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Conserved domains on  [gi|119595553|gb|EAW75147|]
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frizzled homolog 4 (Drosophila) [Homo sapiens]

Protein Classification

frizzled family protein; olfactory receptor( domain architecture ID 11575543)

frizzled family protein similar to the ten frizzleds (Fzd1-10) and smoothened (Smo), which are involved in transmitting the signals of Wnts and hedgehog proteins and are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors; contains an N-terminal extracellular cysteine-rich domain (CRD) associated with their role in binding to Wnt ligands; olfactory receptor plays a central role in olfaction or the sense of smell, similar to human family 6 olfactory receptors; belongs to the class A rhodopsin-like family of G protein-coupled receptors; binding of an odorant to the olfactory receptor induces a conformational change that leads to the activation of the olfactory-specific G protein (Golf)

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
212-512 0e+00

class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 4 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


:

Pssm-ID: 320166  Cd Length: 304  Bit Score: 571.32  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 212 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 291
Cdd:cd15038    1 GLFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRFKYPERPIIFLSMCYNIYSIAYIVRLLAGRESISCDLDSQT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 292 E-PVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 370
Cdd:cd15038   81 AvSILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWFLAAGLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVMRV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 371 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 450
Cdd:cd15038  161 VDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQLQRDGTKTDKLERLMVRIGIFSVLYTVP 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 119595553 451 ATCVIACYFYEISNWALFRYS--ADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 512
Cdd:cd15038  241 ATCVIACYFYEYSNRDLWYYGgsAARPNMEVFMLKIFMSLVVGITSGMWIWSAKTLSSWRNFFN 304
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
45-170 8.77e-97

Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 4 (Fz4) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and the Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Frizzled 4 (Fz4) activates the Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C of the Wnt/Ca(2+) signaling pathway during retinal angiogenesis. Mutations in Fz4 lead to familial exudative vitreoretinopathy (FEVR), a hereditary ocular disorder characterized by failure of the peripheral retinal vascularization. In addition, the interplay between Fz4 and norrin as a receptor-ligand pair plays an important role in vascular development in the retina and inner ear in a Wnt-independent manner.


:

Pssm-ID: 143557  Cd Length: 126  Bit Score: 289.36  E-value: 8.77e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  45 ERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 124
Cdd:cd07448    1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPVPIGPCRPLC 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 119595553 125 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGDEEV 170
Cdd:cd07448   81 LSVKKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGPGDEEV 126
 
Name Accession Description Interval E-value
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
212-512 0e+00

class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 4 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320166  Cd Length: 304  Bit Score: 571.32  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 212 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 291
Cdd:cd15038    1 GLFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRFKYPERPIIFLSMCYNIYSIAYIVRLLAGRESISCDLDSQT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 292 E-PVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 370
Cdd:cd15038   81 AvSILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWFLAAGLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVMRV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 371 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 450
Cdd:cd15038  161 VDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQLQRDGTKTDKLERLMVRIGIFSVLYTVP 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 119595553 451 ATCVIACYFYEISNWALFRYS--ADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 512
Cdd:cd15038  241 ATCVIACYFYEYSNRDLWYYGgsAARPNMEVFMLKIFMSLVVGITSGMWIWSAKTLSSWRNFFN 304
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
213-514 2.21e-173

Frizzled/Smoothened family membrane region; This family contains the membrane spanning region of frizzled and smoothened receptors. This membrane region is predicted to contain seven transmembrane alpha helices. Proteins related to Drosophila frizzled are receptors for Wnt (mediating the beta-catenin signalling pathway), but also the planar cell polarity (PCP) pathway and the Wnt/calcium pathway. The predominantly alpha-helical Cys-rich ligand-binding region (CRD) of Frizzled is both necessary and sufficient for Wnt binding. The smoothened receptor mediates hedgehog signalling.


Pssm-ID: 460242  Cd Length: 321  Bit Score: 492.12  E-value: 2.21e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  213 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFE-EAA 291
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDWSRFRYPERPIIFLSLCYLLVSLGYLIRFVLGREDIACRKDgTGR 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  292 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 371
Cdd:pfam01534  81 GSYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAAGLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLALGKV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  372 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTK-TDKLERLMVKIGVFSVLYTVP 450
Cdd:pfam01534 161 DGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLKKDGARaTDKLEKLMVRIGVFSVLYTVP 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  451 ATCVIACYFYEISN-------WALFRYSADDS----------NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNR 513
Cdd:pfam01534 241 ALIVIACYFYEYANrdswelsWQYINCRAYGIpcldepesrpSFSVFMLKYFMSLVVGITSGFWVWSGKTLESWRRFFRR 320

                  .
gi 119595553  514 L 514
Cdd:pfam01534 321 L 321
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
45-170 8.77e-97

Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 4 (Fz4) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and the Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Frizzled 4 (Fz4) activates the Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C of the Wnt/Ca(2+) signaling pathway during retinal angiogenesis. Mutations in Fz4 lead to familial exudative vitreoretinopathy (FEVR), a hereditary ocular disorder characterized by failure of the peripheral retinal vascularization. In addition, the interplay between Fz4 and norrin as a receptor-ligand pair plays an important role in vascular development in the retina and inner ear in a Wnt-independent manner.


Pssm-ID: 143557  Cd Length: 126  Bit Score: 289.36  E-value: 8.77e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  45 ERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 124
Cdd:cd07448    1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPVPIGPCRPLC 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 119595553 125 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGDEEV 170
Cdd:cd07448   81 LSVKKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGPGDEEV 126
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
48-164 2.11e-52

Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell along the anteroposterior axis. Homologues of the N-terminal region of frizzled exist either as transmembrane or secreted molecules. Frizzled homologues are reported to be receptors for the Wnt growth factors. (Not yet in MEDLINE: the FRI domain occurs in several receptor tyrosine kinases [Xu, Y.K. and Nusse, Curr. Biol. 8 R405-R406 (1998); Masiakowski, P. and Yanopoulos, G.D., Curr. Biol. 8, R407 (1998)].


Pssm-ID: 214498  Cd Length: 113  Bit Score: 173.65  E-value: 2.11e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553    48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINiPIGPCGGMCLSV 127
Cdd:smart00063   1 CEPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDLR-PILPCRSLCEAA 79
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 119595553   128 KRRCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCMEG 164
Cdd:smart00063  80 REGCEPLMEKFGFPWPEFLRCDRFPVQEE---LCMDP 113
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
48-154 3.09e-37

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.


Pssm-ID: 460190  Cd Length: 116  Bit Score: 133.46  E-value: 3.09e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553   48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQ-----LTTFTPLIQYGCSSQLQFFLCSVYVPMCT--EKINIPIGPC 120
Cdd:pfam01392   1 CEPITLPMCLGLGYNATVFPNLLGHQTQEEAELSlaylvLSEFEPLVDLSCSPSLRLFLCSLYFPPCTlgPSPKPVCPPC 80
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 119595553  121 GGMCLSVKRRCEPVL--KEFGFAWPESLNCSKFPPQ 154
Cdd:pfam01392  81 RSLCEEVRYGCEPLLeeAKFGFSWPEFLDCDSLPAD 116
 
