NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|530384486|ref|XP_005249675|]
View 

pituitary adenylate cyclase-activating polypeptide type I receptor isoform X6 [Homo sapiens]

Protein Classification

hormone receptor( domain architecture ID 12039880)

hormone receptor is a class B G-protein coupled receptor (GPCR) for hormones and/or hormone-related peptides; contains a large N-terminal extracellular domain that plays a critical role in peptide hormone recognition; GPCRs transmit physiological signals from the outside of the cell to the inside via G proteins by binding to an extracellular agonist, which induces conformational changes that lead to the activation of heterotrimeric G proteins, which then bind to and activate numerous downstream effector proteins

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
93-360 0e+00

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


:

Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 533.01  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAV 172
Cdd:cd15987    1 YLSVKALYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQDSDHCFVSTVECKAV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALWWVI 252
Cdd:cd15987   81 MVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLRLHFDDTGCWDMNDNTALWWVI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 332
Cdd:cd15987  161 KGPVVGSIMINFVLFIGIIIILVQKLQSPDIGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 240
                        250       260
                 ....*....|....*....|....*...
gi 530384486 333 SFQGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15987  241 SFQGFVVAVLYCFLNGEVQSEIKRKWRS 268
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
46-80 4.32e-07

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


:

Pssm-ID: 397086  Cd Length: 64  Bit Score: 46.59  E-value: 4.32e-07
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 530384486   46 GFNDSSPDmGVVSRNCTEDG-WSEPFPHYFDACGFD 80
Cdd:pfam02793  30 YFSGFDPR-GNASRNCTEDGtWSEHPPSNYSNCTSN 64
 
Name Accession Description Interval E-value
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
93-360 0e+00

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


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 533.01  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAV 172
Cdd:cd15987    1 YLSVKALYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQDSDHCFVSTVECKAV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALWWVI 252
Cdd:cd15987   81 MVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLRLHFDDTGCWDMNDNTALWWVI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 332
Cdd:cd15987  161 KGPVVGSIMINFVLFIGIIIILVQKLQSPDIGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 240
                        250       260
                 ....*....|....*....|....*...
gi 530384486 333 SFQGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15987  241 SFQGFVVAVLYCFLNGEVQSEIKRKWRS 268
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
93-339 5.91e-115

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: 335.79  E-value: 5.91e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486   93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCfiSTVECKAV 172
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLDHC--SWVGCKVV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWDMNDsTALWW 250
Cdd:pfam00002  79 AVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCWLSNE-NGLWW 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  251 VIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYT--VFAFSPENVSKRERLVFE 328
Cdd:pfam00002 158 IIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYRRLAKSTLLLLPLLGITWVfgLFAFNPENTLRVVFLYLF 237
                         250
                  ....*....|.
gi 530384486  329 LGLGSFQGFVV 339
Cdd:pfam00002 238 LILNSFQGFFV 248
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
46-80 4.32e-07

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


Pssm-ID: 397086  Cd Length: 64  Bit Score: 46.59  E-value: 4.32e-07
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 530384486   46 GFNDSSPDmGVVSRNCTEDG-WSEPFPHYFDACGFD 80
Cdd:pfam02793  30 YFSGFDPR-GNASRNCTEDGtWSEHPPSNYSNCTSN 64
HormR smart00008
Domain present in hormone receptors;
46-86 2.78e-06

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 44.81  E-value: 2.78e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 530384486    46 GFNDSSPDmGVVSRNCTEDG-WSEPFPhYFDACGFDEYESET 86
Cdd:smart00008  31 YFSGFSYK-TGASRNCTENGgWSPPFP-NYSNCTSNDYEELK 70
 
Name Accession Description Interval E-value
7tmB1_PACAP-R1 cd15987
pituitary adenylate cyclase-activating polypeptide type 1 receptor, member of the class B ...
93-360 0e+00

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


Pssm-ID: 320653 [Multi-domain]  Cd Length: 268  Bit Score: 533.01  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAV 172
Cdd:cd15987    1 YLSVKALYTVGYSTSLVSLTTAMVILCRFRKLHCTRNFIHMNLFVSFILRAISVFIKDGVLYAEQDSDHCFVSTVECKAV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALWWVI 252
Cdd:cd15987   81 MVFFHYCVMSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTICVTVWAVLRLHFDDTGCWDMNDNTALWWVI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 332
Cdd:cd15987  161 KGPVVGSIMINFVLFIGIIIILVQKLQSPDIGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 240
                        250       260
                 ....*....|....*....|....*...
gi 530384486 333 SFQGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15987  241 SFQGFVVAVLYCFLNGEVQSEIKRKWRS 268
7tmB1_Secretin_R-like cd15930
secretin receptor-like group of hormone receptors, member of the class B family of ...
93-360 2.35e-173

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


Pssm-ID: 320596 [Multi-domain]  Cd Length: 268  Bit Score: 484.63  E-value: 2.35e-173
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAV 172
Cdd:cd15930    1 YLTVKIIYTVGYSLSLTSLTTAMIILCLFRKLHCTRNYIHMNLFVSFILRAIAVFIKDAVLFSSEDVDHCFVSTVGCKAS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALWWVI 252
Cdd:cd15930   81 MVFFQYCVMANFFWLLVEGLYLHTLLVISFFSERRYFWWYVLIGWGAPTVFVTVWIVARLYFEDTGCWDINDESPYWWII 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 332
Cdd:cd15930  161 KGPILISILVNFVLFINIIRILLQKLRSPDIGGNESSQYKRLARSTLLLIPLFGIHYIVFAFFPENISLGIRLYFELCLG 240
                        250       260
                 ....*....|....*....|....*...
gi 530384486 333 SFQGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15930  241 SFQGFVVAVLYCFLNGEVQAEIKRKWRS 268
7tmB1_GHRHR2 cd15271
growth-hormone-releasing hormone receptor type 2, member of the class B family of ...
93-360 1.56e-135

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: 388.70  E-value: 1.56e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAV 172
Cdd:cd15271    1 FSTVKLLYTVGYGTSLTSLITAVLIFCTFRKLHCTRNYIHINLFVSFILRALAVFIKDAVLFADESVDHCTMSTVACKAA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDmNDSTALWWVI 252
Cdd:cd15271   81 VTFFQFCVLANFFWLLVEGMYLQTLLLLTFTSDRKYFWWYILIGWGAPSVTVTVWVLTRLQYDNRGCWD-DLESRIWWII 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 332
Cdd:cd15271  160 KTPILLSVFVNFLIFINVIRILVQKLKSPDVGGNDTSHYMRLAKSTLLLIPLFGVHYVVFAFFPEHVGVEARLYFELVLG 239
                        250       260
                 ....*....|....*....|....*...
gi 530384486 333 SFQGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15271  240 SFQGFIVALLYCFLNGEVQAEIKKRLGK 267
7tmB1_VIP-R1 cd15269
vasoactive intestinal polypeptide (VIP) receptor 1, member of the class B family of ...
93-359 2.28e-134

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


Pssm-ID: 320397 [Multi-domain]  Cd Length: 268  Bit Score: 386.13  E-value: 2.28e-134
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAV 172
Cdd:cd15269    1 FGTVKTGYTIGHSLSLISLTAAMIILCLFRKLHCTRNYIHMHLFMSFILRAIAVFIKDAVLFESGEEDHCSVASVGCKAA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALWWVI 252
Cdd:cd15269   81 MVFFQYCIMANFFWLLVEGLYLHTLLAVSFFSERKYFWWYILIGWGAPSVFITAWSVARIYFEDVGCWDTIIESLLWWII 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 332
Cdd:cd15269  161 KTPILVSILVNFILFICIIRILVQKLHSPDIGRNESSQYSRLAKSTLLLIPLFGIHYIMFAFFPDNFKAEVKLVFELILG 240
                        250       260
                 ....*....|....*....|....*..
gi 530384486 333 SFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15269  241 SFQGFVVAVLYCFLNGEVQAELKRKWR 267
7tmB1_secretin cd15275
secretin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
93-359 1.09e-129

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


Pssm-ID: 320403 [Multi-domain]  Cd Length: 271  Bit Score: 374.08  E-value: 1.09e-129
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAV 172
Cdd:cd15275    1 FMYLKTMYTVGYSVSLVSLAIALAILCSFRRLHCTRNYIHMQLFLSFILRAISIFIKDAVLFSSEDDNHCDIYTVGCKVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALWWVI 252
Cdd:cd15275   81 MVFSNYCIMANYSWLLVEGLYLHSLLSISFFSERKHLWWYIALGWGSPLIFIISWAIARYLHENEGCWDTRRNAWIWWII 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRE---RLVFEL 329
Cdd:cd15275  161 RGPVILSIFVNFILFLNILRILMRKLRAPDMRGNEFSQYKRLAKSTLLLIPLFGLHYILFAFFPEDVSSGTmeiWLFFEL 240
                        250       260       270
                 ....*....|....*....|....*....|
gi 530384486 330 GLGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15275  241 ALGSFQGFVVAVLYCFLNGEVQLEIQRKWR 270
7tmB1_VIP-R2 cd15986
vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of ...
93-360 2.44e-122

vasoactive intestinal polypeptide (VIP) receptor 2, member of the class B family of seven-transmembrane G protein-coupled receptors; Vasoactive intestinal peptide (VIP) receptor 2 is a member of the group of G protein-coupled receptors for structurally similar peptide hormones that also include secretin, growth-hormone-releasing hormone (GHRH), and pituitary adenylate cyclase activating polypeptide (PACAP). These receptors are classified into the subfamily B1 of class B GRCRs that consists of the classical hormone receptors and have been identified in all the vertebrates, from fishes to mammals, but are not present in plants, fungi, or prokaryotes. For all class B receptors, the large N-terminal extracellular domain plays a critical role in peptide hormone recognition. VIP and PACAP exert their effects through three G protein-coupled receptors, PACAP-R1, VIP-R1 (vasoactive intestinal receptor type 1, also known as VPAC1) and VIP-R2 (or VPAC2). PACAP-R1 binds only PACAP with high affinity, whereas VIP-R1 and -R2 specifically bind and respond to both VIP and PACAP. VIP and PACAP and their receptors are widely expressed in the brain and periphery. They are upregulated in neurons and immune cells in responses to CNS injury and/or inflammation and exert potent anti-inflammatory effects, as well as play important roles in the control of circadian rhythms and stress responses, among many others. VIP-R1 is preferentially coupled to a stimulatory G(s) protein, which leads to the activation of adenylate cyclase and thereby increases in intracellular cAMP level. However, depending on its cellular location, VIP-R1 is also capable of coupling to additional G proteins such as G(q) protein, thus leading to the activation of phospholipase C and intracellular calcium influx.


