSIVLASTNDNYGYGYygkdkdgqggD 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 527 EACWLnwdmtKALLAFVVPALA------IVVVNLITVTMVIIKTQRAAIGSSMFQEvrAIVRICKNIAILTPLLGLTWGF 600
Cdd:cd15996  153 EFCWI-----KNPVVFYVTCAAyfgimfLMNVAMFIVVMVQICGRNGKRSNRTLRE--EILRNLRSVVSLTFLLGMTWGF 225
                        250       260
                 ....*....|....*....|....
gi 134949047 601 GIaTVINGHSLAFHIIFSLLNALQ 624
Cdd:cd15996  226 AF-FAWGPVNLAFMYLFTIFNSLQ 248
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
387-624 7.87e-14

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: 72.29  E-value: 7.87e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 387 IGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMADAwfivasflSGPVLHHNGCVAATFFVHFFYLS 466
Cdd:cd15988   10 IGCAVSCMALLILLAIYAAFWRFIRSERSIILLNFCLSILASNILILVG--------QSQTLSKGVCTMTAAFLHFFFLS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 467 VFFWMLAKALlilYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEPgKGYLRPEACWLNWDmTKALLAFVVPA 546
Cdd:cd15988   82 SFCWVLTEAW---QSYLAVIGRMRTRLVRKRFLCLGWGLPALVVAVSVGFTRT-KGYGTASYCWLSLE-GGLLYAFVGPA 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 547 LAIVVVNLITVTMVI------------IKTQRAAIGSSMFQEVRAIVRICKNIA--------------------ILTPLL 594
Cdd:cd15988  157 AVIVLVNMLIGIIVFnklmsrdgisdkSKKQRAGSEAEPCSSLLLKCSKCGVVSsaamssatassamaslwsscVVLPLL 236
                        250       260       270
                 ....*....|....*....|....*....|
gi 134949047 595 GLTWGFGIATVINGHSLAFHIIFSLLNALQ 624
Cdd:cd15988  237 ALTWMSAVLAMTDRRSILFQVLFAVFNSVQ 266
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
379-624 3.53e-13

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: 70.33  E-value: 3.53e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 379 PVLTYITYIGLGISICSLIICLAIeVLVWSQVTKTEISYLRHLCIANI--AATLLMADAWFIVASFLS---GPVLHHN-- 451
Cdd:cd15041    2 LVVYYIYLVGYSLSLVALLPAIVI-FLYFRSLRCTRIRLHINLFLSFIlrAVFWIIWDLLVVYDRLTSsgvETVLMQNpv 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 452 GCVAATFFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSclVASLFSVGYGCPLVIAIITLAVtepgKGYLRPEACWL 531
Cdd:cd15041   81 GCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSS--LKLYYAIGWGLPLVIVVIWAIV----RALLSNESCWI 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 532 NWDMTKALLAFVVPALAIVVVNLITVTMV--IIKTQ-RAAIGSSMFQEVRAIvricKNIAILTPLLGLTWGFGIATVING 608
Cdd:cd15041  155 SYNNGHYEWILYGPNLLALLVNLFFLINIlrILLTKlRSHPNAEPSNYRKAV----KATLILIPLFGIQYLLTIYRPPDG 230
                        250
                 ....*....|....*...
gi 134949047 609 HSL--AFHIIFSLLNALQ 624
Cdd:cd15041  231 SEGelVYEYFNAILNSSQ 248
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
453-624 1.69e-12

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: 68.75  E-value: 1.69e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 453 CVAATFFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASlFSVGYGCPLVIAIITLAVT--EPG------KGYL 524
Cdd:cd15257   93 CTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQA-SAIGWGIPAVVVAITLGATyrFPTslpvftRTYR 171
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 525 RPEACWL-----NWDMTKALL-AFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAIVRICKNIAILTpLLGLTW 598
Cdd:cd15257  172 QEEFCWLaaldkNFDIKKPLLwGFLLPVGLILITNVILFIMTSQKVLKKNNKKLTTKKRSYMKKIYITVSVAV-VFGITW 250
                        170       180
                 ....*....|....*....|....*...
gi 134949047 599 GFGIATVINGHS--LAFHIIFSLLNALQ 624
Cdd:cd15257  251 ILGYLMLVNNDLskLVFSYIFCITNTTQ 278
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
376-624 2.13e-12