Name Accession Description Interval E-value
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
212-512 0e+00

class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 4 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320166  Cd Length: 304  Bit Score: 571.32  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 212 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 291
Cdd:cd15038    1 GLFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRFKYPERPIIFLSMCYNIYSIAYIVRLLAGRESISCDLDSQT 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 292 E-PVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 370
Cdd:cd15038   81 AvSILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWFLAAGLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVMRV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 371 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 450
Cdd:cd15038  161 VDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQLQRDGTKTDKLERLMVRIGIFSVLYTVP 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 119595553 451 ATCVIACYFYEISNWALFRYS--ADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 512
Cdd:cd15038  241 ATCVIACYFYEYSNRDLWYYGgsAARPNMEVFMLKIFMSLVVGITSGMWIWSAKTLSSWRNFFN 304
7tmF_FZD4_9_10-like cd15909
class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G ...
212-512 0e+00

class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 4, 9 and 10 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320575  Cd Length: 320  Bit Score: 534.58  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 212 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 291
Cdd:cd15909    1 VMFSRSDKNFAEIWMAVWASLCFASTAFTVLTFLIDTSRFRYPERPIIFLSMCYFIYSLGYLIRLFLGRERIACDSLNSG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 292 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 371
Cdd:cd15909   81 VSYLIQEGLESTWCTIVFLLLYYFGMASALWWVILTFTWYLAAGRKWGPEAIEAASSYFHLVAWALPAVKTIVILIMHKV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 372 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 451
Cdd:cd15909  161 DADELTGLCYVGNHDSDALLGFVLVPLAIYLLIGTLFILAGFVSMFRIRRNLKTRGTDTSKLEKLMVKIGVFSVLYTVPA 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 452 TCVIACYFYEISNWALFRYSA-------------------DDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 512
Cdd:cd15909  241 TCVIACYFYEYLNMDQWRIAAieckcqspnaigsdcclqpSIPSVEIYMLKIFMSLVVGITSGMWVWSSKTLQSWQRFIC 320
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
213-514 2.21e-173

Frizzled/Smoothened family membrane region; This family contains the membrane spanning region of frizzled and smoothened receptors. This membrane region is predicted to contain seven transmembrane alpha helices. Proteins related to Drosophila frizzled are receptors for Wnt (mediating the beta-catenin signalling pathway), but also the planar cell polarity (PCP) pathway and the Wnt/calcium pathway. The predominantly alpha-helical Cys-rich ligand-binding region (CRD) of Frizzled is both necessary and sufficient for Wnt binding. The smoothened receptor mediates hedgehog signalling.


Pssm-ID: 460242  Cd Length: 321  Bit Score: 492.12  E-value: 2.21e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  213 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFE-EAA 291
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDWSRFRYPERPIIFLSLCYLLVSLGYLIRFVLGREDIACRKDgTGR 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  292 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 371
Cdd:pfam01534  81 GSYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAAGLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLALGKV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  372 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTK-TDKLERLMVKIGVFSVLYTVP 450
Cdd:pfam01534 161 DGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLKKDGARaTDKLEKLMVRIGVFSVLYTVP 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  451 ATCVIACYFYEISN-------WALFRYSADDS----------NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNR 513
Cdd:pfam01534 241 ALIVIACYFYEYANrdswelsWQYINCRAYGIpcldepesrpSFSVFMLKYFMSLVVGITSGFWVWSGKTLESWRRFFRR 320

                  .
gi 119595553  514 L 514
Cdd:pfam01534 321 L 321
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
214-508 4.64e-158

class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 9 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320164  Cd Length: 320  Bit Score: 453.26  E-value: 4.64e-158
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 214 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDfEEAAEP 293
Cdd:cd15036    3 WSRGDKDFALVWMAVWSTLCFVSTAFTVLTFLLDPHRFQYPERPIIFLSMCYNVYSVAFLIRAVAGAESIACD-RENGAL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 294 VLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDA 373
Cdd:cd15036   82 YIIQEGLESTGCTLVFLILYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIESHGSYFHMAAWGIPALKTIVILTMRKVAG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 374 DELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATC 453
Cdd:cd15036  162 DELTGLCYVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKVMKTGGTNTEKLEKLMVKIGVFSILYTVPATC 241
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119595553 454 VIACYFYEISNWALFRYSADDS--------------------NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQ 508
Cdd:cd15036  242 VIVCYFYERLNMDYWDLRALEEscrtvpgrrrpdcslphsvpTVAVFMLKIFMSLVVGITSGVWVWSSKTLQTWQ 316
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
212-510 5.97e-156

class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor superfamily; The class F G protein-coupled receptors includes the frizzled (FZD) family of seven-transmembrane proteins consisting of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. Also included in the class F family is the closely related smoothened (SMO), which is a transmembrane G protein-coupled receptor that acts as the transducer of the hedgehog (HH) signaling pathway. SMO is activated by the hedgehog (HH) family of proteins acting on the 12-transmembrane domain receptor patched (PTCH), which constitutively inhibits SMO. Thus, in the absence of HH proteins, PTCH inhibits SMO signaling. On the other hand, binding of HH to the PTCH receptor activates its internalization and degradation, thereby releasing the PTCH inhibition of SMO. This allows SMO to trigger intracellular signaling and the subsequent activation of the Gli family of zinc finger transcriptional factors and induction of HH target gene expression (PTCH, Gli1, cyclin, Bcl-2, etc). The WNT and HH signaling pathways play critical roles in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320089  Cd Length: 314  Bit Score: 447.54  E-value: 5.97e-156
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 212 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 291
Cdd:cd13951    1 GLFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSRFRYPERPIIFLALCYNFYSLGYLVRLVVGREGIACGKDEGK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 292 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 371
Cdd:cd13951   81 PYLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSSEAIEKKSSYFHLVAWGLPAVLTIAVLVLRKV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 372 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 451
Cdd:cd13951  161 DGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSILSNDGKKTDKLEKLMLRIGIFAVLYTLPA 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119595553 452 TCVIACYFYEISNWALFRYS-------------ADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKC 510
Cdd:cd13951  241 LIVIACYFYEYANRPDWLRSwephsccspdceiLSRPSLAVFLLKYFMQLVIGITTGVWVWSKKTLLSWRRL 312
7tmF_FZD1_2_7-like cd15034
class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; ...
213-509 7.25e-148

class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 1, 2 and 7 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of G-protein coupled receptors, as well as their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320162  Cd Length: 322  Bit Score: 427.14  E-value: 7.25e-148
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 213 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISC-DFEEAA 291
Cdd:cd15034    2 FFTEKEREFARLWIGIWSVLCAASTLFTVLTFLIDMDRFRYPERPIIFLSGCYFMVSIAYIVGFFLG-DKVACnGPFPPG 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 292 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 371
Cdd:cd15034   81 GPKTVTQGTKKEGCTILFMMLYFFSMASSIWWVILTLTWFLAAGLKWGHEAIEANSQYFHLAAWAVPAIKTIAILAMGKV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 372 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 451
Cdd:cd15034  161 DGDVLSGVCFVGLSDVDALRGFVLAPLFVYLLIGTSFLLAGFVSLFRIRTVMKHDGTKTDKLEKLMVRIGVFSVLYTVPA 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119595553 452 TCVIACYFYEISN---WALFRYSA------------------DDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQK 509
Cdd:cd15034  241 TIVIACYFYEQANresWEKSWLSQnckkyedpcpcpptphplDRPDFTVFMIKYLMTLIVGITSGFWIWSGKTLQSWRQ 319
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
214-510 9.43e-148

class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 5 and 8 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, as well as their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320163  Cd Length: 307  Bit Score: 426.31  E-value: 9.43e-148
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 214 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEeaaep 293
Cdd:cd15035    3 FSEDEKTFATFWIGLWSILCFISTLITVLTFLIDMQRFQYPERPIIFLSFCYFMVSVGYIIRLIVGHEAVACDGG----- 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 294 vLIQEGLknTG---CAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 370
Cdd:cd15035   78 -IIRYAT--TGpalCTVVFLLTYFFGMASSIWWVILSLTWFLAAGLKWGNEAISSYSQYFHLVAWLIPAVQTIAILALSA 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 371 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDG-TKTDKLERLMVKIGVFSVLYTV 449
Cdd:cd15035  155 VDGDPISGICYVGNQNLNNLRGFVLAPLVVYLILGTSFLLAGFVSLFRIRNVIKQQGgDKTDKLEKLMIRIGIFSVLYTV 234
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119595553 450 PATCVIACYFYEISN---WAL-------FRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKC 510
Cdd:cd15035  235 PATIVIACYFYEQHYreiWEKslncpcsPGSIKSRPEYSIFMLKYFMSLVVGITSGFWIWSGKTLDSWKRF 305
7tmF_FZD10 cd15037
class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This ...
214-508 3.81e-142