Pssm-ID: 320652 [Multi-domain]  Cd Length: 269  Bit Score: 355.27  E-value: 2.44e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFI--STVECK 170
Cdd:cd15986    1 YIVVKTIYTLGHSVSLIALTTGSTILCLFRKLHCTRNYIHLNLFFSFILRAISVLVKDDILYSSSNTEHCTVppSLIGCK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 171 AVMVFFHYCVVSNYFWLFIEGLYLFTLLVeTFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALWW 250
Cdd:cd15986   81 VSLVILQYCIMANFYWLLVEGLYLHTLLV-VIFSENRHFIVYLLIGWGIPTVFIIAWIVARIYLEDTGCWDTNDHSVPWW 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 251 VIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELG 330
Cdd:cd15986  160 VIRIPIIISIILNFILFISIIRILLQKLRSPDVGGNDQSQYKRLAKSTLLLIPLFGVHYIVFVYFPDSSSSNYQIFFELC 239
                        250       260       270
                 ....*....|....*....|....*....|
gi 530384486 331 LGSFQGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15986  240 LGSFQGLVVAILYCFLNSEVQGELKRKWRS 269
7tmB1_GHRHR cd15270
growth-hormone-releasing hormone receptor, member of the class B family of seven-transmembrane ...
93-358 1.17e-119

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: 348.71  E-value: 1.17e-119
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVECKAV 172
Cdd:cd15270    1 FSTVKIIYTVGYSISIVSLCVAVAILVAFRRLHCPRNYIHIQLFFTFILKAIAVFIKDAALFQEDDTDHCSMSTVLCKVS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALWWVI 252
Cdd:cd15270   81 VVFCHYCVMTNFFWLLVEAVYLNCLLASSFPRGKRYFWWLVLLGWGLPTLCTGTWILCKLYFEDTECWDINNDSPYWWII 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGLG 332
Cdd:cd15270  161 KGPIVISVGVNFLLFLNIIRILLKKLDPRQINFNNSAQYRRLSKSTLLLIPLFGTHYIIFNFLPDYAGLGIRLYLELCLG 240
                        250       260
                 ....*....|....*....|....*.
gi 530384486 333 SFQGFVVAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15270  241 SFQGFIVAVLYCFLNQEVQTEISRKW 266
7tm_2 pfam00002
7 transmembrane receptor (Secretin family); This family is known as Family B, the ...
93-339 5.91e-115

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: 335.79  E-value: 5.91e-115
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486   93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCfiSTVECKAV 172
Cdd:pfam00002   1 ALSLKVIYTVGYSLSLVALLLAIAIFLLFRKLHCTRNYIHLNLFASFILRALLFLVGDAVLFNKQDLDHC--SWVGCKVV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWDMNDsTALWW 250
Cdd:pfam00002  79 AVFLHYFFLANFFWMLVEGLYLYTLLVEVFFSERKYFWWYLLIGWGVPALVVGIWAGVdpKGYGEDDGCWLSNE-NGLWW 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  251 VIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYT--VFAFSPENVSKRERLVFE 328
Cdd:pfam00002 158 IIRGPILLIILVNFIIFINIVRILVQKLRETNMGKSDLKQYRRLAKSTLLLLPLLGITWVfgLFAFNPENTLRVVFLYLF 237
                         250
                  ....*....|.
gi 530384486  329 LGLGSFQGFVV 339
Cdd:pfam00002 238 LILNSFQGFFV 248
7tmB1_PTHR cd15265
parathyroid hormone receptors, member of the class B family of seven-transmembrane G ...
99-358 3.04e-104

parathyroid hormone receptors, 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 a 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. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39), but not by PTHrP. PTH also strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs, suggesting that TIP-39 is a natural ligand for PTH2R. On the other hand, PTH3R binds and responds to both PTH and PTHrP, but not the TIP-39. Moreover, the PTH3R is more closely related to the PTH1R than PTH2R. PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. The 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: 320393 [Multi-domain]  Cd Length: 289  Bit Score: 310.08  E-value: 3.04e-104
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  99 LYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILY-------AEQDSNHCFISTVE--- 168
Cdd:cd15265    7 IYTVGYSISLVSLTVAVFILGYFRRLHCTRNYIHMHLFVSFMLRAVSIFVKDAVLYsgsgldeLERPSMEDLKSIVEapp 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 --------CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCW 240
Cdd:cd15265   87 vdksqyvgCKVAVTLFLYFLATNYYWILVEGLYLHSLIFMAFFSDKKYLWGFTLIGWGFPAVFVIPWASVRATLADTRCW 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 241 DMNDsTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNE-SSIYLRLARSTLLLIPLFGIHYTVFAFSPENV 319
Cdd:cd15265  167 DLSA-GNYKWIYQVPILAAIVVNFILFLNIVRVLATKLRETNAGRCDtRQQYRKLAKSTLVLIPLFGVHYIVFMGMPYTE 245
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 530384486 320 S---KRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15265  246 VgllWQIRMHYELFFNSFQGFFVAIIYCFCNGEVQAEIKKRW 287
7tmB1_GlucagonR-like cd15929
glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G ...
93-358 1.13e-98

glucagon receptor-like subfamily, member of the class B family of seven-transmembrane G protein-coupled receptors; This group represents the glucagon receptor family of G protein-coupled receptors, which includes glucagon receptor (GCGR), glucagon-like peptide-1 receptor (GLP1R), GLP2R, and closely related receptors. These receptors are activated by the members of the glucagon (GCG) peptide family including GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from the large proglucagon precursor. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. Receptors in this group belong to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, 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. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 341353 [Multi-domain]  Cd Length: 279  Bit Score: 295.50  E-value: 1.13e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILY------AEQDSNHCFIS- 165
Cdd:cd15929    1 LSSLQVMYTVGYSLSLAALVLALAILLGLRKLHCTRNYIHANLFASFILRALSVLVKDALLPrrysqkGDQDLWSTLLSn 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 166 --TVECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMN 243
Cdd:cd15929   81 qaSLGCRVAQVLMQYCVAANYYWLLVEGLYLHTLLVLAVFSERSIFRLYLLLGWGAPVLFVVPWGIVKYLYENTGCWTRN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 244 DSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGgnESSIYLRLARSTLLLIPLFGIHYTVFAFSPEN----V 319
Cdd:cd15929  161 DNMAYWWIIRLPILLAILINFFIFVRILKILVSKLRANQMC--KTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEqargT 238
                        250       260       270
                 ....*....|....*....|....*....|....*....
gi 530384486 320 SKRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15929  239 LRFIKLFFELFLSSFQGLLVAVLYCFANKEVQSELRKKW 277
7tmB1_hormone_R cd15041
The subfamily B1 of hormone receptors (secretin-like), member of the class B family ...
93-359 2.42e-98

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: 294.52  E-value: 2.42e-98
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFIST-----V 167
Cdd:cd15041    1 LLVVYYIYLVGYSLSLVALLPAIVIFLYFRSLRCTRIRLHINLFLSFILRAVFWIIWDLLVVYDRLTSSGVETVlmqnpV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 168 ECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTA 247
Cdd:cd15041   81 GCKLLSVLKRYFKSANYFWMLCEGLYLHRLIVVAFFSEPSSLKLYYAIGWGLPLVIVVIWAIVRALLSNESCWISYNNGH 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 248 LWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMggNESSIYLRLARSTLLLIPLFGIHYTVFAFSPEN--VSKRERL 325
Cdd:cd15041  161 YEWILYGPNLLALLVNLFFLINILRILLTKLRSHPN--AEPSNYRKAVKATLILIPLFGIQYLLTIYRPPDgsEGELVYE 238
                        250       260       270
                 ....*....|....*....|....*....|....
gi 530384486 326 VFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15041  239 YFNAILNSSQGFFVAVIYCFLNGEVQSELKRKWS 272
7tmB1_PTH-R_related cd15272
invertebrate parathyroid hormone-related receptors, member of the class B family of ...
95-359 3.55e-92

invertebrate parathyroid hormone-related receptors, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes parathyroid hormone (PTH)-related receptors found in invertebrates such as mollusks and annelid worms. The PTH family receptors are members of the B1 subfamily of class B GPCRs, which includes 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. The parathyroid hormone type 1 receptor (PTH1R) is found in all vertebrate species and is activated by two polypeptide ligands: parathyroid hormone (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 adenylyl 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 signaling pathways.


Pssm-ID: 320400 [Multi-domain]  Cd Length: 285  Bit Score: 279.27  E-value: 3.55e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  95 SVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKD----------WILYAEQDSNHCFI 164
Cdd:cd15272    3 SIRLMYNIGYGLSLVSLLIAVIIMLYFKKLHCPRNTIHINLFVSFILRAVLSFIKEnllvqgvgfpGDVYYDSNGVIEFK 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 165 STV---ECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWD 241
Cdd:cd15272   83 DEGshwECKLFFTMFNYILGANYMWIFVEGLYLHMLIFVAVFSENSRVKWYILLGWLSPLLFVLPWVFVRATLEDTLCWN 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 242 MNDSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSK 321
Cdd:cd15272  163 TNTNKGYFWIIRGPIVISIAINFLFFINIVRVLFTKLKASNTQESRPFRYRKLAKSTLVLIPLFGVHYMVFVVLPDSMSS 242
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 530384486 322 RE----RLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15272  243 DEaelvWLYFEMFFNSFQGFIVALLFCFLNGEVQSEIKKKWQ 284
7tmB1_GLP2R cd15266
glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G ...
94-359 6.57e-92

glucagon-like peptide-2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon-like peptide-2 receptor (GLP2R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor (GCGR) and GLP1R. GLP2R is activated by glucagon-like peptide 2, which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. GLP2R belongs to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, 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. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320394 [Multi-domain]  Cd Length: 280  Bit Score: 278.17  E-value: 6.57e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  94 LSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKD----------------WILYAEQ 157
Cdd:cd15266    2 LTLQLIYTIGYSLSLISLSLALLILLLLRKLHCTRNYIHMNLFASFILRALAVLIKDivlystyskrpddetgWISYLSE 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 158 dsnhcfISTVECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDT 237
Cdd:cd15266   82 ------ESSTSCRVAQVFMHYFVGANYFWLLVEGLYLHTLLVTAVLSERRLLKKYMLIGWGTPVLFVVPWGVAKILLENT 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 238 GCWDMNDSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSiyLRLARSTLLLIPLFGIHYTVFAFSP- 316
Cdd:cd15266  156 GCWGRNENMGIWWIIRGPILLCITVNFYIFLKILKLLLSKLKAQQMRFTDYK--YRLARSTLVLIPLLGIHEVVFSFITd 233
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*.
gi 530384486 317 ---ENVSKRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15266  234 eqvEGFSRHIRLFIQLTLSSFQGFLVAVLYCFANGEVKAELKKRWQ 279
7tmB1_PTH1R cd15984
parathyroid hormone 1 receptor, member of the class B family of seven-transmembrane G ...
99-358 1.55e-84

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: 259.88  E-value: 1.55e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  99 LYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVE---------- 168
Cdd:cd15984    7 IYTVGYSISLGSLTVAVLILGYFRRLHCTRNYIHMHLFLSFMLRAVSIFVKDAVLYSGSALEEMERITEEdlksiteapp 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 --------CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCW 240
Cdd:cd15984   87 adkaqfvgCKVAVTFFLYFLATNYYWILVEGLYLHSLIFMAFFSEKKYLWGFTLFGWGLPAVFVTIWASVRATLADTGCW 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 241 DMNdSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNES-SIYLRLARSTLLLIPLFGIHYTVFAFSP--- 316
Cdd:cd15984  167 DLS-AGNLKWIIQVPILAAIVVNFILFINIVRVLATKLRETNAGRCDTrQQYRKLLKSTLVLMPLFGVHYIVFMAMPyte 245
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 530384486 317 -ENVSKRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15984  246 vSGILWQVQMHYEMLFNSFQGFFVAIIYCFCNGEVQAEIKKSW 288
7tmB1_GCGR cd15267
glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled ...
92-359 7.89e-81

glucagon receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon receptor (GCGR) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon-like peptide-1 receptor (GLP1R) and GLP2R. GCGR is activated by glucagon, which is derived from the large proglucagon precursor. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR belongs to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, 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. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320395 [Multi-domain]  Cd Length: 281  Bit Score: 250.12  E-value: 7.89e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  92 YYLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWIL---YAEQDSNHCFISTVE 168
Cdd:cd15267    2 TYSSFQVMYTVGYSLSLGALLLALAILGGFSKLHCMRNAIHMNLFASFILKASSVLVIDGLLrtrYSQKIEDDLSSTWLS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 ------CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDM 242
Cdd:cd15267   82 deavagCRVAAVFMQYGIVANYCWLLVEGIYLHNLLVLAVFPERSYFSLYLCIGWGAPALFVVPWVVVKCLYENVQCWTS 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 243 NDSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMggNESSIYLRLARSTLLLIPLFGIHYTVFAF----SPEN 318
Cdd:cd15267  162 NDNMGFWWILRFPVFLAILINFFIFVRIIQILVSKLRARQM--HYTDYKFRLAKSTLTLIPLLGIHEVVFAFvtdeHAQG 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|.
gi 530384486 319 VSKRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15267  240 TLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWH 280
7tmB1_GlucagonR-like_1 cd15985
uncharacterized group of glucagon receptor-like proteins, member of the class B family of ...
94-359 4.80e-80