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: 67.71  E-value: 2.13e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 376 LESPVLTYITYI-GLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMadawfivasfLSGPVLHHNG-- 452
Cdd:cd15990    1 MEKALLPSVTLIvGCGVSSLTLLLLIIIYVSVWRYIRSERSVILINFCLSIISSNALI----------LIGQTQTRNKvv 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 453 CVAATFFVHFFYLSVFFWMLAKALlilYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEpGKGYLRPEACWLN 532
Cdd:cd15990   71 CTLVAAFLHFFFLSSFCWVLTEAW---QSYMAVTGRLRNRIIRKRFLCLGWGLPALVVAISVGFTK-AKGYGTVNYCWLS 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 533 WDmTKALLAFVVPALAIVVVNLITVTMVIIK-TQRAAIGSSMFQEvRAIVRICKNIAILtPLLGLTWGFGIATVINGHSL 611
Cdd:cd15990  147 LE-GGLLYAFVGPAAAVVLVNMVIGILVFNKlVSKDGITDKKLKE-RAGASLWSSCVVL-PLLALTWMSAVLAITDRRSA 223
                        250
                 ....*....|...
gi 134949047 612 AFHIIFSLLNALQ 624
Cdd:cd15990  224 LFQILFAVFDSLE 236
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
380-624 6.05e-12

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: 66.48  E-value: 6.05e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYlRHLCIANIAATLLmadawfivasFLSGPVLHHNGCVAATF- 458
Cdd:cd16007    3 LLSVITWVGIVISLVCLAICISTFCFLRGLQTDRNTIH-KNLCINLFLAELL----------FLIGIDKTQYQIACPIFa 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 -FVHFFYLSVFFWMLAKALLILYGILIVFHTlpKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmTK 537
Cdd:cd16007   72 gLLHFFFLAAFSWLCLEGVQLYLMLVEVFES--EYSRKKYYYLCGYCFPALVVGISAAIDY--RSYGTEKACWLRVD-NY 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 538 ALLAFVVPALAIVVVNLITVTMVIIKTQRAaigSSMFQEVRAIVRICKNIAI----LTPLLGLTWGFGIaTVINGHSLAF 613
Cdd:cd16007  147 FIWSFIGPVSFVIVVNLVFLMVTLHKMIRS---SSVLKPDSSRLDNIKSWALgaitLLFLLGLTWAFGL-LFINKESVVM 222
                        250
                 ....*....|.
gi 134949047 614 HIIFSLLNALQ 624
Cdd:cd16007  223 AYLFTTFNAFQ 233
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
383-596 1.06e-11

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


Pssm-ID: 320388 [Multi-domain]  Cd Length: 267  Bit Score: 65.76  E-value: 1.06e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 383 YITYIGLGISICSLIICLAIeVLVWSQVTKTEISYLRHLCIAnIAATLLMADAWFIVASFlSGPVLHHNG--CVAATFFV 460
Cdd:cd15260    6 YVYIGGYSVSLIALIISLAI-FFSFRSLRCTRITIHMNLFIS-FALNNLLWIVWYKLVVD-NPEVLLENPiwCQALHVLL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 461 HFFYLSVFFWMLAKALLILYGILIVFhtLPKSCLVASLFSVGYGCPLVIAIITLAVtepgKGYLRPE--ACWLNWDMTKA 538
Cdd:cd15260   83 QYFMVCNYFWMFCEGLYLHTVLVVAF--ISEKSLMRWFIAIGWGVPLVITAIYAGV----RASLPDDteRCWMEESSYQW 156
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 134949047 539 LL-AFVVPALAIVVVNLITVTMVIIKTQRAAIGSSmfqEVRAIVRICKNIAILTPLLGL 596
Cdd:cd15260  157 ILiVPVVLSLLINLIFLINIVRVLLTKLRATSPNP---APAGLRKAVRATLILIPLLGL 212
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
380-624 9.58e-11

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: 62.63  E-value: 9.58e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISIcsliICLAIEVLVWSQVTKTEISylRHLCIANIAATLLMADAWFIVASFLSGPVLhhnGCVAATFF 459
Cdd:cd16006    3 LLTVITWVGIVISL----VCLAICIFTFCFFRGLQSD--RNTIHKNLCINLFIAEFIFLIGIDKTEYKI---ACPIFAGL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 460 VHFFYLSVFFWMLAKALLILYGILIVFHTlpKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmTKAL 539
Cdd:cd16006   74 LHFFFLAAFAWMCLEGVQLYLMLVEVFES--EYSRKKYYYVAGYLFPATVVGVSAAIDY--KSYGTEKACWLRVD-NYFI 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 540 LAFVVPALAIVVVNLITVTMVIIKTQRAAIG----SSMFQEVRAIVricKNIAILTPLLGLTWGFGIaTVINGHSLAFHI 615
Cdd:cd16006  149 WSFIGPVTFIILLNLIFLVITLCKMVKHSNTlkpdSSRLENIKSWV---LGAFALLCLLGLTWSFGL-LFINEETIVMAY 224