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


Pssm-ID: 320165  Cd Length: 320  Bit Score: 412.84  E-value: 3.81e-142
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 214 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDfEEAAEP 293
Cdd:cd15037    3 WSKDDKRFAVVWIAIWSILCFFSSAFTVLTFLIDPQRFKYPERPIIFLSMCYCVYSVGYIIRLFAGAESIACD-RDSGQL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 294 VLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDA 373
Cdd:cd15037   82 YVIQEGLESTGCTIVFLILYYFGMASSLWWVILTLTWFLAAGKKWGHEAIEANSSYFHLAAWAIPAVKTIMILVMRRVAG 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 374 DELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATC 453
Cdd:cd15037  162 DELTGVCYVGSMDVNALTGFVLIPLACYLIIGTSFILSGFVALFHIRRVMKTGGENTDKLEKLMVRIGVFSVLYTVPATC 241
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119595553 454 VIACYFYEISN---WALF----------RYSADDSNM-----AVE--MLKIFMSLLVGITSGMWIWSAKTLHTWQ 508
Cdd:cd15037  242 VIACYFYERLNmdyWKILatqqkckmdnQTKTLDCVMtssipAVEifMVKIFMLLVVGITSGMWIWTSKTLQSWQ 316
7tmF_FZD5 cd15249
class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This ...
214-509 7.74e-127

class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 5 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320377  Cd Length: 310  Bit Score: 373.12  E-value: 7.74e-127
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 214 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFE----- 288
Cdd:cd15249    3 FSQDERTFATFWIGLWSVLCFISTFTTVATFLIDMERFRYPERPIIFLSACYLFVSLGYIVRLVVGHESVACNREhnhih 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 289 -EAAEPVLiqeglkntgCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILI 367
Cdd:cd15249   83 yETTGPAL---------CTIVFLLIYFFGMASSIWWVILSFTWFLAAGMKWGNEAIAGYSQYFHLAAWLIPSVKSIAVLA 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 368 MRLVDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLY 447
Cdd:cd15249  154 LSSVDGDPVAGICYVGNQNLNNLRGFVLAPLVVYLFTGTLFLLAGFVSLFRIRSVIKQGGTKTDKLEKLMIRIGIFTVLY 233
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119595553 448 TVPATCVIACYFYEI---SNW------------ALFRYSADdsnMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQK 509
Cdd:cd15249  234 TVPATIVVACYVYEQhyrESWeaalncscpgddTQPRARPD---YAVFMLKYFMCLVVGITSGVWIWSGKTLESWRR 307
7tmF_FZD7 cd15246
class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This ...
214-519 1.56e-125

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


Pssm-ID: 320374  Cd Length: 331  Bit Score: 370.89  E-value: 1.56e-125
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 214 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgRERISC--DFEEAA 291
Cdd:cd15246    3 FKEEEVRFARLWVGIWSILCCASTLFTVLTYLVDMRRFSYPERPIIFLSGCYFMVAVAYAAGFLL-EDRVVCveRFSDDG 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 292 EPVLIQeGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 371
Cdd:cd15246   82 YRTVAQ-GTKKEGCTILFMVLYFFGMASSIWWVILSLTWFLSAGMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMGQV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 372 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 451
Cdd:cd15246  161 DGDLLSGVCYVGIYSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIGVFSVLYTVPA 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 452 TCVIACYFYEIS-------NWAL------------FRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 512
Cdd:cd15246  241 TIVLACYFYEQAfretwekTWLLqtckryavpcpnNNFAPMSPDFTVFMIKYLMTMIVGITSGFWIWSGKTLQSWRRFYH 320

                 ....*..
gi 119595553 513 RLVNSGK 519
Cdd:cd15246  321 RLSNGSK 327
7tmF_FZD8 cd15250
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This ...
214-508 1.61e-124

class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 8 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320378  Cd Length: 314  Bit Score: 367.33  E-value: 1.61e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 214 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAAEP 293
Cdd:cd15250    3 FSQEERTFTAFWIGLWSVLCFLSTFATVSTFLIDMERFKYPERPIIFLSACYLFVSLGYLVRLIAGHEKVACSRGALAEV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 294 VLIQegLKNTG---CAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 370
Cdd:cd15250   83 EHIH--YETTGpalCTVVFLLIYFFGMASSIWWVILSLTWFLAAGMKWGNEAIAGYSQYFHLAAWLIPSVKSIAVLALSS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 371 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 450
Cdd:cd15250  161 VDGDPVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVSLFRIRSVIKQGGTKTDKLEKLMIRIGIFTVLYTVP 240
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 451 ATCVIACYFYEISN---WAL---------FRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQ 508
Cdd:cd15250  241 ATIVVACYFYEQHNrqrWEIthncnclrdQPDQARRPDYAVFMLKYFMCLVVGITSGVWTWSGKTLESWR 310
7tmF_FZD2 cd15245
class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This ...
213-519 3.95e-124

class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 2 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of G-protein coupled receptors. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320373  Cd Length: 330  Bit Score: 367.04  E-value: 3.95e-124
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 213 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISCD--FEEA 290
Cdd:cd15245    2 FFSQDEIRFARIWILIWSVLCCASTFFTVTTYLVDMQRFRYPERPIIFLSGCYTMVSVAYIAGFVLG-DKVVCNerFSED 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 291 AEPVLIQeGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 370
Cdd:cd15245   81 GYKTVVQ-GTKKEGCTILFMMLYFFSMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMGQ 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 371 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 450
Cdd:cd15245  160 IDGDLLSGVCFVGLNNIDPLRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLERLMVRIGVFSVLYTVP 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 451 ATCVIACYFYEIS---NWALFRYSADDSNMA----------------VEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCS 511
Cdd:cd15245  240 ATIVIACYFYEQAfrqHWERSWISQNCKSLAipcplqytprmtpdftVYMIKYLMTLIVGITSGFWIWSGKTLHSWRKFY 319

                 ....*...
gi 119595553 512 NRLVNSGK 519
Cdd:cd15245  320 TRLTNSRQ 327
7tmF_FZD1_insect cd15248
class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
214-514 1.07e-118

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


Pssm-ID: 320376  Cd Length: 332  Bit Score: 353.35  E-value: 1.07e-118
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 214 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISC-------- 285
Cdd:cd15248    3 FPERERTFSRYWIGSWAAVCMASCLFTVLTFLIDSSRFRYPERPIVFLSVCYLMVAAAYVAGLGAG-DSVSCnepfpppv 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 286 DFEEAAEPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVI 365
Cdd:cd15248   82 KLGRLQMVSTITQGTKTESCTVLFMVLYFFSMAASIWWVVLTLTWFLAAGLKWGHEAIEAKSHYFHLVAWAVPALKTISI 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 366 LIMRLVDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSV 445
Cdd:cd15248  162 LAMGKVEGDVLSGVCYVGLWDMHALRGFVLAPLCVYLSLGTIFLLAGFISLFRIRTVMKHDGTKTDKLEKLMLRIGIFSF 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 446 LYTVPATCVIACYFYEISN---WAL---------FRYSA----------DDSNMAVEMLKIFMSLLVGITSGMWIWSAKT 503
Cdd:cd15248  242 LYTLPALIVLACLFYEQAHfdsWMLqwhrdickpPSWSIpacratgspeARPEFQVFMIKYLMSMIVGITSSVWIWSSKT 321
                        330
                 ....*....|.
gi 119595553 504 LHTWQKCSNRL 514
Cdd:cd15248  322 LVSWRNFYERL 332
7tmF_FZD1 cd15247
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
220-517 1.15e-118