uncharacterized group of glucagon receptor-like proteins, member of the class B family of seven-transmembrane G protein-coupled receptors; This group consists of uncharacterized proteins with similarity to members of the glucagon receptor family of G protein-coupled receptors, which include glucagon receptor (GCGR), and glucagon-like peptide-1 receptor (GLP1R), and GLP2R. The glucagon receptors are activated by the members of the glucagon (GCG) peptide family including GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from the large proglucagon precursor. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. Receptors in this group belong to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, 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. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 320651 [Multi-domain]  Cd Length: 280  Bit Score: 247.92  E-value: 4.80e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  94 LSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWIL-------YAEQDSNHCFIS- 165
Cdd:cd15985    2 VSFRMLYTVGYTLSLLTLVSALLILTSIRKLHCTRNYIHANLFASFILRAVSVIVKDTLLerrwgreIMRVADWGELLSh 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 166 --TVECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMN 243
Cdd:cd15985   82 kaAIGCRMAQVVMQYCILANHYWFFVEAVYLYKLLIGAVFSEKNYYLLYLYLGWGTPVLFVVPWMLAKYLKENKECWALN 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 244 DSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGgnESSIYLRLARSTLLLIPLFGIHYTVFAFSPEN----V 319
Cdd:cd15985  162 ENMAYWWIIRIPILLASLINLLIFMRILKVILSKLRANQKG--YADYKLRLAKATLTLIPLFGIHEVVFIFATDEqttgI 239
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 530384486 320 SKRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15985  240 LRYIKVFFTLFLNSFQGFLVAVLYCFANKEVKSELLKKWR 279
7tmB1_NPR_B7_insect-like cd15273
insect neuropeptide receptor subgroup B7 and related proteins, member of the class B family of ...
96-360 1.05e-78

insect neuropeptide receptor subgroup B7 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 invertebrates. 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: 320401 [Multi-domain]  Cd Length: 285  Bit Score: 244.59  E-value: 1.05e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  96 VKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFI----------- 164
Cdd:cd15273    4 IKGISQIGYIVSLITLIIAFAIFLSFKKLHCARNKLHMHLFASFILRAFMTLLKDSLFIDGLGLLADIVerngggnevia 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 165 ---STVECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWD 241
Cdd:cd15273   84 nigSNWVCKAITSLWQYFIIANYSWILMEGLYLHNLIFLALFSDENNIILYILLGWGLPLIFVVPWIVARILFENSLCWT 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 242 MNDSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMggNESSIYLRLARSTLLLIPLFGIHYTVFaFSPENVSK 321
Cdd:cd15273  164 TNSNLLNFLIIRIPIMISVLINFILFLNIVRVLLVKLRSSVN--EDSRRYKKWAKSTLVLVPLFGVHYTIF-LILSYLDD 240
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*
gi 530384486 322 RER------LVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15273  241 TNEaveliwLFCDQLFASFQGFFVALLYCFLNGEVRAEIQRKWRR 285
7tmB1_GLP1R cd15268
glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G ...
94-358 9.95e-74

glucagon-like peptide-1 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; Glucagon-like peptide-1 receptor (GLP1R) is a member of the glucagon receptor family of G protein-coupled receptors, which also includes glucagon receptor and GLP2R. GLP1R is activated by glucagon-like peptide 1 (GLP1), which is derived from the large proglucagon precursor. Activation of GLP1R stimulates glucose-dependent insulin secretion from pancreatic beta cells, whereas activation of GLP2R stimulates intestinal epithelial proliferation and increases villus height in the small intestine. GCGR regulates blood glucose levels by control of hepatic glycogenolysis and gluconeogenesis and by regulation of insulin secretion from the pancreatic beta-cells. Receptors in this group belong to the B1 (or secretin-like) subfamily of class B GPCRs, which includes receptors for polypeptide hormones of 27-141 amino-acid residues such as secretin, 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. However, depending on their cellular location, GCGR and GLP receptors can activate multiple G proteins, which can in turn stimulate different second messenger pathways.


Pssm-ID: 341342 [Multi-domain]  Cd Length: 279  Bit Score: 231.76  E-value: 9.95e-74
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  94 LSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWIL---YAEQDSNH------CFI 164
Cdd:cd15268    2 LFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALkwmYSTAAQQHqwdgllSYQ 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 165 STVECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMND 244
Cdd:cd15268   82 DSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVFSEQRIFRLYLSIGWGVPLLFVIPWGIVKYLYEDEGCWTRNS 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 245 STALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGgnESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRE- 323
Cdd:cd15268  162 NMNYWLIIRLPILFAIGVNFLIFIRVICIVVSKLKANLMC--KTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTl 239
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 530384486 324 ---RLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15268  240 rfvKLFTELSFTSFQGLMVAILYCFVNNEVQMEFRKSW 277
7tmB1_PTH3R cd15983
parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G ...
99-358 3.03e-72

parathyroid hormone 3 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone 3 receptor (PTH3R), one of the three subtypes of PTH receptor family, is found in chicken and fish, but it is absent in mammals. On the other hand, the PTH1R is found in all vertebrate species, whereas PTH2R is found in mammals and fish, but not in chicken or frog. PTH1R 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. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39), but not by PTHrP. PTH also strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs, suggesting that TIP-39 is a natural ligand for PTH2R. Conversely, PTH3R binds and responds to both PTH and PTHrP, but not the TIP-39. The PTH family 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: 320649 [Multi-domain]  Cd Length: 285  Bit Score: 228.27  E-value: 3.03e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  99 LYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHCFISTVE---------- 168
Cdd:cd15983    7 MYTIGYSISLAALLVAVCILCYFKRLHCTRNYIHIHLFASFICRAGSIFVKDAVLYSGTNEGEALDEKIEfglspgtrlq 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 ---CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNdS 245
Cdd:cd15983   87 wvgCKVTVTLFLYFLATNHYWILVEGLYLHSLIFMAFLSDKNYLWALTIIGWGLPAVFVSVWASVRVSLADTQCWDLS-A 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 246 TALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGG-NESSIYLRLARSTLLLIPLFGIHYTVFAFSP----ENVS 320
Cdd:cd15983  166 GNLKWIYQVPILAAILVNFFLFLNIVRVLASKLWETNTGKlDPRQQYRKLLKSTLVLMPLFGVHYVLFMAMPytdvTGLL 245
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 530384486 321 KRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15983  246 WQIQMHYEMLFNSSQGFFVAFIYCFCNGEVQAEIKKAW 283
7tmB1_PTH2R cd15982
parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G ...
99-358 4.86e-70

parathyroid hormone 2 receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; The parathyroid hormone 2 receptor (PTH2R), one of the three subtypes of PTH receptor family, is found in mammals and fish, but not in chicken or frog. PTH2R is potently activated by tuberoinfundibular peptide-39 (TIP-39) but not by PTH-related peptide (PTHrP), a paracrine factor that regulates endochondral bone development. PTH, an endocrine hormone that regulates calcium homoeostasis and bone maintenance, strongly activates human PTH2R, but only weakly activates rat and zebrafish PTH2Rs. These results suggest that TIP-39 is a natural ligand for PTH2R. Conversely, PTH1R is activated by PTH and PTHrP, but not by TIP-39. The PTH family 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: 320648 [Multi-domain]  Cd Length: 289  Bit Score: 222.50  E-value: 4.86e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  99 LYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAE-----------QDSNHCFIST- 166
Cdd:cd15982    7 MYTVGYSISFSSLAVAIFIIGYFRRLHCTRNYIHMHLFVSFMLRAASIFVKDKVVHTHigvkeldavlmNDFQNAVDAPp 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 167 ------VECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCW 240
Cdd:cd15982   87 vdksqyVGCKIAVVMFIYFLATNYYWILVEGLYLHSLIFVAFFSDTKYLWGFTLIGWGFPAVFVAAWAVVRATLADARCW 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 241 DMNdSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNES-SIYLRLARSTLLLIPLFGIHYTVFAFSP--- 316
Cdd:cd15982  167 ELS-AGDIKWIYQAPILAAIGLNFILFLNTVRVLATKIWETNAVGYDTrKQYRKLAKSTLVLVLVFGVHYIVFVCLPhtf 245
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 530384486 317 ENVSKRERLVFELGLGSFQGFVVAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15982  246 TGLGWEIRMHCELFFNSFQGFFVSIIYCYCNGEVQTEIKKTW 287
7tmB1_NPR_B4_insect-like cd15260
insect neuropeptide receptor subgroup B4 and related proteins, member of the class B family of ...
96-359 4.64e-68

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: 216.76  E-value: 4.64e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  96 VKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISvfikdWILYAEQDSNHCFI---STVECKAV 172
Cdd:cd15260    4 VNYVYIGGYSVSLIALIISLAIFFSFRSLRCTRITIHMNLFISFALNNLL-----WIVWYKLVVDNPEVlleNPIWCQAL 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYF-DDTG-CWdMNDSTAlWW 250
Cdd:cd15260   79 HVLLQYFMVCNYFWMFCEGLYLHTVLVVAFISEKSLMRWFIAIGWGVPLVITAIYAGVRASLpDDTErCW-MEESSY-QW 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 251 VIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDmGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERlVFELG 330
Cdd:cd15260  157 ILIVPVVLSLLINLIFLINIVRVLLTKLRATS-PNPAPAGLRKAVRATLILIPLLGLQFLLIPFRPEPGAPLET-IYQYV 234
                        250       260       270
                 ....*....|....*....|....*....|..
gi 530384486 331 ---LGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15260  235 salLTSLQGLCVAVLFCFCNGEVIAAIKRKWR 266
7tmB1_CRF-R cd15264
corticotropin-releasing factor receptors, member of the class B family of seven-transmembrane ...
93-358 2.22e-62

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: 201.88  E-value: 2.22e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIkdwiLYAEQDSNHCFISTVECKAV 172
Cdd:cd15264    1 YKVALIIYYLGFSISLVALAVALIIFLYFRSLRCLRNNIHCNLIVTFILRNVTWFI----MQNTLTEIHHQSNQWVCRLI 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCW-DMNDSTALWWV 251
Cdd:cd15264   77 VTVYNYFQVTNFFWMFVEGLYLHTMIVWAYSADKIRFWYYIVIGWCIPCPFVLAWAIVKLLYENEHCWlPKSENSYYDYI 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 252 IKGPVVGSIMVNFVLFIGIIVILVQKLQSPDmggNESSIYLRLA-RSTLLLIPLFGIHYTVFAFSPEN--VSKRERLVFE 328
Cdd:cd15264  157 YQGPILLVLLINFIFLFNIVWVLITKLRASN---TLETIQYRKAvKATLVLLPLLGITYMLFFINPGDdkTSRLVFIYFN 233
                        250       260       270
                 ....*....|....*....|....*....|
gi 530384486 329 LGLGSFQGFVVAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15264  234 TFLQSFQGLFVAVFYCFLNGEVRSAIRKKF 263
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
99-354 1.24e-54

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: 181.64  E-value: 1.24e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  99 LYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEqdsnhcfiSTVECKAVMVFFHY 178
Cdd:cd13952    7 ITYIGCSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLLTSSD--------RPVLCKALAILLHY 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 179 CVVSNYFWLFIEGLYLFTLLVETFF-PERRYFYWYTIIGWGTPTVCVTVWATLRL-------YFDDTGCWdMNDSTALWW 250
Cdd:cd13952   79 FLLASFFWMLVEAFDLYRTFVKVFGsSERRRFLKYSLYGWGLPLLIVIITAIVDFslygpspGYGGEYCW-LSNGNALLW 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 251 VIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMgGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELG 330
Cdd:cd13952  158 AFYGPVLLILLVNLVFFILTVRILLRKLRETPK-QSERKSDRKQLRAYLKLFPLMGLTWIFGILAPFVGGSLVFWYLFDI 236
                        250       260
                 ....*....|....*....|....
gi 530384486 331 LGSFQGFVVAVLYCFLNGEVQAEI 354
Cdd:cd13952  237 LNSLQGFFIFLIFCLKNKEVRRLL 260
7tmB1_calcitonin_R cd15274
calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled ...
92-365 2.57e-54

calcitonin receptor, member of the class B family of seven-transmembrane G protein-coupled receptors; This group includes G protein-coupled receptors for calcitonin (CT) and calcitonin gene-related peptides (CGRPs). Calcitonin, a 32-amino acid peptide hormone, is involved in calcium metabolism in many mammalian species and acts to reduce blood calcium levels and directly inhibits bone resorption by acting on osteoclast. Thus, CT acts as an antagonist to parathyroid hormone and is commonly used in the treatment of bone disorders. The CT receptor is predominantly found in osteoclasts, kidney, and brain, and is primarily coupled to stimulatory G(s) protein, which leads to activation of adenylate cyclase, thereby increasing cAMP production. CGRP, a member of the calcitonin family of peptides, is a potent vasodilator and may contribute to migraine. It is expressed in the peripheral and central nervous system and exists in two forms in humans (alpha-CGRP and beta-CGRP). CGRP meditates its physiological effects through calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 1 (RAMP1), a single transmembrane domain protein. Thus, the CRLR/RAMP1 complex serves as a functional CGRP receptor. On the other hand, the CRLR/RAMP2 and CRLR/RAMP3 complexes function as adrenomedullin-specific receptors. The CT and CGRP receptors 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), 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.