                 ....*....
gi 134949047 616 IFSLLNALQ 624
Cdd:cd16006  225 LFTIFNAFQ 233
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
380-624 1.16e-10

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


Pssm-ID: 320671 [Multi-domain]  Cd Length: 258  Bit Score: 62.65  E-value: 1.16e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLaIEVLVWSQVTKTEISYLRHLCIaniaaTLLMADAWFIVA-SFLSGPVlhhnGCVAATF 458
Cdd:cd16005    3 LLDVITWVGILLSLVCLLICI-FTFCFFRGLQSDRNTIHKNLCI-----SLFVAELLFLIGiNRTDQPI----ACAVFAA 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 FVHFFYLSVFFWMLAKALLILYGILIVFHTlpKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmTKA 538
Cdd:cd16005   73 LLHFFFLAAFTWMFLEGVQLYIMLVEVFES--EHSRRKYFYLVGYGMPALIVAVSAAVDY--RSYGTDKVCWLRLD-TYF 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 539 LLAFVVPALAIVVVNLITVTMVIIKT--QRAAIGSSMFQEVRAIVRICKNIAILTpLLGLTWGFGIaTVINGHSLAFHII 616
Cdd:cd16005  148 IWSFIGPATLIIMLNVIFLGIALYKMfhHTAILKPESGCLDNIKSWVIGAIALLC-LLGLTWAFGL-MYINESTVIMAYL 225

                 ....*...
gi 134949047 617 FSLLNALQ 624
Cdd:cd16005  226 FTIFNSLQ 233
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
381-624 1.41e-10

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: 62.17  E-value: 1.41e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLIICLAIEVLVwsqvtKTEISYLrHLCIANIAATLLMADAWFIVA-SFLSGPVLhhngCVAATFF 459
Cdd:cd15991    4 LKIITYTTVSLSLVALLITFILLVLI-----RTLRSNL-HSIHKNLVAALFFSELIFLIGiNQTENPFV----CTVVAIL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 460 VHFFYLSVFFWMLAKALLIlYGILIVFHTLpKSCLVASLFSVGYGCPlviAIIT-LAVTEPGKGYLRPEACWLNWDMTkA 538
Cdd:cd15991   74 LHYFYMSTFAWMFVEGLHI-YRMLTEVRNI-NTGHMRFYYVVGWGIP---AIITgLAVGLDPQGYGNPDFCWLSVQDT-L 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 539 LLAFVVPALAIVVVNlitvTMVIIKTQRAAIGSSM-FQEVRAIVRICKNIAILTPLLGLTWGFGIATViNGHSLAFHIIF 617
Cdd:cd15991  148 IWSFAGPIGIVVIIN----TVIFVLAAKASCGRRQrYFEKSGVISMLRTAFLLLLLISATWLLGLMAV-NSDTLSFHYLF 222

                 ....*..
gi 134949047 618 SLLNALQ 624
Cdd:cd15991  223 AIFSCLQ 229
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
378-624 2.17e-10

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


Pssm-ID: 320655 [Multi-domain]  Cd Length: 293  Bit Score: 62.01  E-value: 2.17e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 378 SPVLTYItyIGLGISICSLIICLAIEVLVWSQVTKTEISYLRHLCIANIAATLLMadawfivasfLSGPVLHHNG--CVA 455
Cdd:cd15989    5 TPSVTLI--VGCGLSCLALITLAVVYAALWRYIRSERSIILINFCLSIISSNILI----------LVGQTQTHNKgiCTM 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 456 ATFFVHFFYLSVFFWMLAKAlliLYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAVTEPgKGYLRPEACWLNWDm 535
Cdd:cd15989   73 TTAFLHFFFLASFCWVLTEA---WQSYMAVTGKIRTRLIRKRFLCLGWGLPALVVAISMGFTKA-KGYGTPHYCWLSLE- 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 536 TKALLAFVVPALAIVVVNLITVTMV---------IIKTQRAAIGSSMFQEVRAIVRICKNIAILT--------------- 591
Cdd:cd15989  148 GGLLYAFVGPAAAVVLVNMVIGILVfnklvsrdgILDKKLKHRAGQMSEPHSGLTLKCAKCGVVSttalsattasnamas 227
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 134949047 592 --------PLLGLTWGFGIATVINGHSLAFHIIFSLLNALQ 624
Cdd:cd15989  228 lwsscvvlPLLALTWMSAVLAMTDKRSILFQILFAVFDSLQ 268
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
380-626 2.40e-10