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


Pssm-ID: 320375  Cd Length: 341  Bit Score: 353.58  E-value: 1.15e-118
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 220 EFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgRERISCD--FEEAAEPVLIQ 297
Cdd:cd15247   19 RFARIWIGIWSVLCCASTLFTVLTYLVDMKRFSYPERPIIFLSGCYTMVAIAYIAGFLL-EDKVVCNdkFAEDGIKTVAQ 97
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 298 eGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELT 377
Cdd:cd15247   98 -GTKKEGCTILFMMLYFFSMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAIKTITILAVGQVDGDVLS 176
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 378 GLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVIAC 457
Cdd:cd15247  177 GVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIGIFSVLYTVPATIVIAC 256
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119595553 458 YFYE---------------ISNWALFRYSADDSNMA----VEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNRLVNS 517
Cdd:cd15247  257 YFYEqafreqwerswisqsCKTYAIPCPAHSHPPMSpdftVFMIKYLMTLIVGITSGFWIWSGKTLNSWRKFYTRLTNS 335
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
45-170 8.77e-97

Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 4 (Fz4) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and the Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Frizzled 4 (Fz4) activates the Ca(2+)/calmodulin-dependent protein kinase II and protein kinase C of the Wnt/Ca(2+) signaling pathway during retinal angiogenesis. Mutations in Fz4 lead to familial exudative vitreoretinopathy (FEVR), a hereditary ocular disorder characterized by failure of the peripheral retinal vascularization. In addition, the interplay between Fz4 and norrin as a receptor-ligand pair plays an important role in vascular development in the retina and inner ear in a Wnt-independent manner.


Pssm-ID: 143557  Cd Length: 126  Bit Score: 289.36  E-value: 8.77e-97
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  45 ERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 124
Cdd:cd07448    1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPVPIGPCRPLC 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 119595553 125 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGDEEV 170
Cdd:cd07448   81 LSVKKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGPGDEEV 126
7tmF_FZD3_FZD6-like cd15910
class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G ...
220-507 1.66e-80

class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G protein-coupled receptors; This group includes subfamilies 3 and 6 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and their closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320576  Cd Length: 321  Bit Score: 254.78  E-value: 1.66e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 220 EFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISCDFEEAAEPV--LIQ 297
Cdd:cd15910    9 MFARYFIGVVSILCLLATLFTFLTFLIDVNRFRYPERPIIFYAVCYFVVSLIFFVGFLLG-DDVACNHAIMDENNgaTVV 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 298 EGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELT 377
Cdd:cd15910   88 EGSRNKACTILFMILYFFTMAGTVWWVILTITWFLAAGFKWGSEAIEKKALYFHALAWGIPGVLTMVLLATNKIEGDNIS 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 378 GLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVIAC 457
Cdd:cd15910  168 GVCFVGLYDSDGLRFFVLLPLCLYVLVGMSLLLAGIICLNRVRKSIHDDETNQEKLAKFMIRIGVFSILYLVPLLTLIGC 247
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119595553 458 YFYEISN-------WALFR---------YSADDS---NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTW 507
Cdd:cd15910  248 YAYEQSNrkswestWVVRNcrryhipcpQLAQGNprpGLFLFCIKYLMTLIVGIPPVFWVGSKKTCAEW 316
7tmF_FZD3 cd15033
class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This ...
214-507 3.52e-78

class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This group includes subfamily 3 of the frizzled (FZD) family of seven transmembrane-spanning proteins, which constitute a novel and separate class of GPCRs, and its closely related proteins. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320161  Cd Length: 321  Bit Score: 248.71  E-value: 3.52e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 214 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgRERISCDFEEAAE- 292
Cdd:cd15033    3 FRREELSFARYFIGVISIVCLSATLFTFLTFLIDVTRFRYPERPIIFYAVCYMMVSLIFFIGFLL-EDRVACNAASPGQy 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 293 -PVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 371
Cdd:cd15033   82 kASTVTQGSHNKACTMLFMVLYFFTMAGSVWWVILTITWFLAAVPKWGSEAIEKKALLFHASAWGIPGTLTIILLAMNKI 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 372 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 451
Cdd:cd15033  162 EGDNISGVCFVGLYDVDALRYFVLAPLCLDVVVGVSLLLAGIISLNRVRIEIPLEKENQDKLVKFMIRIGVFSVLYLVPL 241
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119595553 452 TCVIACYFYEIS-------NWALFR---------YSADDS---NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTW 507
Cdd:cd15033  242 LVVIGCYFYEQAyrgvwetTWVQERcreyhipcpYKVTQTsrpDLILFLMKYLMALVVGIPSVFWVGSKKTCFEW 316
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
220-507 1.92e-72

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


Pssm-ID: 320160  Cd Length: 321  Bit Score: 233.59  E-value: 1.92e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 220 EFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISCDFE----EAAEPVL 295
Cdd:cd15032    9 DFAKSFIGIVSIFCLCATLFTFLTFLIDVKRFRYPERPIIYYSVCYSIVSLMYFIGFLLG-NSTACNKAdeklELGDTVV 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 296 IqeGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADE 375
Cdd:cd15032   88 L--GSQNKACTVLFMLLYFFTMAGTIWWVILTITWFLAAGRKWSCEAIEQKALWFHAVAWGIPGFLTIMLLAMNKVEGDN 165
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 376 LTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVI 455
Cdd:cd15032  166 ISGVCFVGLYDLDASRYFVLLPLCLCVFVGLSLLLAGIISLNHVRQVIQHDGRNQEKLKKFMIRIGVFSGLYLVPLVTLL 245
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119595553 456 ACYFYEISN---WA---LFRYSADDS-------------NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTW 507
Cdd:cd15032  246 GCYVYEQVYrrtWEitwVSDHCQQYHipcpyqakavarpELALFLIKYLMTLIVGISAVFWVGSKKTCSEW 316
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
224-509 4.21e-58

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


Pssm-ID: 320158  Cd Length: 331  Bit Score: 196.36  E-value: 4.21e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 224 IWMAVWASLCFISTAFTVLTFLID---SSRfsYPERPIIFLSMCYNIYSIAYIVRLTVG-RERISC---DFEEAAEPvli 296
Cdd:cd15030   13 KFIAVFASVCLLCTLFTVLTFFIDwknSNR--YPAVILFYINACFFIGSIGWLAQFLPGaREDIVCrkdGTMRLGEP--- 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 297 QEGlKNTGCAIIFLLMYFFGMASSIWWVILTLTW---FLAAGLKwgHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDA 373
Cdd:cd15030   88 SAG-ENLSCVVIFVLVYYFLMAGCVWFVILTYAWhmsFKALGTI--QDRLDKKTAYFHLIAWSLPLVLTITIMALGQVDG 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 374 DELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSN---LQKDGTKTdKLERLMVKIGVFSVLYTVP 450
Cdd:cd15030  165 DSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISspeILSEKASS-KIRETIVRLGIFAFLALGF 243
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 451 ATCVIACYFYEISN---WAL-FR-------------YSADDS---------NMAVEMLKIFMSLLVGITSGMWIWSAKTL 504
Cdd:cd15030  244 VLITFACHVYEFFNqaeWEKsFRdyivceanvtiaeQTNGDIpecelksrpSLAMLQLHLLALFGAGIAMSSWVWTRATL 323