Pssm-ID: 341343 [Multi-domain]  Cd Length: 274  Bit Score: 181.13  E-value: 2.57e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  92 YYLSVkalytVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIkdWILYAEQDSNHCFISTVECKA 171
Cdd:cd15274    5 YYLAI-----VGHSLSIATLLISLGIFFFFRSLSCQRVTLHKNLFLSYILNSIIIII--HLVAVVPNGELVARNPVSCKI 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 172 VMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWdMNDSTALWWV 251
Cdd:cd15274   78 LHFIHQYMMGCNYFWMLCEGIYLHTLIVVAVFAEKQRLMWYYLLGWGFPLIPTTIHAITRAVYYNDNCW-LSSETHLLYI 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 252 IKGPVVGSIMVNFVLFIGIIVILVQKLQspDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELG- 330
Cdd:cd15274  157 IHGPIMAALVVNFFFLLNIVRVLVTKLR--ETHEAESHMYLKAVKATLILVPLLGIQFVLFPWRPSGKILGKIYDYVMHs 234
                        250       260       270
                 ....*....|....*....|....*....|....*
gi 530384486 331 LGSFQGFVVAVLYCFLNGEVQAEIKRKWRSWKVNR 365
Cdd:cd15274  235 LIHFQGFFVATIFCFCNGEVQATLKRQWNQYKIQF 269
7tmB1_DH_R cd15263
insect diuretic hormone receptors, member of the class B family of seven-transmembrane G ...
99-351 7.08e-51

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: 172.17  E-value: 7.08e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  99 LYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISvfikdWILYAE-QDSNHCFISTveCKAVMVFFH 177
Cdd:cd15263    7 IYFIGYSLSLVALSLALWIFLYFKDLRCLRNTIHTNLMFTYILADLT-----WILTLTlQVSIGEDQKS--CIILVVLLH 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 178 YCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRlYFDDTGCWDMNDSTALW-------- 249
Cdd:cd15263   80 YFHLTNFFWMFVEGLYLYMLVVETFSGENIKLRVYAFIGWGIPAVVIVIWAIVK-ALAPTAPNTALDPNGLLkhcpwmae 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 250 ----WVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGgnESSIYLRLARSTLLLIPLFGIHYTVFAFSPENvsKRERL 325
Cdd:cd15263  159 hivdWIFQGPAILVLAVNLVFLVRIMWVLITKLRSANTV--ETQQYRKAAKALLVLIPLLGITYILVIAGPTE--GIAAN 234
                        250       260
                 ....*....|....*....|....*....
gi 530384486 326 VFELG---LGSFQGFVVAVLYCFLNGEVQ 351
Cdd:cd15263  235 IFEYVravLLSTQGFTVALFYCFLNTEVR 263
7tmB1_CRF-R1 cd15445
corticotropin-releasing factor receptor 1, member of the class B family of seven-transmembrane ...
102-359 3.76e-46

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: 159.72  E-value: 3.76e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAE-QDSNhcfisTVECKAVMVFFHYCV 180
Cdd:cd15445   10 LGHCISLVALLVAFVLFLRLRSIRCLRNIIHWNLITAFILRNATWFVVQLTMSPEvHQSN-----VVWCRLVTAAYNYFH 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 181 VSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALW-WVIKGPVVGS 259
Cdd:cd15445   85 VTNFFWMFGEGCYLHTAIVLTYSTDKLRKWMFICIGWCIPFPIIVAWAIGKLYYDNEKCWFGKRAGVYTdYIYQGPMILV 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 260 IMVNFVLFIGIIVILVQKLQSPDMggNESSIYLRLARSTLLLIPLFGIHYTVFAFSP--ENVSKRERLVFELGLGSFQGF 337
Cdd:cd15445  165 LLINFIFLFNIVRILMTKLRASTT--SETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDEISRIVFIYFNSFLESFQGF 242
                        250       260
                 ....*....|....*....|..
gi 530384486 338 VVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15445  243 FVSVFYCFLNSEVRSAVRKRWH 264
7tmB1_CRF-R2 cd15446
corticotropin-releasing factor receptor 2, member of the class B family of seven-transmembrane ...
102-358 7.93e-44

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: 153.58  E-value: 7.93e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNHcfistVECKAVMVFFHYCVV 181
Cdd:cd15446   10 LGHCISVGALVVAFLLFLCLRSIRCLRNIIHWNLITTFILRNVMWFLLQMIDHNIHESNE-----VWCRCITTIYNYFVV 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMNDSTALW-WVIKGPVVGSI 260
Cdd:cd15446   85 TNFFWMFVEGCYLHTAIVMTYSTDKLRKWVFLFIGWCIPCPIIVAWAIGKLYYENEQCWFGKEPGKYIdYIYQGPVILVL 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 261 MVNFVLFIGIIVILVQKLQSPDMggNESSIYLRLARSTLLLIPLFGIHYTVFAFSP--ENVSKRERLVFELGLGSFQGFV 338
Cdd:cd15446  165 LINFVFLFNIVRILMTKLRASTT--SETIQYRKAVKATLVLLPLLGITYMLFFVNPgeDDISQIVFIYFNSFLQSFQGFF 242
                        250       260
                 ....*....|....*....|
gi 530384486 339 VAVLYCFLNGEVQAEIKRKW 358
Cdd:cd15446  243 VSVFYCFLNGEVRSAARKRW 262
7tmB1_PDFR cd15261
The pigment dispersing factor receptor, member of the class B seven-transmembrane G ...
96-360 3.85e-42

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: 149.44  E-value: 3.85e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  96 VKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAIS--VFIKDWILYAEQDSNHCFISTVE----- 168
Cdd:cd15261    4 TRTLEIVGLCLSLVSLIISLFIFSYFRTLRNHRTRIHKNLFLAILLQVIIrlVLYIDQAITRSRGSHTNAATTEGrtins 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 ----CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWA-TLRLYFDDTGCWDMN 243
Cdd:cd15261   84 tpilCEGFYVLLEYAKTVMFMWMFIEGLYLHNIIVVSVFSGKPNYLFYYILGWGIPIVHTSAWAiVTLIKMKVNRCWFGY 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 244 DSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKL---QSPDMGGNESSIylrlaRSTLLLIPLFGIHYTVFAFSPEnvs 320
Cdd:cd15261  164 YLTPYYWILEGPRLAVILINLFFLLNIIRVLVSKLresHSREIEQVRKAV-----KAAIVLLPLLGITNILQMIPPP--- 235
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|....*...
gi 530384486 321 kRERLVFELG--------LGSFQGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15261  236 -LTSVIVGFAvwsysthfLTSFQGFFVALIYCFLNGEVKNVLKKFWRR 282
7tmB1_NPR_B3_insect-like cd15262
insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of ...
100-359 3.30e-40

insect neuropeptide receptor subgroup B3 and related proteins belong to subfamily B1 of hormone receptors; member of the class B secretin-like seven-transmembrane G protein-coupled receptors; This subgroup includes a neuropeptide receptor found in Bombyx mori (silk worm) and its closely related proteins from arthropods. 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: 320390 [Multi-domain]  Cd Length: 270  Bit Score: 144.13  E-value: 3.30e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 100 YTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQ-----DSNHCFISTVECKAVMV 174
Cdd:cd15262    8 HVAALSVSVVTSLPAVFIFYSYKRLRITRVILHRNLLISIIIRNILVIISKVFVILDAltssgDDTVMNQNAVVCRLLSI 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 175 FFHYCVVSNYFWLFIEGLYLFTLLVETFF--PERRYFYwytIIGWGTPTVCVTVWATLRLYFDDTGCWdMNDSTALWWVI 252
Cdd:cd15262   88 FERAARNAVFACMFVEGFYLHRLIVAVFAekSSIRFLY---VIGAVLPLFPVIIWAIIRALHNDHSCW-VVDIEGVQWVL 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQSpdmgGNESSIYLRLARSTLLLIPLFGIHYTVFAFSP---ENVSKRERLVFEL 329
Cdd:cd15262  164 DTPRLFILLVNTVLLVDIIRVLVTKLRN----TEENSQTKSTTRATLFLVPLFGLHFVITAYRPstdDCDWEDIYYYANY 239
                        250       260       270
                 ....*....|....*....|....*....|
gi 530384486 330 GLGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15262  240 LIEGLQGFLVAILFCYINKEVHYLIKNTYR 269
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
97-352 2.99e-30

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: 117.04  E-value: 2.99e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  97 KALYTVGY---STSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWIlyaeqdsnhcFISTVECKAVM 173
Cdd:cd15933    2 RALSIISYigcGISIACLALTLIIFLVLRVLSSDRFQIHKNLCVALLLAQILLLAGEWA----------EGNKVACKVVA 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 174 VFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYtIIGWGTPTVCVTVwaTLRLYFDDTG----CWdMNDSTALW 249
Cdd:cd15933   72 ILLHFFFMAAFSWMLVEGLHLYLMIVKVFNYKSKMRYYY-FIGWGLPAIIVAI--SLAILFDDYGspnvCW-LSLDDGLI 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 250 WVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIYLR-LARSTLLLIPLFGIHYtVFAFSPENvskRERLVFE 328
Cdd:cd15933  148 WAFVGPVIFIITVNTVILILVVKITVSLSTNDAKKSQGTLAQIKsTAKASVVLLPILGLTW-LFGVLVVN---SQTIVFQ 223
                        250       260
                 ....*....|....*....|....*..
gi 530384486 329 ---LGLGSFQGFVVAVLYCFLNGEVQA 352
Cdd:cd15933  224 yifVILNSLQGLMIFLFHCVLNSEVRS 250
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
102-351 1.78e-29

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: 114.98  E-value: 1.78e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHC-TRNFIHMNLFVSFMLrAISVFIkdwilYAEQDSNHcfisTVECKAVMVFFHYCV 180
Cdd:cd15040   10 IGCGLSLLGLLLTIITYILFRKLRKrKPTKILLNLCLALLL-ANLLFL-----FGINSTDN----PVLCTAVAALLHYFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 181 VSNYFWLFIEGLYLFTLLVETF-FPERRYFYWYTIIGWGTPT--VCVTVWATLRLYFDDTG-CWdMNDSTALWWVIKGPV 256
Cdd:cd15040   80 LASFMWMLVEALLLYLRLVKVFgTYPRHFILKYALIGWGLPLiiVIITLAVDPDSYGNSSGyCW-LSNGNGLYYAFLGPV 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 257 VGSIMVNFVLFIGIIVILVQKLQspDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVskreRLVFEL---GLGS 333
Cdd:cd15040  159 LLIILVNLVIFVLVLRKLLRLSA--KRNKKKRKKTKAQLRAAVSLFFLLGLTWIFGILAIFGA----RVVFQYlfaIFNS 232
                        250
                 ....*....|....*...
gi 530384486 334 FQGFVVAVLYCFLNGEVQ 351
Cdd:cd15040  233 LQGFFIFIFHCLRNKEVR 250
7tmB2_latrophilin-like_invertebrate cd15440
invertebrate latrophilin-like receptors, member of the class B2 family of seven-transmembrane ...
101-356 8.29e-21