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: 61.62  E-value: 2.40e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLAIEVLVwsqvtkTEISYLRHLCIANIAATLLMADA-WFIVASFLSGPVLHHNGCVAATF 458
Cdd:cd15263    3 VTTTIYFIGYSLSLVALSLALWIFLYF------KDLRCLRNTIHTNLMFTYILADLtWILTLTLQVSIGEDQKSCIILVV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 FVHFFYLSVFFWMLAKAlliLYGILIVFHTLPKSCLVASLF-SVGYGCPLVIAII-----TLAVTEPGKGY---LRPEAC 529
Cdd:cd15263   77 LLHYFHLTNFFWMFVEG---LYLYMLVVETFSGENIKLRVYaFIGWGIPAVVIVIwaivkALAPTAPNTALdpnGLLKHC 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 530 -WLNWDMTKALlaFVVPALAIVVVNLITVTM---VIIKTQRAAIGSSMFQEVRAivriCKNIAILTPLLGLTWGFGIATV 605
Cdd:cd15263  154 pWMAEHIVDWI--FQGPAILVLAVNLVFLVRimwVLITKLRSANTVETQQYRKA----AKALLVLIPLLGITYILVIAGP 227
                        250       260
                 ....*....|....*....|.
gi 134949047 606 INGhslAFHIIFSLLNALQVS 626
Cdd:cd15263  228 TEG---IAANIFEYVRAVLLS 245
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
380-624 5.62e-10

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: 60.58  E-value: 5.62e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIIClaIEVLVWSQVTKTEisylRHLCIANIAATLLMADAWFIVASFLSGPVLhhnGCVAATFF 459
Cdd:cd15436    3 LLFVITWVGIVISLVCLLIC--IFTFCFFRGLQTD----RNTIHKNLCINLFIAELLFLIGINRTQYTI---ACPIFAGL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 460 VHFFYLSVFFWMLAKALLILYGILIVFHTlpKSCLVASLFSVGYGCPLVIAIITLAVTEpgKGYLRPEACWLNWDmTKAL 539
Cdd:cd15436   74 LHFFFLAAFCWLCLEGVQLYLLLVEVFES--EYSRRKYFYLCGYSFPALVVAVSAAIDY--RSYGTEKACWLRVD-NYFI 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 540 LAFVVPALAIVVVNLITVTMVIIKTQRAAI----GSSMFQEVRAIVriCKNIAILTpLLGLTWGFGIaTVINGHSLAFHI 615
Cdd:cd15436  149 WSFIGPVTFVITLNLVFLVITLHKMVSHSDllkpDSSRLDNIKSWA--LGAIALLF-LLGLTWSFGL-MFINEESVVMAY 224

                 ....*....
gi 134949047 616 IFSLLNALQ 624
Cdd:cd15436  225 LFTIFNAFQ 233
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
381-624 6.70e-09

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: 57.16  E-value: 6.70e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYlrhlciANIAATLLMADAwfivaSFLSGPVLHHNG--CVAATF 458
Cdd:cd15993    4 LAIVTYSSVSASLAALVLTFSVLTCLRGLKSNTRGIH------SNIAAALFLSEL-----LFLLGINRTENQflCTVVAI 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 FVHFFYLSVFFWMLAKALLILYgilivFHTLPKSCLVASL---FSVGYGCPlviAIIT-LAVTEPGKGYLRPEACWLNwD 534
Cdd:cd15993   73 LLHYFFLSTFAWLFVQGLHIYR-----MQTEARNVNFGAMrfyYAIGWGVP---AIITgLAVGLDPEGYGNPDFCWIS-I 143
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 535 MTKALLAFVVPALAIVVVN----LITVTMVIIKTQRAAIGSSMFQEVRAIVrickniaILTPLLGLTWGFGIATViNGHS 610
Cdd:cd15993  144 HDKLVWSFAGPIVVVIVMNgvmfLLVARMSCSPGQKETKKTSVLMTLRSSF-------LLLLLISATWLFGLLAV-NNSV 215
                        250
                 ....*....|....
gi 134949047 611 LAFHIIFSLLNALQ 624
Cdd:cd15993  216 LAFHYLHAILCCLQ 229
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
380-623 2.75e-08

corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of 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, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320561 [Multi-domain]  Cd Length: 265  Bit Score: 55.33  E-value: 2.75e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 380 VLTYITYIGLGISICSLIICLAIEVLVWSqvtkteISYLRHLCIAN-IAATLLMADAWFIVASFLSGPVLHHN--GCVAA 456
Cdd:cd15445    3 IAVIINYLGHCISLVALLVAFVLFLRLRS------IRCLRNIIHWNlITAFILRNATWFVVQLTMSPEVHQSNvvWCRLV 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 457 TFFVHFFYLSVFFWMLAKALLILYGILIVFHTlpkSCLVASLF-SVGYGCPLVIaIITLAVtepGKGYLRPEACWLNwDM 535
Cdd:cd15445   77 TAAYNYFHVTNFFWMFGEGCYLHTAIVLTYST---DKLRKWMFiCIGWCIPFPI-IVAWAI---GKLYYDNEKCWFG-KR 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 536 TKALLAFVV--PALAIVVVNLI---TVTMVIIKTQRAAIGSSMFQEVRAIvricKNIAILTPLLGLTwgFGIATVINGHS 610
Cdd:cd15445  149 AGVYTDYIYqgPMILVLLINFIflfNIVRILMTKLRASTTSETIQYRKAV----KATLVLLPLLGIT--YMLFFVNPGED 222
                        250
                 ....*....|...
gi 134949047 611 LAFHIIFSLLNAL 623
Cdd:cd15445  223 EISRIVFIYFNSF 235
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
384-598 4.29e-07

corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of 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, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320392 [Multi-domain]  Cd Length: 265  Bit Score: 51.65  E-value: 4.29e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 384 ITYIGLGISICSLIICLAIEVLVWSqvtkteISYLRHLCIANIAATLLMADA-WFIVASFLSGPVLHHNGCVAATFFVHF 462
Cdd:cd15264    7 IYYLGFSISLVALAVALIIFLYFRS------LRCLRNNIHCNLIVTFILRNVtWFIMQNTLTEIHHQSNQWVCRLIVTVY 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 463 FYLSV--FFWMLAKAlliLYGILIVFHTLPKSCLVASLFSV-GYGCPLVIAIITLAVtepgKGYLRPEACWLN-WDMTKA 538
Cdd:cd15264   81 NYFQVtnFFWMFVEG---LYLHTMIVWAYSADKIRFWYYIViGWCIPCPFVLAWAIV----KLLYENEHCWLPkSENSYY 153
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 134949047 539 LLAFVVPALAIVVVNLI---TVTMVIIKTQRAAIGSSMFQEVRAIvricKNIAILTPLLGLTW 598
Cdd:cd15264  154 DYIYQGPILLVLLINFIflfNIVWVLITKLRASNTLETIQYRKAV----KATLVLLPLLGITY 212
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
381-624 6.46e-07

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: 51.34  E-value: 6.46e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLI--ICLAIEVLVWSQVTKTEISYLRHLciaNIAATLLMADAWFIVASfLSGPVLHHNGCVAATF 458
Cdd:cd15442    4 LVTISSAGCGVSMVFLIftIILYFFLRFTYQKFKSEDAPKIHV---NLSSSLLLLNLAFLLNS-GVSSRAHPGLCKALGG 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 FVHFFYLSVFFWMLAKALLILYGILIVF-----HTLPKSCLvaslfsVGYGCPLVIAIITLAVTEPGKGYLRPEA----- 528
Cdd:cd15442   80 VTHYFLLCCFTWMAIEAFHLYLLAIKVFntyihHYFAKLCL------VGWGFPALVVTITGSINSYGAYTIMDMAnrttl 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 529 --CWLNWDMTKALLAFVVPALAIV----VVNLITVTMVIIKTQRAAIGSSMFQEVRAIVRICKniaiLTPLLGLTWGFGI 602
Cdd:cd15442  154 hlCWINSKHLTVHYITVCGYFGLTflfnTVVLGLVAWKIFHLQSATAGKEKCQAWKGGLTVLG----LSCLLGVTWGLAF 229
                        250       260
                 ....*....|....*....|..
gi 134949047 603 ATVINGHSLAFHiIFSLLNALQ 624
Cdd:cd15442  230 FTYGSMSVPTVY-IFALLNSLQ 250
GPS smart00303
G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin ...
326-373 7.55e-07

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


Pssm-ID: 197639  Cd Length: 49  Bit Score: 46.23  E-value: 7.55e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 134949047   326 KSQCVGWHSLESRWDWRACKTIQENSRQAVCRCrpNKLyTSFSILMSP 373
Cdd:smart00303   2 NPICVFWDESSGEWSTRGCELLETNGTHTTCSC--NHL-TTFAVLMDV 46
GPS pfam01825
GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for ...
328-370 1.09e-06