                 ....*
gi 119595553 505 HTWQK 509
Cdd:cd15030  324 ETWKR 328
7tmF_FZD3_insect cd15031
class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; ...
213-511 5.93e-58

class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This group represents subfamily 3 of the frizzled (FZD) family of seven transmembrane-spanning G protein-coupled proteins that is found in insects such as Drosophila melanogaster. This class F protein family consists of 10 isoforms (FZD1-10) in mammals. The FZDs are activated by the wingless/int-1 (WNT) family of secreted lipoglycoproteins and preferentially couple to stimulatory G proteins of the Gs family, which activate adenylate cyclase, but can also couple to G proteins of the Gi/Gq families. In the WNT/beta-catenin signaling pathway, the WNT ligand binds to FZD and a lipoprotein receptor-related protein (LRP) co-receptor. This leads to the stabilization and translocation of beta-catenin to the nucleus, where it induces the activation of TCF/LEF family transcription factors. The conserved cytoplasmic motif of FZD, Lys-Thr-X-X-X-Trp, is required for activation of the WNT/beta-catenin pathway, and for membrane localization and phosphorylation of Dsh (dishevelled) protein, a key component of the WNT pathway that relays the WNT signals from the activated receptor to downstream effector proteins. The WNT pathway plays a critical role in many developmental processes, such as cell-fate determination, cell proliferation, neural patterning, stem cell renewal, tissue homeostasis and repair, and tumorigenesis, among many others.


Pssm-ID: 320159  Cd Length: 311  Bit Score: 195.37  E-value: 5.93e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 213 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA- 291
Cdd:cd15031    2 FYTTRQKKLVESWMLVLSAVSFILTLFALVTFWAEPTRFGYPERPVLFMALCYNLISLCYLERGILGTFTNCSARSLAId 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 292 --EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMR 369
Cdd:cd15031   82 cdDRYLRQDCLLTPQCLASFIITYYLSLSAASWWLIFALCWYLSSAKKWSSEALEKKSGLFHVLAWVPPLAPPIAALLLE 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 370 LVDADELTGLCYVGNQNLDALTGFvvaPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKleRLMVKIGVFSVLYTV 449
Cdd:cd15031  162 RVSASELTGTCTASGFVESSISEL---PALILLLLGLYLTIAALRSLLSLQQQLQSRLAHAPQ--RILARVSIFSLLYLI 236
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 119595553 450 PATCVIACYFYEISNWALFRYSADDSNMA------------VEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCS 511
Cdd:cd15031  237 PAAAALICKLCERWLQPVPECNALQEDCAppatdneflsalPALLRVFFFLIGGTATGLWLWSRKSCESWRSRL 310
CRD_FZ10 cd07462
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 10 (Fz10) receptor; The cysteine-rich ...
45-167 3.78e-54

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 10 (Fz10) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 10 (Fz10) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. The cellular functon of Fz10 is unknown.


Pssm-ID: 143571  Cd Length: 127  Bit Score: 179.06  E-value: 3.78e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  45 ERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 124
Cdd:cd07462    2 EGRCQPIEIPMCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQVSTPIPACRVMC 81
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 119595553 125 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGD 167
Cdd:cd07462   82 EQARLKCSPIMEQFNFKWPDSLDCSKLPNKNDPNYLCMEAPNN 124
CRD_FZ9_like cd07457
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich ...
47-165 3.83e-54

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) and frizzled 10 (Fz10) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143566  Cd Length: 121  Bit Score: 178.84  E-value: 3.83e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 126
Cdd:cd07457    2 KCERITIPMCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQVSIPIPACRSMCEQ 81
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 119595553 127 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGP 165
Cdd:cd07457   82 ARDKCSPIMEQFSFSWPDSLDCDRLPRKNDPKDLCMEAP 120
CRD_FZ9 cd07463
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich ...
47-165 4.65e-54

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 9 (Fz9) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz9 may play a signaling role in lymphoid development and maturation, particularly at points where B cells undergo self-renewal prior to further differentiation.


Pssm-ID: 143572  Cd Length: 127  Bit Score: 178.68  E-value: 4.65e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 126
Cdd:cd07463    4 KCQPVVIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQVSTSIPACRPMCEQ 83
                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 119595553 127 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGP 165
Cdd:cd07463   84 ARQKCSPIMEQFNFGWPESLDCSRLPTRNDPNALCMEAP 122
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
48-164 2.11e-52

Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell along the anteroposterior axis. Homologues of the N-terminal region of frizzled exist either as transmembrane or secreted molecules. Frizzled homologues are reported to be receptors for the Wnt growth factors. (Not yet in MEDLINE: the FRI domain occurs in several receptor tyrosine kinases [Xu, Y.K. and Nusse, Curr. Biol. 8 R405-R406 (1998); Masiakowski, P. and Yanopoulos, G.D., Curr. Biol. 8, R407 (1998)].


Pssm-ID: 214498  Cd Length: 113  Bit Score: 173.65  E-value: 2.11e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553    48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINiPIGPCGGMCLSV 127
Cdd:smart00063   1 CEPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDLR-PILPCRSLCEAA 79
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 119595553   128 KRRCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCMEG 164
Cdd:smart00063  80 REGCEPLMEKFGFPWPEFLRCDRFPVQEE---LCMDP 113
CRD_FZ1_like cd07458
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich ...
46-163 2.20e-45

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 1 (Fz1), frizzled 2 (Fz2), and frizzled 7 (Fz7) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143567  Cd Length: 119  Bit Score: 155.65  E-value: 2.20e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  46 RRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTeKINIPIGPCGGMCL 125
Cdd:cd07458    1 GKCEPITIPLCTDIPYNMTIFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCT-VLERPIPPCRSLCE 79
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 119595553 126 SVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNhMCME 163
Cdd:cd07458   80 SARQGCEALMNKFGFQWPESLDCEKFPVHGAGD-LCVG 116
CRD_FZ cd07066
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
47-166 2.40e-45

CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential component of a number of cell surface receptors, which are involved in multiple signal transduction pathways, particularly in modulating the activity of the Wnt proteins, which play a fundamental role in the early development of metazoans. CRD is also found in secreted frizzled related proteins (SFRPs), which lack the transmembrane segment found in the frizzled protein. The CRD domain is also present in the alpha-1 chain of mouse type XVIII collagen, in carboxypeptidase Z, several receptor tyrosine kinases, and the mosaic transmembrane serine protease corin. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. CRD domains have also been identified in multiple tandem copies in a Dictyostelium discoideum protein. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143549  Cd Length: 119  Bit Score: 155.36  E-value: 2.40e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 126
Cdd:cd07066    1 KCEPIPLPLCRGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTPDGDRPIPPCRSLCEE 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 119595553 127 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDhNHMCMEGPG 166
Cdd:cd07066   81 VRDSCEPLMLAFGFPWPEPLDCDRFPDSNE-EGLCISPPG 119
CRD_FZ5_like cd07456
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich ...
47-166 1.32e-40

Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 5 (Fz5) and frizzled 8 (Fz8) receptors, and similar proteins. This domain is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines.


Pssm-ID: 143565  Cd Length: 120  Bit Score: 142.54  E-value: 1.32e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 126
Cdd:cd07456    1 KCEEITIPMCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYDKPLPPCRSVCER 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 119595553 127 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPG 166
Cdd:cd07456   81 ARDGCAPIMRQYGFAWPERMSCDALPEGGDPDNLCMDRNN 120
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
48-154 3.09e-37

Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups. The domain contains 10 conserved cysteines.