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: 91.17  E-value: 8.29e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 101 TVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAIsVFIkdwiLYAEQDSNHcfistVECKAVMVFFHYCV 180
Cdd:cd15440    9 YIGCIISIVCLLLAFITFTCFRNLQCDRNTIHKNLCLCLLIAEI-VFL----LGIDQTENR-----TLCGVIAGLLHYFF 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 181 VSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPT--VCVTVWATLRLYFDDTGCWdMNDSTALWWVIKGPVVG 258
Cdd:cd15440   79 LAAFSWMLLEGFQLYVMLVEVFEPEKSRIKWYYLFGYGLPAliVAVSAGVDPTGYGTEDHCW-LSTENGFIWSFVGPVIV 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 259 SIMVNFVlFIGIIVILVQKLQSPDMGGNESSI---YLRLARSTLLLIPLFGIHYTVFAFspeNVSKRERL---VFELgLG 332
Cdd:cd15440  158 VLLANLV-FLGMAIYVMCRHSSRSASKKDASKlknIRGWLKGSIVLVVLLGLTWTFGLL---FINQESIVmayIFTI-LN 232
                        250       260
                 ....*....|....*....|....
gi 530384486 333 SFQGFVVAVLYCFLNGEVQAEIKR 356
Cdd:cd15440  233 SLQGLFIFIFHCVLNEKVRKELRR 256
7tmB2_CELSR_Adhesion_IV cd15441
cadherin EGF LAG seven-pass G-type receptors, group IV adhesion GPCRs, member of the class B2 ...
102-359 1.64e-19

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: 87.31  E-value: 1.64e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSfMLRAISVFIkdwiLYAEQDSNhcfisTVECKAVMVFFHYCVV 181
Cdd:cd15441   10 IGIGISLVLLVIAFLVLSCLRGLQSNSNSIHKNLVAC-LLLAELLFL----LGINQTEN-----LFPCKLIAILLHYFYL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATLRL--YFDDTGCWDMNDSTALWWVIkGPVVGS 259
Cdd:cd15441   80 SAFSWLLVESLHLYRMLTEPRDINHGHMRFYYLLGYGIPAIIVGLSVGLRPdgYGNPDFCWLSVNETLIWSFA-GPIAFV 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 260 IMVNFVLFI-GIIVILVQKLQSPDMGGNESSIylrlaRSTLLLIPLFGIhytVFAFSPENVSKRERLVFEL--GLGSFQG 336
Cdd:cd15441  159 IVITLIIFIlALRASCTLKRHVLEKASVRTDL-----RSSFLLLPLLGA---TWVFGLLAVNEDSELLHYLfaGLNFLQG 230
                        250       260
                 ....*....|....*....|...
gi 530384486 337 FVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15441  231 LFIFLFYCIFNKKVRRELKNALL 253
7tmB2_Latrophilin_Adhesion_I cd15252
Latrophilins and similar receptors, group I adhesion GPCRs, member of class B2 family of ...
93-359 3.54e-19

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: 86.41  E-value: 3.54e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  93 YLSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLfvsfmlrAISVFIKDWILYAEQDSNHcfiSTVECKAV 172
Cdd:cd15252    1 YNILTRITQVGIIISLVCLAICIFTFWFFRGLQSDRTTIHKNL-------CISLFLAELVFLIGINTTT---NKIFCSVI 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 173 MVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWDMNDSTALWW 250
Cdd:cd15252   71 AGLLHYFFLAAFAWMFIEGIQLYLMLVEVFENEGSRHKNFYIFGYGSPAVIVGVSAALgyRYYGTTKVCWLSTENYFIWS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 251 VIkGPVVGSIMVNfVLFIGIIVILVQKLQS---PDMGGNESSiyLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVF 327
Cdd:cd15252  151 FI-GPATLIILLN-LIFLGVAIYKMFRHTAglkPEVSCLENI--RSWARGAIALLFLLGLTWIFGVLHINHASVVMAYLF 226
                        250       260       270
                 ....*....|....*....|....*....|..
gi 530384486 328 ELgLGSFQGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15252  227 TV-SNSLQGMFIFLFHCVLSRKVRKEYYKLFR 257
7tmB2_GPR133 cd15256
orphan adhesion receptor GPR133, member of the class B2 family of seven-transmembrane G ...
94-357 8.44e-19

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: 85.36  E-value: 8.44e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  94 LSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRN---FIHMNLFVSFMLRAISVFIkdwilyaeqdSNHCFISTVECK 170
Cdd:cd15256    2 VALSSITYVGCSLSIFCLAITLVTFAVLSSVSTIRNqryHIHANLSFAVLVAQILLLI----------SFRFEPGTLPCK 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 171 AVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTV--CVTVWATLRLYFDDTGCWDMNDSTAL 248
Cdd:cd15256   72 IMAILLHFFFLSAFAWMLVEGLHLYSMVIKVFGSEESKHFYYYGIGWGSPLLicIISLTSALDSYGESDNCWLSLENGAI 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 249 WWVIkGPVVGSIMVNFVLFIGIIVILVQ-KLQSPDMGGNESSIYLRlARSTLLLIPLFGIHYTVFAFSPENVSKRERLVF 327
Cdd:cd15256  152 WAFV-APALFVIVVNIGILIAVTRVISRiSADNYKVHGDANAFKLT-AKAVAVLLPILGSSWVFGVLAVNTHALVFQYMF 229
                        250       260       270
                 ....*....|....*....|....*....|
gi 530384486 328 ELgLGSFQGFVVAVLYCFLNGEVQAEIKRK 357
Cdd:cd15256  230 AI-FNSLQGFFIFLFHCLLNSEVRAAFKHK 258
7tmB2_Latrophilin cd15436
Latrophilins, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
102-359 2.96e-16

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: 77.91  E-value: 2.96e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFvsfmlraISVFIKDWILYAEQDSNHcfiSTVECKAVMVFFHYCVV 181
Cdd:cd15436   10 VGIVISLVCLLICIFTFCFFRGLQTDRNTIHKNLC-------INLFIAELLFLIGINRTQ---YTIACPIFAGLLHFFFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLFTLLVETFFPE---RRYFYwytIIGWGTPTVCVTVWATL--RLYFDDTGCWDMNDSTALWWVIkGPV 256
Cdd:cd15436   80 AAFCWLCLEGVQLYLLLVEVFESEysrRKYFY---LCGYSFPALVVAVSAAIdyRSYGTEKACWLRVDNYFIWSFI-GPV 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 257 VGSIMVNFVLfigIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFEL--GLGSF 334
Cdd:cd15436  156 TFVITLNLVF---LVITLHKMVSHSDLLKPDSSRLDNIKSWALGAIALLFLLGLTWSFGLMFINEESVVMAYLftIFNAF 232
                        250       260
                 ....*....|....*....|....*
gi 530384486 335 QGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd15436  233 QGVFIFIFHCALQKKVRKEYSKCLR 257
7tmB2_EMR cd15439
epidermal growth factor-like module-containing mucin-like hormone receptors, member of the ...
102-356 3.02e-16

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: 78.15  E-value: 3.02e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLfvsfmlrAISVFIKDWILYAEQDSNHcfiSTVECKAVMVFFHYCVV 181
Cdd:cd15439   10 VGLIISLLCLFLAILTFLLCRSIRNTSTSLHLQL-------SLCLFLADLLFLVGIDRTD---NKVLCSIIAGFLHYLFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLF----TLLVETFFPERRYFYWYT-IIGWGTPTVCVTVWATLR--LYFDDTGCWdMNDSTALWWVIKG 254
Cdd:cd15439   80 ACFAWMFLEAVHLFltvrNLKVVNYFSSHRFKKRFMyPVGYGLPAVIVAISAAVNpqGYGTPKHCW-LSMEKGFIWSFLG 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 255 PVVGSIMVNFVLFIGIIVILVQKLQSpdMGGNESSIylrlaRSTLLLI-----PLF--GIHYTVFAFSPENVSKRERLVF 327
Cdd:cd15439  159 PVCVIIVINLVLFCLTLWILREKLSS--LNAEVSTL-----KNTRLLTfkaiaQLFilGCTWILGLFQVGPVATVMAYLF 231
                        250       260
                 ....*....|....*....|....*....
gi 530384486 328 ELgLGSFQGFVVAVLYCFLNGEVQAEIKR 356
Cdd:cd15439  232 TI-TNSLQGVFIFLVHCLLNRQVREEYRR 259
7tmB2_CD97 cd15438
CD97 antigen, member of the class B2 family of seven-transmembrane G protein-coupled receptors; ...
102-356 9.38e-16

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: 76.73  E-value: 9.38e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLfvsfmlrAISVFIKDWI--LYAEQDSNHcfistVECKAVMVFFHYC 179
Cdd:cd15438   10 VGLSVSLFCLFLCILTFLFCRSIRGTRNTIHLHL-------CLSLFLAHLIflLGINNTNNQ-----VACAVVAGLLHYF 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 180 VVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWdMNDSTALWWVIKGPVV 257
Cdd:cd15438   78 FLAAFCWMSLEGVELYLMVVQVFNTQSLKKRYLLLIGYGVPLVIVAISAAVnsKGYGTQRHCW-LSLERGFLWSFLGPVC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 258 GSIMVNFVLFIGIIVILVQKLQS--PDMGGnessiyLRLARS-TLLLIPLFGIHYTVFAFSPENVSKRERL---VFELgL 331
Cdd:cd15438  157 LIILVNAIIFVITVWKLAEKFSSinPDMEK------LRKIRAlTITAIAQLCILGCTWIFGFFQFSDSTLVmsyLFTI-L 229
                        250       260
                 ....*....|....*....|....*
gi 530384486 332 GSFQGFVVAVLYCFLNGEVQAEIKR 356
Cdd:cd15438  230 NSLQGLFIFLLHCLLSKQVREEYSR 254
7tmB2_Latrophilin-1 cd16007
Latrophilin-1, member of the class B2 family of seven-transmembrane G protein-coupled ...
102-359 9.01e-15

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: 73.80  E-value: 9.01e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLfvsfmlrAISVFIKDWILYAEQDSNHcfiSTVECKAVMVFFHYCVV 181
Cdd:cd16007   10 VGIVISLVCLAICISTFCFLRGLQTDRNTIHKNL-------CINLFLAELLFLIGIDKTQ---YQIACPIFAGLLHFFFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWDMNDSTALWWVIkGPVVGS 259
Cdd:cd16007   80 AAFSWLCLEGVQLYLMLVEVFESEYSRKKYYYLCGYCFPALVVGISAAIdyRSYGTEKACWLRVDNYFIWSFI-GPVSFV 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 260 IMVNFVLfigIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFEL--GLGSFQGF 337
Cdd:cd16007  159 IVVNLVF---LMVTLHKMIRSSSVLKPDSSRLDNIKSWALGAITLLFLLGLTWAFGLLFINKESVVMAYLftTFNAFQGM 235
                        250       260
                 ....*....|....*....|..
gi 530384486 338 VVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd16007  236 FIFIFHCALQKKVHKEYSKCLR 257
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
99-347 1.61e-14

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.