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


Pssm-ID: 460350  Cd Length: 44  Bit Score: 45.76  E-value: 1.09e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 134949047  328 QCVGW---HSLESRWDWRACKTIQENSRQAVCRCrpNKLyTSFSIL 370
Cdd:pfam01825   2 QCVFWdftNSTTGRWSTEGCTTVSLNDTHTVCSC--NHL-TSFAVL 44
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
381-624 3.61e-05

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: 45.90  E-value: 3.61e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLIICLAIEVLVWSQVTKTEISYlrHLciaNIAATLLMADAWFIVASFLSGPVLHhNGCVAATFFV 460
Cdd:cd15443    4 LTYISIVGCSISAAASLLTILLHFFSRKQPKDSTTRI--HM---NLLGSLFLLNGSFLLSPPLATSQST-WLCRAAAALL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 461 HFFYLSVFFWMLAKALLiLYGILIVFHTLPKSCLVASLFSVGYGCPLVIAIITLAV---------TEPGKGYLRPEACWL 531
Cdd:cd15443   78 HYSLLCCLTWMAIEGFH-LYLLLVKVYNIYIRRYVLKLCVLGWGLPALIVLLVLIFkreaygphtIPTGTGYQNASMCWI 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 532 NwdmTKALLAFVVPALAIVVVNLITVTMVIIKTQRAAIGSsmfQEVRAIVRICKNIAI---LTPLLGLTWGFGIATVinG 608
Cdd:cd15443  157 T---SSKVHYVLVLGYAGLTSLFNLVVLAWVVRMLRRLRS---RKQELGERARRDWVTvlgLTCLLGTTWALAFFSF--G 228
                        250
                 ....*....|....*..
gi 134949047 609 HSLAFHII-FSLLNALQ 624
Cdd:cd15443  229 VFLIPQLFlFTIINSLY 245
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
453-620 4.25e-05

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: 45.44  E-value: 4.25e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 453 CVAATFFVHFFYLSVFFWMLAKAllilYGILIVFHTLPKSCL-----------VASLFSVGYGCPLVIAIITLAVTEpgK 521
Cdd:cd15259   70 CQAVGILLHYSTLCTLLWVGVTA----RNMYKQVTKTAKPPQdedqpprppkpMLRFYLIGWGIPLIICGITAAVNL--D 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 522 GYLRPEACWLNWDMTkaLLAFVVPALAIVVVNLITV--TMVIIKTQRAAIGSsmfqEVRAIVRICKNIAIltpllglTWG 599
Cdd:cd15259  144 NYSTYDYCWLAWDPS--LGAFYGPAALIVLVNCIYFlrIYCQLKGAPVSFQS----QLRGAVITLFLYVA-------MWA 210
                        170       180
                 ....*....|....*....|.
gi 134949047 600 FGIATVINGHSLafHIIFSLL 620
Cdd:cd15259  211 CGALAVSQRYFL--DLVFSCL 229
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
381-626 1.26e-04

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: 44.04  E-value: 1.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 381 LTYITYIGLGISICSLIIC-LAIEVLVWSQVTKTEIsylrhlcIANIAATLLMADAWFIVA-SFLSGPVLhhngCVAATF 458
Cdd:cd15992    4 LKTLTWSSVGVTLGFLLLTfLFLLCLRALRSNKTSI-------RKNGATALFLSELVFILGiNQADNPFA----CTVIAI 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 459 FVHFFYLSVFFWMLAKALLIlYGILIVFHTLPKSCLvASLFSVGYGCPlviAIIT-LAVTEPGKGYLRPEACWLNWDMTk 537
Cdd:cd15992   73 LLHFFYLCTFSWLFLEGLHI-YRMLSEVRDINYGPM-RFYYLIGWGVP---AFITgLAVGLDPEGYGNPDFCWLSIYDT- 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 538 ALLAFVVPALAIVVVNLITVTMviikTQRA--AIGSSMFQEVRAIVRICKNIAILTPLLGLTWGFGIATViNGHSLAFHI 615
Cdd:cd15992  147 LIWSFAGPVAFAVSMNVFLYIL----SSRAscSAQQQSFEKKKGPVSGLRTAFTVLLLVSVTCLLALLSV-NSDVILFHY 221
                        250
                 ....*....|.
gi 134949047 616 IFSLLNALQVS 626
Cdd:cd15992  222 LFAGFNCLQGP 232
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
383-597 1.88e-04

The pigment dispersing factor receptor, member of the class B seven-transmembrane G protein-coupled receptors; The pigment dispersing factor receptor (PDFR) is a G protein-coupled receptor that binds the circadian clock neuropeptide PDF, a functional ortholog of the mammalian vasoactive intestinal peptide (VIP), on the pacemaker neurons. The PDFR is implicated in regulating flight circuit development and in modulating acute flight In Drosophila melanogaster. The PDFR activation stimulates adenylate cyclase, thereby increasing cAMP levels in many different pacemakers, and the receptor signaling has been shown to regulate behavioral circadian rhythms and geotaxis in Drosophila. The PDFR belongs to the B1 subfamily of class B GPCRs, also referred to as secretin-like receptor family, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), calcitonin gene-related peptide, parathyroid hormone (PTH), and corticotropin-releasing factor. . These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. They play key roles in hormone homeostasis in mammals 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).


Pssm-ID: 320389 [Multi-domain]  Cd Length: 282  Bit Score: 43.90  E-value: 1.88e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 383 YITYIGLGISICSLIICLAIEVLVWS-QVTKTEISylRHLCIANIAATL----LMADAWFIV-------ASFLSGPVLHH 450
Cdd:cd15261    6 TLEIVGLCLSLVSLIISLFIFSYFRTlRNHRTRIH--KNLFLAILLQVIirlvLYIDQAITRsrgshtnAATTEGRTINS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 451 NG--CVAATFFVHFFYLSVFFWMLAKALLiLYGILIV--FHTLPKSCLvasLFSVGYGCPLVIAIITLAVTEPgkgYLRP 526
Cdd:cd15261   84 TPilCEGFYVLLEYAKTVMFMWMFIEGLY-LHNIIVVsvFSGKPNYLF---YYILGWGIPIVHTSAWAIVTLI---KMKV 156
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 134949047 527 EACWLNWDMTKALLAFVVPALAIVVVNLITVtMVIIKTQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLT 597
Cdd:cd15261  157 NRCWFGYYLTPYYWILEGPRLAVILINLFFL-LNIIRVLVSKLRESHSREIEQVRKAVKAAIVLLPLLGIT 226
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
384-598 3.16e-04

corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; The vertebrate corticotropin-releasing factor (CRF) receptors are predominantly expressed in central nervous system with high levels in cortex tissue, brain stem, and pituitary. They have two isoforms as a result of alternative splicing of the same receptor gene: CRF-R1 and CRF-R2, which differ in tissue distribution and ligand binding affinities. Recently, a third CRF receptor (CRF-R3) has been identified in catfish pituitary. The catfish CRF-R1 is highly homologous to CRF-R3. CRF is a 41-amino acid neuropeptide that plays a central role in coordinating neuroendocrine, behavioral, and autonomic responses to stress by acting as the primary neuroregulator of the hypothalamic-pituitary-adrenal axis, which controls the levels of cortisol and other stress related hormones. In addition, the CRF family of neuropeptides also includes structurally related peptides such as mammalian urocortin, fish urotensin I, and frog sauvagine. The actions of CRF and CRF-related peptides are mediated through specific binding to CRF-R1 and CRF-R2. CRF and urocortin 1 bind and activate mammalian CRF-R1 with similar high affinities. By contrast, urocortin 2 and urocortin 3 do not bind to CRF-R1 or stimulate CRF-R1-mediated cAMP formation. Urocortin 1 also shows high affinity for mammalian CRF-R2, whereas CRF has significantly lower affinity for this receptor. These evidence suggest that urocortin 1 is an endogenous ligand for CRF-R1 and CRF-R2. The CRF receptors are members of 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, and parathyroid hormone (PTH). These receptors contain the large N-terminal extracellular domain (ECD), which plays a critical role in hormone recognition by binding to the C-terminal portion of the peptide. On the other hand, the N-terminal segment of the hormone induces receptor activation by interacting with the receptor transmembrane domains and connecting extracellular loops, triggering intracellular signaling pathways. All members of the B1 subfamily preferentially couple to G proteins of G(s) family, which positively stimulate adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. However, depending on its cellular location and function, CRF receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320562 [Multi-domain]  Cd Length: 264  Bit Score: 43.02  E-value: 3.16e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 384 ITYIGLGISICSLIICLAIEVLVWSqvtkteISYLRHLCIANIAATLLMADAWFIVASFLSGPVLHHNG--CVAATFFVH 461
Cdd:cd15446    7 INYLGHCISVGALVVAFLLFLCLRS------IRCLRNIIHWNLITTFILRNVMWFLLQMIDHNIHESNEvwCRCITTIYN 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 462 FFYLSVFFWMLAKALLILYGILIVFHTLP-KSCLvasLFSVGYGCPLVIaIITLAVtepGKGYLRPEACWLNWDMTKAL- 539
Cdd:cd15446   81 YFVVTNFFWMFVEGCYLHTAIVMTYSTDKlRKWV---FLFIGWCIPCPI-IVAWAI---GKLYYENEQCWFGKEPGKYId 153
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 134949047 540 ---LAFVVPALAIVVVNLITVTMVIIKTQRAAIGSSMFQEVRAIvricKNIAILTPLLGLTW 598
Cdd:cd15446  154 yiyQGPVILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAV----KATLVLLPLLGITY 211
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
384-534 1.17e-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: 41.32  E-value: 1.17e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 384 ITYIGLGISICSLiiCLAIEVLVWSQVTKTEISYLRhlcIANIAATLLMADAWFIVASFL-SGPVLHH-----NGCVAAT 457
Cdd:cd15270    7 IYTVGYSISIVSL--CVAVAILVAFRRLHCPRNYIH---IQLFFTFILKAIAVFIKDAALfQEDDTDHcsmstVLCKVSV 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 458 FFVHFFYLSVFFWMLAKALLIlygilivfhtlpkSCLVASLFS-----------VGYGCPLVIAIITLAVtepgKGYLRP 526
Cdd:cd15270   82 VFCHYCVMTNFFWLLVEAVYL-------------NCLLASSFPrgkryfwwlvlLGWGLPTLCTGTWILC----KLYFED 144