Pssm-ID: 460190  Cd Length: 116  Bit Score: 133.46  E-value: 3.09e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553   48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQ-----LTTFTPLIQYGCSSQLQFFLCSVYVPMCT--EKINIPIGPC 120
Cdd:pfam01392   1 CEPITLPMCLGLGYNATVFPNLLGHQTQEEAELSlaylvLSEFEPLVDLSCSPSLRLFLCSLYFPPCTlgPSPKPVCPPC 80
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 119595553  121 GGMCLSVKRRCEPVL--KEFGFAWPESLNCSKFPPQ 154
Cdd:pfam01392  81 RSLCEEVRYGCEPLLeeAKFGFSWPEFLDCDSLPAD 116
CRD_FZ8 cd07461
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich ...
44-163 8.19e-37

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 8 (Fz8) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Xenopus Fz8 is important in Wnt/beta-catenin signaling pathways controlling the transcriptional activation of target genes Siamois and Xnr3 in the animal caps of late blastula.


Pssm-ID: 143570  Cd Length: 125  Bit Score: 132.80  E-value: 8.19e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  44 EERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGM 123
Cdd:cd07461    1 KELQCQEITVPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYKKPLPPCRSV 80
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 119595553 124 CLSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCME 163
Cdd:cd07461   81 CERAKAGCAPLMRQYGFPWPDRMRCDLLPEQGNPDTLCMD 120
CRD_FZ5 cd07460
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 5 (Fz5) receptor.proteins; The ...
48-163 3.33e-36

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 5 (Fz5) receptor.proteins; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 5 (Fz5) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz5 plays critical regulating roles in the yolk sac and placental angiogenesis, in the maturation of the Paneth cell phenotype, in governing the neural potential of progenitors in the developing retina, and in neuronal survival in the parafascicular nucleus.


Pssm-ID: 143569 [Multi-domain]  Cd Length: 127  Bit Score: 130.91  E-value: 3.33e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLSV 127
Cdd:cd07460    5 CQEITVPMCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPDYRKPLPPCRSVCERA 84
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 119595553 128 KRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCME 163
Cdd:cd07460   85 KAGCSPLMRQYGFAWPERMNCDRLPVLGDPETLCMD 120
CRD_corin_2 cd07888
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
47-162 8.48e-32

One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ; The cysteine-rich domain (CRD) is an essential component of corin, a type II transmembrane serine protease which functions as the convertase of the pro-atrial natriuretic peptide (pro-ANP) in the heart. Corin contains two CRDs in its extracellular region, which play an important role in recognition of the physiological substrate, pro-ANP. This model characterizes the second (C-terminal) CRD.


Pssm-ID: 143579 [Multi-domain]  Cd Length: 122  Bit Score: 118.96  E-value: 8.48e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAEL--QLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 124
Cdd:cd07888    1 QCEPITLELCMNLPYNTTRYPNYLGHRTQKEASIswESSLFPALVQTNCYKYLMFFACTILVPKCDPVTQQRIPPCRSLC 80
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 119595553 125 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCM 162
Cdd:cd07888   81 RNSKERCESVLGIVGLQWPEDTDCAQFPEENSDNQTCL 118
CRD_FZ2 cd07464
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich ...
48-152 2.83e-31

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 2 (Fz2) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz2 is involved in the Wnt/beta-catenin signaling pathway and in the activation of protein kinase C and calcium/calmodulin-dependent protein kinase (CaM kinase).


Pssm-ID: 143573  Cd Length: 127  Bit Score: 117.50  E-value: 2.83e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTeKINIPIGPCGGMCLSV 127
Cdd:cd07464    5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSLELRFFLCSMYAPVCT-VLEQAIPPCRSICERA 83
                         90       100
                 ....*....|....*....|....*
gi 119595553 128 KRRCEPVLKEFGFAWPESLNCSKFP 152
Cdd:cd07464   84 RQGCEALMNKFGFQWPERLRCENFP 108
CRD_FZ1 cd07465
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich ...
48-152 3.40e-31

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 1 (Fz1) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata.


Pssm-ID: 143574  Cd Length: 127  Bit Score: 117.46  E-value: 3.40e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTeKINIPIGPCGGMCLSV 127
Cdd:cd07465    5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVCT-VLEQALPPCRSLCERA 83
                         90       100
                 ....*....|....*....|....*
gi 119595553 128 KRRCEPVLKEFGFAWPESLNCSKFP 152
Cdd:cd07465   84 RQGCEALMNKFGFQWPDTLRCEKFP 108
CRD_FZ7 cd07466
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich ...
48-152 3.57e-31

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 7 (Fz7) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Xenopus Fz7 is important in Wnt/beta-catenin signaling pathways controlling the transcriptional activation of target genes Siamois and Xnr3 in the animal caps of late blastula.


Pssm-ID: 143575 [Multi-domain]  Cd Length: 125  Bit Score: 117.11  E-value: 3.57e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTeKINIPIGPCGGMCLSV 127
Cdd:cd07466    5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELKFFLCSMYAPVCT-VLEQAIPPCRSLCERA 83
                         90       100
                 ....*....|....*....|....*
gi 119595553 128 KRRCEPVLKEFGFAWPESLNCSKFP 152
Cdd:cd07466   84 RQGCEALMNKFGFQWPERLRCENFP 108
CRD_SFRP3 cd07441
Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt ...
48-152 7.31e-30

Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt antagonist; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), which plays important roles in embryogenesis and postnatal development as an antagonist of Wnt proteins, key players in a number of fundamental cellular processes. SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled proteins (Fz), thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs. SFRP3 regulates Wnt signaling activity in bone development and homeostasis. It is also involved in the control of planar cell polarity.


Pssm-ID: 143550  Cd Length: 126  Bit Score: 113.61  E-value: 7.31e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKI-NIPIGPCGGMCLS 126
Cdd:cd07441    4 CEPVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTIDFqHEPIKPCKSVCER 83
                         90       100
                 ....*....|....*....|....*.
gi 119595553 127 VKRRCEPVLKEFGFAWPESLNCSKFP 152
Cdd:cd07441   84 ARAGCEPVLIRYRHTWPESLACEELP 109
CRD_SFRP4 cd07442
Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The ...
48-152 7.42e-30

Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related Protein 4 (SFRP4), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRDs domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs.


Pssm-ID: 143551  Cd Length: 127  Bit Score: 113.58  E-value: 7.42e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCT-EKINIPIGPCGGMCLS 126
Cdd:cd07442    5 CEAVRIPMCRHMPWNITRMPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICTlEFLYDPIKPCRSVCQR 84
                         90       100
                 ....*....|....*....|....*.
gi 119595553 127 VKRRCEPVLKEFGFAWPESLNCSKFP 152
Cdd:cd07442   85 ARDGCEPIMRRYNHSWPESLACDDLP 110
CRD_SFRP2 cd07446
Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt ...
48-156 1.45e-29

Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt activity; The cysteine-rich-domain (CRD) is an essential part of the secreted frizzled related protein 2 (SFRP2), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs. As a Wnt antagonist, SFRP2 regulates Nkx2.2 expression in the ventral spinal cord and anteroposterior axis elongation. SFRP2 also has a Wnt-independent function as an enhancer of procollagen cleavage by the TLD proteinases. SFRP2 binds both procollagen and TLD, thus facilitating the enzymatic reaction by bringing together the proteinase and its substrate.


Pssm-ID: 143555  Cd Length: 128  Bit Score: 112.70  E-value: 1.45e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISM--CQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCL 125
Cdd:cd07446    5 CKPIPANMllCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQKQCHPDTKKFLCSLFAPVCLDDLDEAIQPCRSLCE 84
                         90       100       110
                 ....*....|....*....|....*....|.
gi 119595553 126 SVKRRCEPVLKEFGFAWPESLNCSKFPPQND 156
Cdd:cd07446   85 AVKDGCAPVMSAFGFPWPDMLDCTRFPLDND 115
CRD_FZ3 cd07449
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich ...
48-152 1.61e-29

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 3 (Fz3) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Fz3 plays a vital role in the anterior-posterior guidance of commissural axons. Knockout mice without Fz3 show defects in fiber tracts in the rostral CNS.