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 73.23  E-value: 1.61e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  99 LYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSnhcFISTVECKAVMVFFHY 178
Cdd:cd14964    4 ILSLLTCLGLLGNLLVLLSLVRLRKRPRSTRLLLASLAACDLLASLVVLVLFFLLGLTEAS---SRPQALCYLIYLLWYG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 179 CVVSNYFWLFIEGLYLFTLL----VETFFPERRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTG------CWDMNDSTAL 248
Cdd:cd14964   81 ANLASIWTTLVLTYHRYFALcgplKYTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRYNtltgscYLICTTIYLT 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 249 WWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNESSIY-LRLARSTLLLIPLFGIHYTVFAF-------SPENVS 320
Cdd:cd14964  161 WGFLLVSFLLPLVAFLVIFSRIVLRLRRRVRAIRSAASLNTDKnLKATKSLLILVITFLLCWLPFSIvfilhalVAAGQG 240
                        250       260
                 ....*....|....*....|....*..
gi 530384486 321 KRERLVFELGLGSFQGFVVAVLYCFLN 347
Cdd:cd14964  241 LNLLSILANLLAVLASTLNPFIYCLGN 267
7tmB2_GPR144 cd15255
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
94-356 5.72e-14

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: 71.42  E-value: 5.72e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  94 LSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEqdsnhcfistVECKAVM 173
Cdd:cd15255    2 ATLRTLSFIGCGVSLCALIVTFILFLAVGVPKSERTTVHKNLIFALAAAEFLLMFSEWAKGNQ----------VACWAVT 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 174 VFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPT--VCVTVWATLRLYFDDTGCWdMNDSTALWWV 251
Cdd:cd15255   72 ALLHLFFLAAFSWMLVEGLLLWSKVVAVNMSEDRRMKFYYVTGWGLPVviVAVTLATSFNKYVADQHCW-LNVQTDIIWA 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 252 IKGPVVGSIMVN-FVLFIGIIVILVQKLQSPDMGGNESSIYLRL-------ARSTLLLIPLFGIhyTVFAFSPENVSKRE 323
Cdd:cd15255  151 FVGPVLFVLTVNtFVLFRVVMVTVSSARRRAKMLTPSSDLEKQIgiqiwatAKPVLVLLPVLGL--TWLCGVLVHLSDVW 228
                        250       260       270
                 ....*....|....*....|....*....|...
gi 530384486 324 RLVFeLGLGSFQGFVVAVLYCFLNGEVQAEIKR 356
Cdd:cd15255  229 AYVF-ITLNSFQGLYIFLVYAIYNSEVRNAIQR 260
7tmB2_Latrophilin-2 cd16006
Latrophilin-2, member of the class B2 family of seven-transmembrane G protein-coupled ...
102-359 2.01e-13

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: 69.94  E-value: 2.01e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLfvsfmlrAISVFIKDWILYAEQDSNHcfiSTVECKAVMVFFHYCVV 181
Cdd:cd16006   10 VGIVISLVCLAICIFTFCFFRGLQSDRNTIHKNL-------CINLFIAEFIFLIGIDKTE---YKIACPIFAGLLHFFFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWDMNDSTALWWVIkGPVVGS 259
Cdd:cd16006   80 AAFAWMCLEGVQLYLMLVEVFESEYSRKKYYYVAGYLFPATVVGVSAAIdyKSYGTEKACWLRVDNYFIWSFI-GPVTFI 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 260 IMVNFVLFIGIIVILVQ-----KLQSPDMGGNESSIYlrlarSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELgLGSF 334
Cdd:cd16006  159 ILLNLIFLVITLCKMVKhsntlKPDSSRLENIKSWVL-----GAFALLCLLGLTWSFGLLFINEETIVMAYLFTI-FNAF 232
                        250       260
                 ....*....|....*....|....*
gi 530384486 335 QGFVVAVLYCFLNGEVQAEIKRKWR 359
Cdd:cd16006  233 QGMFIFIFHCALQKKVRKEYSKCFR 257
7tmB2_Latrophilin-3 cd16005
Latrophilin-3, member of the class B2 family of seven-transmembrane G protein-coupled ...
102-360 2.66e-13

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: 69.59  E-value: 2.66e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLfvsfmlrAISVFIKDWILYAEQDSNHcfiSTVECKAVMVFFHYCVV 181
Cdd:cd16005   10 VGILLSLVCLLICIFTFCFFRGLQSDRNTIHKNL-------CISLFVAELLFLIGINRTD---QPIACAVFAALLHFFFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLFTLLVETFFPE---RRYFYwytIIGWGTPTVCVTVWATL--RLYFDDTGCWDMNDSTALWWVIkGPV 256
Cdd:cd16005   80 AAFTWMFLEGVQLYIMLVEVFESEhsrRKYFY---LVGYGMPALIVAVSAAVdyRSYGTDKVCWLRLDTYFIWSFI-GPA 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 257 VGSIMVNfVLFIGIivILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELG--LGSF 334
Cdd:cd16005  156 TLIIMLN-VIFLGI--ALYKMFHHTAILKPESGCLDNIKSWVIGAIALLCLLGLTWAFGLMYINESTVIMAYLFtiFNSL 232
                        250       260
                 ....*....|....*....|....*.
gi 530384486 335 QGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd16005  233 QGMFIFIFHCVLQKKVRKEYGKCLRT 258
7tmB2_CELSR3 cd15993
Cadherin EGF LAG seven-pass G-type receptor 3, member of the class B2 family of ...
105-355 3.15e-13

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: 69.10  E-value: 3.15e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 105 STSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISvfikdWILYAEQDSNHCFistveCKAVMVFFHYCVVSNY 184
Cdd:cd15993   13 SASLAALVLTFSVLTCLRGLKSNTRGIHSNIAAALFLSELL-----FLLGINRTENQFL-----CTVVAILLHYFFLSTF 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 185 FWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWdMNDSTALWWVIKGPVVGSIMV 262
Cdd:cd15993   83 AWLFVQGLHIYRMQTEARNVNFGAMRFYYAIGWGVPAIITGLAVGLdpEGYGNPDFCW-ISIHDKLVWSFAGPIVVVIVM 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 263 NFVLFIGIIVILVQKLQ-----SPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSpenvskrerlVFELGLGSFQGF 337
Cdd:cd15993  162 NGVMFLLVARMSCSPGQketkkTSVLMTLRSSFLLLLLISATWLFGLLAVNNSVLAFH----------YLHAILCCLQGL 231
                        250
                 ....*....|....*...
gi 530384486 338 VVAVLYCFLNGEVQAEIK 355
Cdd:cd15993  232 AVLLLFCVLNEEVQEAWK 249
7tmB2_GPR126-like_Adhesion_VIII cd15258
orphan GPR126 and related proteins, group VIII adhesion GPCRs, member of the class B2 family ...
102-356 1.29e-12

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


Pssm-ID: 320386 [Multi-domain]  Cd Length: 267  Bit Score: 67.44  E-value: 1.29e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLhcTRNF---IHMNLFVSFMLRAISVFIKDWILYAEQDSnhcfistvECKAVMVFFHY 178
Cdd:cd15258   10 VGCGISAIFLAITILTYIAFRKL--RRDYpskIHMNLCAALLLLNLAFLLSSWIASFGSDG--------LCIAVAVALHY 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 179 CVVSNYFWLFIEGLYLFTLLVETFFPE-RRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTGCWDMND---STALWWvIKG 254
Cdd:cd15258   80 FLLACLTWMGLEAFHLYLLLVKVFNTYiRRYILKLCLVGWGLPALLVTLVLSVRSDNYGPITIPNGEgfqNDSFCW-IRD 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 255 PVVGSIMV----------NFVLFigiIVILVQKLQ-SPDMGGNESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRE 323
Cdd:cd15258  159 PVVFYITVvgyfgltflfNMVML---ATVLVQICRlREKAQATPRKRALHDLLTLLGLTFLLGLTWGLAFFAWGPFNLPF 235
                        250       260       270
                 ....*....|....*....|....*....|...
gi 530384486 324 RLVFELgLGSFQGFVVAVLYCFLNGEVQAEIKR 356
Cdd:cd15258  236 LYLFAI-FNSLQGFFIFIWYCSMKENVRKQWRA 267
7tmB2_EMR_Adhesion_II cd15931
EGF-like module receptors, group II adhesion GPCRs, member of class B2 family of ...
102-356 5.83e-12

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


Pssm-ID: 320597 [Multi-domain]  Cd Length: 262  Bit Score: 65.61  E-value: 5.83e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRaisvfiKDWILYAEQDSNhcfiSTVECKAVMVFFHYCVV 181
Cdd:cd15931   10 VGVIVSLFCLGLAIFTFLLCRWIPKINTTAHLHLCLCLSMS------HTLFLAGIEYVE----NELACTVMAGLLHYLFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLFTLLVETFfpERRYFY-------WYTIIGWGTPTVCVTVWATL--RLYFDDTGCWdMNDSTALWWVI 252
Cdd:cd15931   80 ASFVWMLLEALQLHLLVRRLT--KVQVIQrdglprpLLCLIGYGVPFLIVGVSALVysDGYGEAKMCW-LSQERGFNWSF 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 253 KGPVVGSIMVNFVLFIGIIVILVQKLQS--PDMGGNESSIYLRLARSTLLLIplFGIHYTVFAFSPENVSKRERLVFELg 330
Cdd:cd15931  157 LGPVIAIIGINWILFCATLWCLRQTLSNmnSDISQLKDTRLLTFKAVAQLFI--LGCTWVLGLFQTNPVALVFQYLFTI- 233
                        250       260
                 ....*....|....*....|....*.
gi 530384486 331 LGSFQGFVVAVLYCFLNGEVQAEIKR 356
Cdd:cd15931  234 LNSLQGAFLFLVHCLLNKEVREEYIK 259
7tmB2_CELSR1 cd15991
Cadherin EGF LAG seven-pass G-type receptor 1, member of the class B2 family of ...
94-355 7.66e-12

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


Pssm-ID: 320657 [Multi-domain]  Cd Length: 254  Bit Score: 64.87  E-value: 7.66e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  94 LSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLraiSVFIkdwILYAEQDSNHCFISTVeckaVM 173
Cdd:cd15991    2 LPLKIITYTTVSLSLVALLITFILLVLIRTLRSNLHSIHKNLVAALFF---SELI---FLIGINQTENPFVCTV----VA 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 174 VFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWdMNDSTALWWV 251
Cdd:cd15991   72 ILLHYFYMSTFAWMFVEGLHIYRMLTEVRNINTGHMRFYYVVGWGIPAIITGLAVGLdpQGYGNPDFCW-LSVQDTLIWS 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 252 IKGPVVGSIMVNFVLFIGIIVILVQKLQSPDmggnESSIYLRLARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELgL 331
Cdd:cd15991  151 FAGPIGIVVIINTVIFVLAAKASCGRRQRYF----EKSGVISMLRTAFLLLLLISATWLLGLMAVNSDTLSFHYLFAI-F 225
                        250       260
                 ....*....|....*....|....
gi 530384486 332 GSFQGFVVAVLYCFLNGEVQAEIK 355
Cdd:cd15991  226 SCLQGIFIFFFHCIFNKEVRKHLK 249
7tmB2_GPR116-like_Adhesion_VI cd15932
orphan GPR116 and related proteins, group IV adhesion GPCRs, member of the class B2 family of ...
102-355 8.50e-11

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: 61.94  E-value: 8.50e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKlHCTRNFIHMNLFVSFMLRAISVFIKD-WILYAEQDSNHCFISTVeCKAVMVFFHYCV 180
Cdd:cd15932   10 VGLGISILSLVLCLIIEALVWK-SVTKNKTSYMRHVCLVNIALSLLIADiWFIIGAAISTPPNPSPA-CTAATFFIHFFY 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 181 VSNYFWLFIEGLYLF--TLLVETFFPERRYFYWYTIIGWGTPTV--CVTVWATL--RLYFDDTGCW-DMNDSTALWWVIk 253
Cdd:cd15932   88 LALFFWMLTLGLLLFyrLVLVFHDMSKSTMMAIAFSLGYGCPLIiaIITVAATApqGGYTRKGVCWlNWDKTKALLAFV- 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 254 GPVVGSIMVNFVlfigIIVILVQKLQSPDMG----GNESSIYLRLARSTLLLIPLFGIHY-----TVFafspENVSKRER 324
Cdd:cd15932  167 IPALAIVVVNFI----ILIVVIFKLLRPSVGerpsKDEKNALVQIGKSVAILTPLLGLTWgfglgTMI----DPKSLAFH 238
                        250       260       270
                 ....*....|....*....|....*....|.
gi 530384486 325 LVFELgLGSFQGFVVAVLYCFLNGEVQAEIK 355
Cdd:cd15932  239 IIFAI-LNSFQGFFILVFGTLLDSKVREALL 268
7tmB2_ETL cd15437
Epidermal Growth Factor, latrophilin and seven transmembrane domain-containing protein 1; ...
102-356 1.87e-10