                 ....*....
gi 134949047 527 EACW-LNWD 534
Cdd:cd15270  145 TECWdINND 153
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
452-598 2.14e-03

parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone (PTH) receptor family has three subtypes: PTH1R, PTH2R and PTH3R. PTH1R is expressed in bone and kidney and is activated by two polypeptide ligands: PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, and PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH1R couples predominantly to G(s)-protein that in turn activates adenylate cyclase thereby producing cAMP, but it can also couple to several G protein subtypes, including G(q/11), G(i/o), and G(12/13), resulting in activation of multiple intracellular signaling pathways. PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. PTH3R is found in chicken and fish, but it is absent in mammals. The PTH receptors are members of the B1 (or secretin-like) subfamily of class B GPCRs, which include receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, glucagon, glucagon-like peptide (GLP), and calcitonin gene-related peptide. 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.


Pssm-ID: 320650 [Multi-domain]  Cd Length: 290  Bit Score: 40.70  E-value: 2.14e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 452 GC-VAATFFVHFFYLSvFFWMLAKALLILYGILIVFHTLPKSCLVASLFsvGYGCPLVIAIITLAVtepgKGYLRPEACw 530
Cdd:cd15984   94 GCkVAVTFFLYFLATN-YYWILVEGLYLHSLIFMAFFSEKKYLWGFTLF--GWGLPAVFVTIWASV----RATLADTGC- 165
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 134949047 531 lnWDMTKALLAFV--VPALAIVVVNLITVTMVI--IKTQRAAIGSSMFQEVRAIVRICKNIAILTPLLGLTW 598
Cdd:cd15984  166 --WDLSAGNLKWIiqVPILAAIVVNFILFINIVrvLATKLRETNAGRCDTRQQYRKLLKSTLVLMPLFGVHY 235
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
452-596 9.94e-03

growth-hormone-releasing hormone receptor type 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Growth hormone-releasing hormone receptor type 2 (GHRHR2) is found in non-mammalian vertebrates such as chicken and frog. It 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), vasoactive intestinal peptide, and mammalian growth hormone-releasing hormone. 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. Mammalian 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. Mammalian 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: 320399 [Multi-domain]  Cd Length: 267  Bit Score: 38.17  E-value: 9.94e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 134949047 452 GCVAATFFVHFFYLSVFFWMLAKALLILYGILIVFHTLPKSCLVASLfsVGYGCPLVIaIITLAVTepgKGYLRPEACWl 531
Cdd:cd15271   76 ACKAAVTFFQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYIL--IGWGAPSVT-VTVWVLT---RLQYDNRGCW- 148
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 134949047 532 nwDMTKALLAFVV--PALAIVVVNLI----TVTMVIIKTQRAAIGSSMFQEVRaivRICKNIAILTPLLGL 596
Cdd:cd15271  149 --DDLESRIWWIIktPILLSVFVNFLifinVIRILVQKLKSPDVGGNDTSHYM---RLAKSTLLLIPLFGV 214
 
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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