Pssm-ID: 143558 [Multi-domain]  Cd Length: 127  Bit Score: 112.79  E-value: 1.61e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIgPCGGMCLSV 127
Cdd:cd07449    5 CEPITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEYGRVTL-PCRRLCQRA 83
                         90       100
                 ....*....|....*....|....*
gi 119595553 128 KRRCEPVLKEFGFAWPESLNCSKFP 152
Cdd:cd07449   84 YSECSKLMEMFGVPWPEDMECSRFP 108
CRD_LIN_17 cd07454
Cysteine-rich domain (CRD) of LIN_17; A cysteine-rich domain (CRD) is an essential component ...
47-163 2.24e-29

Cysteine-rich domain (CRD) of LIN_17; A cysteine-rich domain (CRD) is an essential component of a number of cell surface receptors, which are involved in multiple signal transduction pathways, particularly in modulating the activity of the Wnt proteins, which play a fundamental role in the early development of metazoans. CRD is also found in secreted frizzled related proteins (SFRPs), which lack the transmembrane segment found in the frizzled protein. The CRD domain is also present in the alpha-1 chain of mouse type XVIII collagen, in carboxypeptidase Z, several receptor tyrosine kinases, and the mosaic transmembrane serine protease corin. The CRD domain is well conserved in metazoans - 10 frizzled proteins have been identified in mammals, 4 in Drosophila and 3 in Caenorhabditis elegans. CRD domains have also been identified in multiple tandem copies in a Dictyostelium discoideum protein. Very little is known about the mechanism by which CRD domains interact with their ligands. The domain contains 10 conserved cysteines. The protein lin-17 is involved in cell type specification during Caenorhabditis elegans vulval development.


Pssm-ID: 143563  Cd Length: 124  Bit Score: 112.18  E-value: 2.24e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 126
Cdd:cd07454    4 KCIPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCPIGMPQAVTSCKSVCEQ 83
                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 119595553 127 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCME 163
Cdd:cd07454   84 VKADCFSILEEFGIGWPEPLNCAQFPDPPE---LCMK 117
CRD_SFRP5 cd07444
Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt ...
50-156 3.91e-28

Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related Protein 5 (SFRP5), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs.


Pssm-ID: 143553  Cd Length: 127  Bit Score: 108.88  E-value: 3.91e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  50 PIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKiniPIGPCGGMCLSVKR 129
Cdd:cd07444   11 PADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDR---PIYPCRSLCEAVRD 87
                         90       100
                 ....*....|....*....|....*..
gi 119595553 130 RCEPVLKEFGFAWPESLNCSKFPPQND 156
Cdd:cd07444   88 SCAPVMESYGFPWPEMLHCHKFPLDND 114
CRD_sizzled cd07452
Cysteine-rich domain of the sizzled protein; The cysteine-rich domain (CRD) is an essential ...
47-162 3.18e-26

Cysteine-rich domain of the sizzled protein; The cysteine-rich domain (CRD) is an essential part of the sizzled protein, which regulates bone morphogenetic protein (Bmp) signaling by stabilizing chordin, and plays a critical role in the patterning of vertebrate and invertebrate embryos. Sizzled also functions in the ventral region as a Wnt inhibitor and modulates canonical Wnt signaling. Sizzled proteins belong to the secreted frizzled-related protein family (SFRP), and have be identified in the genomes of birds, fishes and frogs, but not mammals.


Pssm-ID: 143561  Cd Length: 141  Bit Score: 103.81  E-value: 3.18e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPI--RISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKInipIGPCGGMC 124
Cdd:cd07452    8 KCVPIppEMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLDTF---IQPCRSMC 84
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 119595553 125 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCM 162
Cdd:cd07452   85 VAVRDSCAPVLACHGHSWPESLDCDRFPAGED---MCL 119
CRD_crescent cd07453
Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential ...
50-184 3.81e-25

Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential part of the crescent protein, a member of the secreted frizzled-related protein (SFRP) family, which regulates convergent extension movements (CEMs) during gastrulation and neurulation. Xenopus laevis crescent efficiently forms inhibitory complexes with Wnt5a and Wnt11, but this effect is cancelled in the presence of another member of the SFRP family, Frzb1. A potential role for Crescent in head formation is to regulate a non-canonical Wnt pathway positively in the adjacent posterior mesoderm, and negatively in the overlying anterior neuroectoderm.


Pssm-ID: 143562 [Multi-domain]  Cd Length: 135  Bit Score: 100.79  E-value: 3.81e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  50 PIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKiniPIGPCGGMCLSVKR 129
Cdd:cd07453    7 PKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDR---PIYPCRSLCEAVRS 83
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 119595553 130 RCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCMEGPGDEEVPLPHKTPIQPGEEC 184
Cdd:cd07453   84 SCAPLMACYGYPWPEILHCDKFPVDHD---LCISPQFIDTLSPERVKPRASCEDC 135
CRD_SFRP1 cd07443
Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt ...
50-152 4.52e-25

Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt activity; The cysteine-rich domain (CRD) is an essential part of the secreted frizzled-related protein 1 (SFRP1), which regulates the activity of Wnt proteins, key players in a number of fundamental cellular processes such as embryogenesis and postnatal development. SFRPs antagonize the activation of Wnt signaling by binding to the CRDs domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs. SFRP1 is expressed in many tissues and is involved in the regulation of Wnt signaling in osteoblasts, leading to enhanced trabecular bone formation in adults; it has also been shown to control the growth of retinal ganglion cell axons and the elongation of the antero-posterior axis.


Pssm-ID: 143552  Cd Length: 124  Bit Score: 100.36  E-value: 4.52e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  50 PIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKiniPIGPCGGMCLSVKR 129
Cdd:cd07443   11 PADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDR---PVYPCRWLCEAVRD 87
                         90       100
                 ....*....|....*....|...
gi 119595553 130 RCEPVLKEFGFAWPESLNCSKFP 152
Cdd:cd07443   88 SCEPVMQFFGFYWPEMLKCDKFP 110
CRD_FZ6 cd07450
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 6 (Fz6) receptor; The cysteine-rich ...
48-156 5.25e-23

Cysteine-rich Wnt-binding domain (CRD) of the frizzled 6 (Fz6) receptor; The cysteine-rich domain (CRD) is an essential extracellular portion of the frizzled 6 (Fz6) receptor, and is required for binding Wnt proteins, which play fundamental roles in many aspects of early development, such as cell and tissue polarity, neural synapse formation, and the regulation of proliferation. Fz proteins serve as Wnt receptors for multiple signal transduction pathways, including both beta-catenin dependent and -independent cellular signaling, as well as the planar cell polarity pathway and Ca(2+) modulating signaling pathway. CRD containing Fzs have been found in diverse species from amoebas to mammals. 10 different frizzled proteins are found in vertebrata. Frizzled 6 (Fz6) is expressed in the skin and hair follicles and controls hair patterning in mammals using a Fz-dependent tissue polarity system, which is similar to the one that patterns the Drosophila cuticle.


Pssm-ID: 143559 [Multi-domain]  Cd Length: 127  Bit Score: 94.45  E-value: 5.25e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  48 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIpIGPCGGMCLSV 127
Cdd:cd07450    5 CEPITVPRCLKMPYNMTFFPNLMGHYDQDIAAVEMEPFLPLANLRCSPNVHTFLCQAFVPTCTEQIHV-VRPCRELCEKV 83
                         90       100
                 ....*....|....*....|....*....
gi 119595553 128 KRRCEPVLKEFGFAWPESLNCSKFPPQND 156
Cdd:cd07450   84 YSDCKKLIDTFGISWPEELECDRLQYCDE 112
CRD_Carboxypeptidase_Z cd07447
Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The ...
47-151 1.53e-13

Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The cysteine-rich-domain (CRD) is an essential part of carboxypeptidase Z, a member of the carboxypeptidase E family of metallocarboxypeptidases. This is a group of Zn-dependent enzymes implicated in the intra- and extracellular processing of proteins. Carboxypeptidase Z removes C-terminal basic amino acid residues from its substrates, particularly arginine. The CRD acts as a ligand-binding domain for Wnts involved in developmental processes. CPZ binds and may process Wnt-4, CPZ has also been found to enhance the induction of the homeobox gene Cdx1. During vertebrate embryogenesis, the CRD of CPZ upregulates Pax3, a Wnt reporter gene essential for patterning of somites and limb development.


Pssm-ID: 143556  Cd Length: 128  Bit Score: 67.47  E-value: 1.53e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAE-----LQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEkiNIPIGPCG 121
Cdd:cd07447    3 TCTDLLLSYCSDVSYTQTTFPNLLGHRSREVTEagaeyLLLSVLHGLLGGECNPDIRLLGCSVLAPRCEN--DKVIKPCR 80
                         90       100       110
                 ....*....|....*....|....*....|
gi 119595553 122 GMCLSVKRRCEPVLKEFGFAWPESLNCSKF 151
Cdd:cd07447   81 STCEALRKRCSHAFDAIQMAWPYFLDCDRF 110
CRD_corin_1 cd07445
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
45-158 1.34e-11

One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ; The cysteine-rich domain (CRD) is an essential component of corin, a type II transmembrane serine protease which functions as the convertase of the pro-atrial natriuretic peptide (pro-ANP) in the heart. Corin contains two CRDs in its extracellular region, which play an important role in recognition of the physiological substrate, pro-ANP. This model characterizes the first (N-terminal) CRD.


Pssm-ID: 143554  Cd Length: 130  Bit Score: 61.87  E-value: 1.34e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  45 ERRCDPIRISMCQNLGYNVTKMPnLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIG--PCGG 122
Cdd:cd07445    2 TSACMNITHSQCQMLPYHSTLKP-SLLSVKNMEMEKFLKFFSYLHRLSCYQHIMLFGCSLALPECISDGDDRHGllPCRS 80
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 119595553 123 MCLSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHN 158
Cdd:cd07445   81 FCEAAKEGCEPVLGMVNASWPDFLRCSQFRNNTETA 116
CRD_Collagen_XVIII cd07455
Cysteine-rich domain of the variant 3 of collagen XVIII (V3C18 ); The cysteine-rich domain ...
47-156 3.52e-05

Cysteine-rich domain of the variant 3 of collagen XVIII (V3C18 ); The cysteine-rich domain (CRD) is an essential part of the variant 3 of collagen XVIII (V3C18), which regulates major cellular functions such as the differential epithelial morphogenesis of early lung and kidney development. V3C18 is a 170 kD protein, which is proteolotically processed into the CRD-containing 50 kD glucoprotein precursor that binds Wnt3a through its CRD domain and suppresses the Wnt3a-induced stabilization of beta catenin. Full-length V3C18 is unable to inhibit Wnt signaling.


Pssm-ID: 143564  Cd Length: 123  Bit Score: 43.27  E-value: 3.52e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553  47 RCDPI--RISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 124
Cdd:cd07455    4 RCLPVpsSLPFCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPPPPPPCRQFC 83
                         90       100       110
                 ....*....|....*....|....*....|..
gi 119595553 125 LSVKRRCEPVLKEFGFawpeSLNCSKFPPQND 156
Cdd:cd07455   84 EVLQDSCWNLLEGGRL----PVACASLPEQED 111
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
231-442 1.36e-04

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: 43.72  E-value: 1.36e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 231 SLCFISTAFTVLTFLIdSSRFSYPERPIIFLSMCYNIysIAYIVRLTVGreriscdfeeaaepvlIQEGLKNTGCAIIFL 310
Cdd:cd15040   13 GLSLLGLLLTIITYIL-FRKLRKRKPTKILLNLCLAL--LLANLLFLFG----------------INSTDNPVLCTAVAA 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 311 LMYFFGMASSIWWVILTLTWFLAAgLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELTGLCYVGNQNldAL 390
Cdd:cd15040   74 LLHYFLLASFMWMLVEALLLYLRL-VKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYCWLSNGN--GL 150
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 119595553 391 TGFVVAPLftyLVIgtlfIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGV 442
Cdd:cd15040  151 YYAFLGPV---LLI----ILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQL 195
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
93-158 1.72e-04

Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The cysteine-rich domain (CRD) is part of the smoothened receptor (Smo), an integral membrane protein and one of the key players in the Hedgehog (Hh) signaling pathway, critical for development, cell growth and migration, as well as stem cell maintenance. The CRD of Smo is conserved in vertebrates and can also be identified in invertebrates. The precise function of the CRD in Smo is unknown. Mutations in the Drosophila CRD disrupt Smo activity in vivo, while deletion of the CRD in mammalian cells does not seem to affect the activity of overexpressed Smo.


Pssm-ID: 143560  Cd Length: 132  Bit Score: 41.58  E-value: 1.72e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119595553  93 CSSQLQFFLCSVYVPMCtEKINIPIgPCGGMCLSVKRRCEPVLKEFGfaWPESLNCSK--FPPQNDHN 158
Cdd:cd07451   53 CWAVIQPLLCALYMPKC-ENGKVEL-PSQEMCQATRGPCKIVENERG--WPDFLRCDNdrFPPRGCKN 116
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
232-446 5.29e-04

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: 41.81  E-value: 5.29e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 232 LCFISTAF---TVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgreriscdfeeaaepvliQEGLKNTGCAII 308
Cdd:cd13952   11 GCSLSLVGlllTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLL------------------TSSDRPVLCKAL 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 309 FLLMYFFGMASSIWWVILTL-TWFLAAGLKWGHEAIEMhsSYFHIAAWAIPAVKTIVILIMRLVDADELTGL----CYVG 383
Cdd:cd13952   73 AILLHYFLLASFFWMLVEAFdLYRTFVKVFGSSERRRF--LKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYggeyCWLS 150
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119595553 384 NQNldALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVL 446
Cdd:cd13952  151 NGN--ALLWAFYGPVLLILLVNLVFFILTVRILLRKLRETPKQSERKSDRKQLRAYLKLFPLM 211
7tmB2_GPR133-like_Adhesion_V cd15933
orphan GPR133 and related proteins, group V adhesion GPCRs, member of class B2 family of ...
233-464 8.59e-03

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: 38.08  E-value: 8.59e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 233 CFISTAFTVLTFLIDSS-RFSYPERPIIFLSMCYNIYsIAYIVRLTvgreriscdfEEAAEPvliqeglKNTGCAIIFLL 311
Cdd:cd15933   12 CGISIACLALTLIIFLVlRVLSSDRFQIHKNLCVALL-LAQILLLA----------GEWAEG-------NKVACKVVAIL 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 312 MYFFGMASsiwwviltLTWFLAAGL-------KWGHEAIEMHssYFHIAAWAIPAVKTIVILIMRLVDadeltglcYVGN 384
Cdd:cd15933   74 LHFFFMAA--------FSWMLVEGLhlylmivKVFNYKSKMR--YYYFIGWGLPAIIVAISLAILFDD--------YGSP 135
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119595553 385 QN--LDALTGFV---VAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGV-----------FSVLYT 448
Cdd:cd15933  136 NVcwLSLDDGLIwafVGPVIFIITVNTVILILVVKITVSLSTNDAKKSQGTLAQIKSTAKASVvllpilgltwlFGVLVV 215
                        250
                 ....*....|....*.
gi 119595553 449 VPATCVIAcYFYEISN 464
Cdd:cd15933  216 NSQTIVFQ-YIFVILN 230
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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