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: 61.05  E-value: 1.87e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKdwilyAEQDSNHCFistveCKAVMVFFHYCVV 181
Cdd:cd15437   10 LGIIISLICLSMCIFTFWFFSEIQSTRTTIHKNLCCSLFLAELIFLIG-----INMNANKLF-----CSIIAGLLHYFFL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 182 SNYFWLFIEGLYLFTLLVETFFPERRYFYWYTIIGWGTPTVCVTVWATL--RLYFDDTGCWDMNDSTALWWVIkGPVVGS 259
Cdd:cd15437   80 AAFAWMCIEGIHLYLIVVGVIYNKGFLHKNFYIFGYGSPAVVVGISAALgyKYYGTTKVCWLSTENNFIWSFI-GPACLI 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 260 IMVNFVLFigiIVILVQKLQSPDMGGNESSIYLRL---ARSTLLLIPLFGIHYTVFAFSPENVSKRERLVFELGlGSFQG 336
Cdd:cd15437  159 ILVNLLAF---GVIIYKVFRHTAMLKPEVSCYENIrscARGALALLFLLGATWIFGVLHVVYGSVVTAYLFTIS-NAFQG 234
                        250       260
                 ....*....|....*....|
gi 530384486 337 FVVAVLYCFLNGEVQAEIKR 356
Cdd:cd15437  235 MFIFIFLCVLSRKIQEEYYR 254
7tmB3_Methuselah-like cd15039
Methuselah-like subfamily B3, member of the class B family of seven-transmembrane G ...
99-268 2.44e-09

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: 57.62  E-value: 2.44e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  99 LYTVGYSTSLVTLTTAMVILCRFRKLHCT--RNFIHM--NLFVSFMLRAISVFIKDWILYAeqdsnhcfistveCKAVMV 174
Cdd:cd15039    7 LTLIGLIISLVFLLLTLAVYALLPELRNLhgKCLMCLvlSLFVAYLLLLIGQLLSSGDSTL-------------CVALGI 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 175 FFHYCVVSNYFWLFIEGLYLF-----TLLVETFFPERRYFYWYTIIGWGTPTVCVTVWAT---------LRLYFDDTGCW 240
Cdd:cd15039   74 LLHFFFLAAFFWLNVMSFDIWrtfrgKRSSSSRSKERKRFLRYSLYAWGVPLLLVAVTIIvdfspntdsLRPGYGEGSCW 153
                        170       180
                 ....*....|....*....|....*...
gi 530384486 241 dMNDSTALWWVIKGPVVGSIMVNFVLFI 268
Cdd:cd15039  154 -ISNPWALLLYFYGPVALLLLFNIILFI 180
7tmB2_GPR64 cd15444
orphan adhesion receptor GPR64 and related proteins, member of subfamily B2 of the class B ...
169-361 1.28e-08

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


Pssm-ID: 320560 [Multi-domain]  Cd Length: 271  Bit Score: 55.60  E-value: 1.28e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPE-RRYFYWYTIIGWGTPTVCVTVWATLR--LY-FDDTGCWDMND 244
Cdd:cd15444   71 CISVAVFLHYFLLVSFTWMGLEAFHMYLALVKVFNTYiRKYILKFCIVGWGVPAVVVAIVLAVSkdNYgLGSYGKSPNGS 150
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 245 STALWWVIKG-----PVVGSIMVNFVLFIGI-IVILVQ--KLQSPDMGGNESSIYLRLARSTLLLIPLFGIH--YTVFAF 314
Cdd:cd15444  151 TDDFCWINNNivfyiTVVGYFCVIFLLNISMfIVVLVQlcRIKKQKQLGAQRKTSLQDLRSVAGITFLLGITwgFAFFAW 230
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 530384486 315 SPENVSKRERLVFelgLGSFQGFVVAVLYCFlngeVQAEIKRKWRSW 361
Cdd:cd15444  231 GPVNLAFMYLFAI---FNTLQGFFIFIFYCV----AKENVRKQWRRY 270
7tmB2_BAI_Adhesion_VII cd15251
brain-specific angiogenesis inhibitors, group VII adhesion GPCRs, member of the class B2 ...
102-355 2.30e-08

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: 54.57  E-value: 2.30e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRF-RKLHCTRNFIHMNLFVSFMLRAISVFIKdwilyaeQDSNHcfiSTVECKAVMVFFHYCV 180
Cdd:cd15251   10 VGCGVSCLALLTLLAIYAAFwRYIRSERSIILINFCLSIISSNILILVG-------QTQTL---NKGVCTMTAAFLHFFF 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 181 VSNYFWLFIEGLYLFtLLVETFFPERRYFYWYTIIGWGTPTVCVTV---WATLRLYFDDTGCWdMNDSTALWWVIKGPVV 257
Cdd:cd15251   80 LSSFCWVLTEAWQSY-MAVTGRMRTRLIRKRFLCLGWGLPALVVAVsvgFTRTKGYGTSSYCW-LSLEGGLLYAFVGPAA 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 258 GSIMVNFVlfIGIIVIlvQKLQSPDMGGNESSIYLRlarSTLLLIPLFGIHYTVFAFSpenVSKRERLVFELGLGSF--- 334
Cdd:cd15251  158 AVVLVNMV--IGILVF--NKLVSRDGISDNAMASLW---SSCVVLPLLALTWMSAVLA---MTDRRSVLFQILFAVFdsl 227
                        250       260
                 ....*....|....*....|.
gi 530384486 335 QGFVVAVLYCFLNGEVQAEIK 355
Cdd:cd15251  228 QGFVIVMVHCILRREVQDAVK 248
7tmB2_GPR113 cd15253
orphan adhesion receptor GPR113, member of the class B2 family of seven-transmembrane G ...
169-357 3.90e-08

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: 54.00  E-value: 3.90e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETF--FPERRYFYWYTIIGWGTP----TVCVTVWATLRLYFDDTGCWDM 242
Cdd:cd15253   75 CLAAAFLCHFFYLATFFWMLVQALMLFHQLLFVFhqLAKRSVLPLMVTLGYLCPlliaAATVAYYYPKRQYLHEGACWLN 154
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 243 NDSTALwWVIKGPVVGSIMVNFVlfigIIVILVQKLQSPDMG----GNESSIYLRLARSTLLLIPLFGIHYTV-FAFSPE 317
Cdd:cd15253  155 GESGAI-YAFSIPVLAIVLVNLL----VLFVVLMKLMRPSVSegppPEERKALLSIFKALLVLTPVFGLTWGLgVATLTG 229
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 530384486 318 NVSKRERLVFElGLGSFQGFVVAVLYCFLNGEVQAEIKRK 357
Cdd:cd15253  230 ESSQVSHYGFA-ILNAFQGVFILLFGCLMDKKVREALLKR 268
7tmB2_GPR128 cd15257
orphan adhesion receptor GPR128, member of the class B2 family of seven-transmembrane G ...
169-354 2.03e-07

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


Pssm-ID: 320385 [Multi-domain]  Cd Length: 303  Bit Score: 52.18  E-value: 2.03e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPERRYFYWY-TIIGWGTPTVCV--TVWATLRL----------YFD 235
Cdd:cd15257   93 CTAVAALLHYFLLVTFMWNAVYSAQLYLLLIRMMKPLPEMFILQaSAIGWGIPAVVVaiTLGATYRFptslpvftrtYRQ 172
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 236 DTGCW----DMNDS--TALWWVIKGPVVGSIMVNFVLFIGIIVILVQKlQSPDMGGNESSiYLRLARSTLLLIPLFGIHY 309
Cdd:cd15257  173 EEFCWlaalDKNFDikKPLLWGFLLPVGLILITNVILFIMTSQKVLKK-NNKKLTTKKRS-YMKKIYITVSVAVVFGITW 250
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 530384486 310 tVFAFSPENVSKRERLVFEL---GLGSFQGFVVAVLYCFLNGEVQAEI 354
Cdd:cd15257  251 -ILGYLMLVNNDLSKLVFSYifcITNTTQGVQIFILYTWRTPEFRKLV 297
7tmB2_GPR97 cd15442
orphan adhesion receptor GPR97, member of the class B2 family of seven-transmembrane G ...
95-346 2.50e-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: 51.72  E-value: 2.50e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  95 SVKALYTVGYSTSLV--TLTTAMVILCRF-RKLHCTRNF--IHMNLFVSFMLRAISVFIKDWILYAEQDSnhcfistvEC 169
Cdd:cd15442    3 TLVTISSAGCGVSMVflIFTIILYFFLRFtYQKFKSEDApkIHVNLSSSLLLLNLAFLLNSGVSSRAHPG--------LC 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 170 KAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPE-RRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTgCWDMNDSTA- 247
Cdd:cd15442   75 KALGGVTHYFLLCCFTWMAIEAFHLYLLAIKVFNTYiHHYFAKLCLVGWGFPALVVTITGSINSYGAYT-IMDMANRTTl 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 248 -LWWVIKGPVV-------GSIMVNFVLFIGIIVILVQK---LQSPDMGGNESSIYlRLARSTLLLIPLFGIHYTVFAFSP 316
Cdd:cd15442  154 hLCWINSKHLTvhyitvcGYFGLTFLFNTVVLGLVAWKifhLQSATAGKEKCQAW-KGGLTVLGLSCLLGVTWGLAFFTY 232
                        250       260       270
                 ....*....|....*....|....*....|
gi 530384486 317 ENVSKRERLVFELgLGSFQGFVVAVLYCFL 346
Cdd:cd15442  233 GSMSVPTVYIFAL-LNSLQGLFIFIWFVIL 261
7tmB2_GPR112 cd15997
Probable G protein-coupled receptor 112, member of the class B2 family of seven-transmembrane ...
169-359 2.83e-07

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: 51.58  E-value: 2.83e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPE-RRYFYWYTIIGWGTPTVCVTVWATLRLYFDDTG--------- 238
Cdd:cd15997   70 CITVAAFLHYFLLASFTWMGLEAVHMYFALVKVFNIYiPNYILKFCIAGWGIPAVVVALVLAINKDFYGNElssdslhps 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 239 ---CWdMNDSTALWWVIKGPVVGSIMVNFVLFIgIIVILVQKLQSPDMGGNESSIYLRLARSTLLLIPLFGIHYTV--FA 313
Cdd:cd15997  150 tpfCW-IQDDVVFYISVVAYFCLIFLCNISMFI-TVLIQIRSMKAKKPSRNWKQGFLHDLKSVASLTFLLGLTWGFafFA 227
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 530384486 314 FSPENVSKreRLVFELgLGSFQGFVVAVLYCFLNGEVQaeikRKWR 359
Cdd:cd15997  228 WGPVRIFF--LYLFSI-CNTLQGFFIFVFHCLMKENVR----KQWR 266
7tmB2_GPR114 cd15443
orphan adhesion receptor GPR114, member of the class B2 family of seven-transmembrane G ...
101-224 4.08e-07

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: 50.91  E-value: 4.08e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 101 TVGYSTSLVTLTTAMVILCRFRKL-HCTRNFIHMNLFVSFMLRAISVFIKDWILYaeqdsnhcFISTVECKAVMVFFHYC 179
Cdd:cd15443    9 IVGCSISAAASLLTILLHFFSRKQpKDSTTRIHMNLLGSLFLLNGSFLLSPPLAT--------SQSTWLCRAAAALLHYS 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 530384486 180 VVSNYFWLFIEGLYLFTLLVETF-FPERRYFYWYTIIGWGTPTVCV 224
Cdd:cd15443   81 LLCCLTWMAIEGFHLYLLLVKVYnIYIRRYVLKLCVLGWGLPALIV 126
HRM pfam02793
Hormone receptor domain; This extracellular domain contains four conserved cysteines that ...
46-80 4.32e-07

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


Pssm-ID: 397086  Cd Length: 64  Bit Score: 46.59  E-value: 4.32e-07
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 530384486   46 GFNDSSPDmGVVSRNCTEDG-WSEPFPHYFDACGFD 80
Cdd:pfam02793  30 YFSGFDPR-GNASRNCTEDGtWSEHPPSNYSNCTSN 64
7tmB2_GPR126 cd15996
orphan adhesion receptor GPR126, member of the class B2 family of seven-transmembrane G ...
131-356 5.93e-07

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: 50.66  E-value: 5.93e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 131 IHMNLFVSFMLRAISVFIKDWILYAEQDSnhcfistvECKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPE-RRYF 209
Cdd:cd15996   40 ILMNLSTALLFLNLVFLLDGWIASFEIDE--------LCITVAVLLHFFLLATFTWMGLEAIHMYIALVKVFNTYiRRYI 111
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 210 YWYTIIGWGTPTVCVTVWATLR----LYFDDTGCWDMNDSTALWWvIKGPVV------GSIMVNFVLFIGI-IVILVQKL 278
Cdd:cd15996  112 LKFCIIGWGLPALIVSIVLASTndnyGYGYYGKDKDGQGGDEFCW-IKNPVVfyvtcaAYFGIMFLMNVAMfIVVMVQIC 190
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 279 QSPDMGGNES--SIYLRLARSTLLLIPLFGIH--YTVFAFSPENVSKreRLVFELgLGSFQGFVVAVLYCFLNGEVQAEI 354
Cdd:cd15996  191 GRNGKRSNRTlrEEILRNLRSVVSLTFLLGMTwgFAFFAWGPVNLAF--MYLFTI-FNSLQGLFIFVFHCALKENVQKQW 267

                 ..
gi 530384486 355 KR 356
Cdd:cd15996  268 RR 269
HormR smart00008
Domain present in hormone receptors;
46-86 2.78e-06

Domain present in hormone receptors;


Pssm-ID: 214468  Cd Length: 70  Bit Score: 44.81  E-value: 2.78e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 530384486    46 GFNDSSPDmGVVSRNCTEDG-WSEPFPhYFDACGFDEYESET 86
Cdd:smart00008  31 YFSGFSYK-TGASRNCTENGgWSPPFP-NYSNCTSNDYEELK 70
7tmB2_GPR116_Ig-Hepta cd15254
The immunoglobulin-repeat-containing receptor Ig-hepta/GPR116, member of the class B2 family ...
102-351 3.68e-06

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: 48.26  E-value: 3.68e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRFRKlHCTRNFIHMNLFVSFMLRAISVFIKD-W--ILYAEQDSNHCFISTVeCKAVMVFFHY 178
Cdd:cd15254   10 IGLSISILSLAICIVIESLVWK-SVTKNRTSYMRHVCILNIAVSLLIADiWfiVVAAIQDQNYAVNGNV-CVAATFFIHF 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 179 CVVSNYFWLFIEGLYLFTLLVETFFPERRyfywyTI-------IGWGTPTV--CVTVWATL--RLYFDDTGCW-DMNDST 246
Cdd:cd15254   88 FYLCVFFWMLALGLMLFYRLVFILHDTSK-----TIqkavafcLGYGCPLIisVITIAVTLprDSYTRKKVCWlNWEDSK 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 247 ALWWVIkgpVVGSIMVNFVLFIGIIVILvqKLQSPDMG----GNESSIYLRLARSTLLLIPLFGIhytVFAFSPENVSKR 322
Cdd:cd15254  163 ALLAFV---IPALIIVAVNSIITVVVIV--KILRPSIGekpsKQERSSLFQIIKSIGVLTPLLGL---TWGFGLATVIKG 234
                        250       260       270
                 ....*....|....*....|....*....|..
gi 530384486 323 ERLVFELG---LGSFQGFVVAVLYCFLNGEVQ 351
Cdd:cd15254  235 SSIVFHILftlLNAFQGLFILVFGTLWDKKVQ 266
7tmB2_GPR124-like_Adhesion_III cd15259
orphan GPR124 and related proteins, group III adhesion GPCRs, member of class B2 family of ...
169-362 6.25e-06

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: 47.37  E-value: 6.25e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFP---------ERRYFYWYTIIGWGTPT-VC-VTVWATLRLYFDDT 237
Cdd:cd15259   70 CQAVGILLHYSTLCTLLWVGVTARNMYKQVTKTAKPpqdedqpprPPKPMLRFYLIGWGIPLiICgITAAVNLDNYSTYD 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 238 GCWDMNDSTALWWVikGPVVGSIMVNFVLFIGIIVILVQKLQSPdmggnesSIYLRLARSTLLLIPLFgihytvFAFSPE 317
Cdd:cd15259  150 YCWLAWDPSLGAFY--GPAALIVLVNCIYFLRIYCQLKGAPVSF-------QSQLRGAVITLFLYVAM------WACGAL 214
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 530384486 318 NVSKRE--RLVFELGLG---SFQGFVVAVLYCFLNGEVqaeikrkWRSWK 362
Cdd:cd15259  215 AVSQRYflDLVFSCLYGatcSSLGLFVLIHHCLSREDV-------RQSWR 257
7tmB2_GPR111_115 cd15994
orphan adhesion receptors GPR111 and GPR115, member of the class B2 family of ...
169-350 2.16e-05

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: 45.60  E-value: 2.16e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 169 CKAVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFF--PERRYFYWYTIIGWGTPTV--CVTVWATL--RLYFDDTGCWDM 242
Cdd:cd15994   76 CVAATFFLHFFYLSLFFWMLTKALLILYGILLVFFkiTKSVFIATAFSIGYGCPLViaVLTVAITEpkKGYLRPEACWLN 155
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 243 NDSTALWWVIKGPVVGSIMVNFVlfigIIVILVQKLQSPDMGGN---ESSIYLRLARSTLLLIPLFGIHYTV-FAFSPEN 318
Cdd:cd15994  156 WDETKALLAFIIPALSIVVVNLI----VVGVVVVKTQRSSIGESckqDVSNIIRISKNVAILTPLLGLTWGFgLATIIDS 231
                        170       180       190
                 ....*....|....*....|....*....|..
gi 530384486 319 VSKRERLVFELgLGSFQGFVVAVLYCFLNGEV 350
Cdd:cd15994  232 RSLPFHIIFAL-LNAFQGFFILLFGTILDRKI 262
7tmB2_BAI2 cd15988
brain-specific angiogenesis inhibitor 2, a group VII adhesion GPCR, member of the class B2 ...
102-355 5.68e-05

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: 44.56  E-value: 5.68e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 102 VGYSTSLVTLTTAMVILCRF-RKLHCTRNFIHMNLFVSFMLRAISVFIkdwilyaeqdSNHCFISTVECKAVMVFFHYCV 180
Cdd:cd15988   10 IGCAVSCMALLILLAIYAAFwRFIRSERSIILLNFCLSILASNILILV----------GQSQTLSKGVCTMTAAFLHFFF 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 181 VSNYFWLFIEGLYLFTLLV---ETFFPERRYFywytIIGWGTPTVCVTV---WATLRLYFDDTGCWdMNDSTALWWVIKG 254
Cdd:cd15988   80 LSSFCWVLTEAWQSYLAVIgrmRTRLVRKRFL----CLGWGLPALVVAVsvgFTRTKGYGTASYCW-LSLEGGLLYAFVG 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 255 PVVGSIMVNfvLFIGIIVIlvQKLQSPD---------MGGNESSIYLRL-------------------ARSTL------- 299
Cdd:cd15988  155 PAAVIVLVN--MLIGIIVF--NKLMSRDgisdkskkqRAGSEAEPCSSLllkcskcgvvssaamssatASSAMaslwssc 230
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 530384486 300 LLIPLFGIHYTVFAFSpenVSKRERLVFELGLGSF---QGFVVAVLYCFLNGEVQAEIK 355
Cdd:cd15988  231 VVLPLLALTWMSAVLA---MTDRRSILFQVLFAVFnsvQGFVIITVHCFLRREVQDVVK 286
7tmB2_GPR56 cd15995
orphan adhesion receptor GPR56, member of the class B2 family of seven-transmembrane G ...
91-226 7.10e-05

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


Pssm-ID: 320661  Cd Length: 269  Bit Score: 44.05  E-value: 7.10e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  91 YYYLSVKAlYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKDWILYAEQDSNhcfistveCK 170
Cdd:cd15995    1 KHYLTILT-YVGCIISALASVFTIAFYLCSRRKPRDYTIYVHMNLLLAIFLLDTSFLISEPLALTGSEAA--------CR 71
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 530384486 171 AVMVFFHYCVVSNYFWLFIEGLYLFTLLVETFFPE-RRYFYWYTIIGWGTPTVCVTV 226
Cdd:cd15995   72 AGGMFLHFSLLACLTWMGIEGYNLYRLVVEVFNTYvPHFLLKLCAVGWGLPIFLVTL 128
7tmB2_CELSR2 cd15992
Cadherin EGF LAG seven-pass G-type receptor 2, member of the class B2 family of ...
94-268 1.24e-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: 43.27  E-value: 1.24e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486  94 LSVKALYTVGYSTSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLrAISVFIkdwiLYAEQDSNhcfisTVECKAVM 173
Cdd:cd15992    2 LPLKTLTWSSVGVTLGFLLLTFLFLLCLRALRSNKTSIRKNGATALFL-SELVFI----LGINQADN-----PFACTVIA 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 174 VFFHYCVVSNYFWLFIEGLYLFTLLVE----TFFPERRYFywytIIGWGTPTVCVTVWATL--RLYFDDTGCWdMNDSTA 247
Cdd:cd15992   72 ILLHFFYLCTFSWLFLEGLHIYRMLSEvrdiNYGPMRFYY----LIGWGVPAFITGLAVGLdpEGYGNPDFCW-LSIYDT 146
                        170       180
                 ....*....|....*....|.
gi 530384486 248 LWWVIKGPVVGSIMVNFVLFI 268
Cdd:cd15992  147 LIWSFAGPVAFAVSMNVFLYI 167
7tmB2_BAI3 cd15989
brain-specific angiogenesis inhibitor 3, a group VII adhesion GPCR, member of the class B2 ...
106-360 1.80e-04

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: 43.13  E-value: 1.80e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 106 TSLVTLTTAMVILCRFRKLHCTRNFIHMNLFVSFMLRAISVFIKdwilyaeQDSNHcfiSTVECKAVMVFFHYCVVSNYF 185
Cdd:cd15989   17 SCLALITLAVVYAALWRYIRSERSIILINFCLSIISSNILILVG-------QTQTH---NKGICTMTTAFLHFFFLASFC 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 186 WLFIEGLYLFTLL---VETFFPERRYFywytIIGWGTPTVCVTV---WATLRLYFDDTGCWdMNDSTALWWVIKGPVVGS 259
Cdd:cd15989   87 WVLTEAWQSYMAVtgkIRTRLIRKRFL----CLGWGLPALVVAIsmgFTKAKGYGTPHYCW-LSLEGGLLYAFVGPAAAV 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 260 IMVNFVlfIGIIV---------ILVQKLQ--SPDMGGNESSIYLRLAR----------------------STLLLIPLFG 306
Cdd:cd15989  162 VLVNMV--IGILVfnklvsrdgILDKKLKhrAGQMSEPHSGLTLKCAKcgvvsttalsattasnamaslwSSCVVLPLLA 239
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 530384486 307 IHYTVFAFSpenVSKRERLVFELGLGSF---QGFVVAVLYCFLNGEVQAEIKRKWRS 360
Cdd:cd15989  240 LTWMSAVLA---MTDKRSILFQILFAVFdslQGFVIVMVHCILRREVQDAFRCRLRN 293
7tmB2_BAI1 cd15990
brain-specific angiogenesis inhibitor 1, a group VII adhesion GPCR, member of the class B2 ...
167-355 2.76e-04

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: 42.28  E-value: 2.76e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 167 VECKAVMVFFHYCVVSNYFWLFIEGLYLFtLLVETFFPERRYFYWYTIIGWGTPTVCVTV---WATLRLYFDDTGCWdMN 243
Cdd:cd15990   69 VVCTLVAAFLHFFFLSSFCWVLTEAWQSY-MAVTGRLRNRIIRKRFLCLGWGLPALVVAIsvgFTKAKGYGTVNYCW-LS 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530384486 244 DSTALWWVIKGPVVGSIMVNFVLFIGIIVILVQKLQSPDMGGNE---SSIYlrlarSTLLLIPLFGIHYTVFAFSpenVS 320
Cdd:cd15990  147 LEGGLLYAFVGPAAAVVLVNMVIGILVFNKLVSKDGITDKKLKEragASLW-----SSCVVLPLLALTWMSAVLA---IT 218
                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 530384486 321 KRERLVFELGLG---SFQGFVVAVLYCFLNGEVQAEIK 355
Cdd:cd15990  219 DRRSALFQILFAvfdSLEGFVIVMVHCILRREVQDAVK 256
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH