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Conserved domains on  [gi|22547161|ref|NP_036325|]
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frizzled-4 precursor [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 ...
209-509 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: 571.71  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 209 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 288
Cdd:cd15038   1 GLFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRFKYPERPIIFLSMCYNIYSIAYIVRLLAGRESISCDLDSQT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 289 E-PVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 367
Cdd:cd15038  81 AvSILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWFLAAGLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVMRV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 368 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 447
Cdd:cd15038 161 VDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQLQRDGTKTDKLERLMVRIGIFSVLYTVP 240
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22547161 448 ATCVIACYFYEISNWALFRYS--ADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 509
Cdd:cd15038 241 ATCVIACYFYEYSNRDLWYYGgsAARPNMEVFMLKIFMSLVVGITSGMWIWSAKTLSSWRNFFN 304
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
42-167 8.14e-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: 8.14e-97
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  42 ERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 121
Cdd:cd07448   1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPVPIGPCRPLC 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 22547161 122 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGDEEV 167
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 ...
209-509 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: 571.71  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 209 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 288
Cdd:cd15038   1 GLFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRFKYPERPIIFLSMCYNIYSIAYIVRLLAGRESISCDLDSQT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 289 E-PVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 367
Cdd:cd15038  81 AvSILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWFLAAGLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVMRV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 368 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 447
Cdd:cd15038 161 VDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQLQRDGTKTDKLERLMVRIGIFSVLYTVP 240
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22547161 448 ATCVIACYFYEISNWALFRYS--ADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 509
Cdd:cd15038 241 ATCVIACYFYEYSNRDLWYYGgsAARPNMEVFMLKIFMSLVVGITSGMWIWSAKTLSSWRNFFN 304
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
210-511 1.51e-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: 492.51  E-value: 1.51e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161   210 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFE-EAA 288
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDWSRFRYPERPIIFLSLCYLLVSLGYLIRFVLGREDIACRKDgTGR 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161   289 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 368
Cdd:pfam01534  81 GSYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAAGLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLALGKV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161   369 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTK-TDKLERLMVKIGVFSVLYTVP 447
Cdd:pfam01534 161 DGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLKKDGARaTDKLEKLMVRIGVFSVLYTVP 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161   448 ATCVIACYFYEISN-------WALFRYSADDS----------NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNR 510
Cdd:pfam01534 241 ALIVIACYFYEYANrdswelsWQYINCRAYGIpcldepesrpSFSVFMLKYFMSLVVGITSGFWVWSGKTLESWRRFFRR 320

                  .
gi 22547161   511 L 511
Cdd:pfam01534 321 L 321
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
42-167 8.14e-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: 8.14e-97
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  42 ERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 121
Cdd:cd07448   1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPVPIGPCRPLC 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 22547161 122 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGDEEV 167
Cdd:cd07448  81 LSVKKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGPGDEEV 126
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
45-161 1.97e-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: 1.97e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161     45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINiPIGPCGGMCLSV 124
Cdd:smart00063   1 CEPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDLR-PILPCRSLCEAA 79
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 22547161    125 KRRCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCMEG 161
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 ...
45-151 3.02e-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: 3.02e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161    45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQ-----LTTFTPLIQYGCSSQLQFFLCSVYVPMCT--EKINIPIGPC 117
Cdd:pfam01392   1 CEPITLPMCLGLGYNATVFPNLLGHQTQEEAELSlaylvLSEFEPLVDLSCSPSLRLFLCSLYFPPCTlgPSPKPVCPPC 80
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 22547161   118 GGMCLSVKRRCEPVL--KEFGFAWPESLNCSKFPPQ 151
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 ...
209-509 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: 571.71  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 209 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 288
Cdd:cd15038   1 GLFTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRFKYPERPIIFLSMCYNIYSIAYIVRLLAGRESISCDLDSQT 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 289 E-PVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 367
Cdd:cd15038  81 AvSILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWFLAAGLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVMRV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 368 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 447
Cdd:cd15038 161 VDADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQLQRDGTKTDKLERLMVRIGIFSVLYTVP 240
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22547161 448 ATCVIACYFYEISNWALFRYS--ADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 509
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 ...
209-509 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: 534.96  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 209 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 288
Cdd:cd15909   1 VMFSRSDKNFAEIWMAVWASLCFASTAFTVLTFLIDTSRFRYPERPIIFLSMCYFIYSLGYLIRLFLGRERIACDSLNSG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 289 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 368
Cdd:cd15909  81 VSYLIQEGLESTWCTIVFLLLYYFGMASALWWVILTFTWYLAAGRKWGPEAIEAASSYFHLVAWALPAVKTIVILIMHKV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 369 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 448
Cdd:cd15909 161 DADELTGLCYVGNHDSDALLGFVLVPLAIYLLIGTLFILAGFVSMFRIRRNLKTRGTDTSKLEKLMVKIGVFSVLYTVPA 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 449 TCVIACYFYEISNWALFRYSA-------------------DDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 509
Cdd:cd15909 241 TCVIACYFYEYLNMDQWRIAAieckcqspnaigsdcclqpSIPSVEIYMLKIFMSLVVGITSGMWVWSSKTLQSWQRFIC 320
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
210-511 1.51e-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: 492.51  E-value: 1.51e-173
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161   210 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFE-EAA 288
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDWSRFRYPERPIIFLSLCYLLVSLGYLIRFVLGREDIACRKDgTGR 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161   289 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 368
Cdd:pfam01534  81 GSYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAAGLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLALGKV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161   369 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTK-TDKLERLMVKIGVFSVLYTVP 447
Cdd:pfam01534 161 DGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLKKDGARaTDKLEKLMVRIGVFSVLYTVP 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161   448 ATCVIACYFYEISN-------WALFRYSADDS----------NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNR 510
Cdd:pfam01534 241 ALIVIACYFYEYANrdswelsWQYINCRAYGIpcldepesrpSFSVFMLKYFMSLVVGITSGFWVWSGKTLESWRRFFRR 320

                  .
gi 22547161   511 L 511
Cdd:pfam01534 321 L 321
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
211-505 3.88e-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: 3.88e-158
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 211 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDfEEAAEP 290
Cdd:cd15036   3 WSRGDKDFALVWMAVWSTLCFVSTAFTVLTFLLDPHRFQYPERPIIFLSMCYNVYSVAFLIRAVAGAESIACD-RENGAL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 291 VLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDA 370
Cdd:cd15036  82 YIIQEGLESTGCTLVFLILYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIESHGSYFHMAAWGIPALKTIVILTMRKVAG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 371 DELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATC 450
Cdd:cd15036 162 DELTGLCYVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKVMKTGGTNTEKLEKLMVKIGVFSILYTVPATC 241
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22547161 451 VIACYFYEISNWALFRYSADDS--------------------NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQ 505
Cdd:cd15036 242 VIVCYFYERLNMDYWDLRALEEscrtvpgrrrpdcslphsvpTVAVFMLKIFMSLVVGITSGVWVWSSKTLQTWQ 316
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
209-507 3.97e-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: 447.92  E-value: 3.97e-156
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 209 GLYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA 288
Cdd:cd13951   1 GLFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSRFRYPERPIIFLALCYNFYSLGYLVRLVVGREGIACGKDEGK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 289 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 368
Cdd:cd13951  81 PYLLLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSSEAIEKKSSYFHLVAWGLPAVLTIAVLVLRKV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 369 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 448
Cdd:cd13951 161 DGDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSILSNDGKKTDKLEKLMLRIGIFAVLYTLPA 240
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 22547161 449 TCVIACYFYEISNWALFRYS-------------ADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKC 507
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; ...
210-506 5.50e-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: 427.53  E-value: 5.50e-148
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 210 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISC-DFEEAA 288
Cdd:cd15034   2 FFTEKEREFARLWIGIWSVLCAASTLFTVLTFLIDMDRFRYPERPIIFLSGCYFMVSIAYIVGFFLG-DKVACnGPFPPG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 289 EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 368
Cdd:cd15034  81 GPKTVTQGTKKEGCTILFMMLYFFSMASSIWWVILTLTWFLAAGLKWGHEAIEANSQYFHLAAWAVPAIKTIAILAMGKV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 369 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 448
Cdd:cd15034 161 DGDVLSGVCFVGLSDVDALRGFVLAPLFVYLLIGTSFLLAGFVSLFRIRTVMKHDGTKTDKLEKLMVRIGVFSVLYTVPA 240
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22547161 449 TCVIACYFYEISN---WALFRYSA------------------DDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQK 506
Cdd:cd15034 241 TIVIACYFYEQANresWEKSWLSQnckkyedpcpcpptphplDRPDFTVFMIKYLMTLIVGITSGFWIWSGKTLQSWRQ 319
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
211-507 7.16e-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: 426.69  E-value: 7.16e-148
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 211 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEeaaep 290
Cdd:cd15035   3 FSEDEKTFATFWIGLWSILCFISTLITVLTFLIDMQRFQYPERPIIFLSFCYFMVSVGYIIRLIVGHEAVACDGG----- 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 291 vLIQEGLknTG---CAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 367
Cdd:cd15035  78 -IIRYAT--TGpalCTVVFLLTYFFGMASSIWWVILSLTWFLAAGLKWGNEAISSYSQYFHLVAWLIPAVQTIAILALSA 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 368 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDG-TKTDKLERLMVKIGVFSVLYTV 446
Cdd:cd15035 155 VDGDPISGICYVGNQNLNNLRGFVLAPLVVYLILGTSFLLAGFVSLFRIRNVIKQQGgDKTDKLEKLMIRIGIFSVLYTV 234
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 22547161 447 PATCVIACYFYEISN---WAL-------FRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKC 507
Cdd:cd15035 235 PATIVIACYFYEQHYreiWEKslncpcsPGSIKSRPEYSIFMLKYFMSLVVGITSGFWIWSGKTLDSWKRF 305
7tmF_FZD10 cd15037
class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This ...
211-505 2.65e-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: 2.65e-142
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 211 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDfEEAAEP 290
Cdd:cd15037   3 WSKDDKRFAVVWIAIWSILCFFSSAFTVLTFLIDPQRFKYPERPIIFLSMCYCVYSVGYIIRLFAGAESIACD-RDSGQL 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 291 VLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDA 370
Cdd:cd15037  82 YVIQEGLESTGCTIVFLILYYFGMASSLWWVILTLTWFLAAGKKWGHEAIEANSSYFHLAAWAIPAVKTIMILVMRRVAG 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 371 DELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATC 450
Cdd:cd15037 162 DELTGVCYVGSMDVNALTGFVLIPLACYLIIGTSFILSGFVALFHIRRVMKTGGENTDKLEKLMVRIGVFSVLYTVPATC 241
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22547161 451 VIACYFYEISN---WALF----------RYSADDSNM-----AVE--MLKIFMSLLVGITSGMWIWSAKTLHTWQ 505
Cdd:cd15037 242 VIACYFYERLNmdyWKILatqqkckmdnQTKTLDCVMtssipAVEifMVKIFMLLVVGITSGMWIWTSKTLQSWQ 316
7tmF_FZD5 cd15249
class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This ...
211-506 6.95e-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: 6.95e-127
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 211 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFE----- 285
Cdd:cd15249   3 FSQDERTFATFWIGLWSVLCFISTFTTVATFLIDMERFRYPERPIIFLSACYLFVSLGYIVRLVVGHESVACNREhnhih 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 286 -EAAEPVLiqeglkntgCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILI 364
Cdd:cd15249  83 yETTGPAL---------CTIVFLLIYFFGMASSIWWVILSFTWFLAAGMKWGNEAIAGYSQYFHLAAWLIPSVKSIAVLA 153
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 365 MRLVDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLY 444
Cdd:cd15249 154 LSSVDGDPVAGICYVGNQNLNNLRGFVLAPLVVYLFTGTLFLLAGFVSLFRIRSVIKQGGTKTDKLEKLMIRIGIFTVLY 233
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 22547161 445 TVPATCVIACYFYEI---SNW------------ALFRYSADdsnMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQK 506
Cdd:cd15249 234 TVPATIVVACYVYEQhyrESWeaalncscpgddTQPRARPD---YAVFMLKYFMCLVVGITSGVWIWSGKTLESWRR 307
7tmF_FZD7 cd15246
class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This ...
211-516 9.50e-126

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: 371.27  E-value: 9.50e-126
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 211 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgRERISC--DFEEAA 288
Cdd:cd15246   3 FKEEEVRFARLWVGIWSILCCASTLFTVLTYLVDMRRFSYPERPIIFLSGCYFMVAVAYAAGFLL-EDRVVCveRFSDDG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 289 EPVLIQeGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 368
Cdd:cd15246  82 YRTVAQ-GTKKEGCTILFMVLYFFGMASSIWWVILSLTWFLSAGMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMGQV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 369 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 448
Cdd:cd15246 161 DGDLLSGVCYVGIYSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIGVFSVLYTVPA 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 449 TCVIACYFYEIS-------NWAL------------FRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSN 509
Cdd:cd15246 241 TIVLACYFYEQAfretwekTWLLqtckryavpcpnNNFAPMSPDFTVFMIKYLMTMIVGITSGFWIWSGKTLQSWRRFYH 320

                ....*..
gi 22547161 510 RLVNSGK 516
Cdd:cd15246 321 RLSNGSK 327
7tmF_FZD8 cd15250
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This ...
211-505 1.39e-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: 367.72  E-value: 1.39e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 211 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAAEP 290
Cdd:cd15250   3 FSQEERTFTAFWIGLWSVLCFLSTFATVSTFLIDMERFKYPERPIIFLSACYLFVSLGYLVRLIAGHEKVACSRGALAEV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 291 VLIQegLKNTG---CAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 367
Cdd:cd15250  83 EHIH--YETTGpalCTVVFLLIYFFGMASSIWWVILSLTWFLAAGMKWGNEAIAGYSQYFHLAAWLIPSVKSIAVLALSS 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 368 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 447
Cdd:cd15250 161 VDGDPVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVSLFRIRSVIKQGGTKTDKLEKLMIRIGIFTVLYTVP 240
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 448 ATCVIACYFYEISN---WAL---------FRYSADDSNMAVEMLKIFMSLLVGITSGMWIWSAKTLHTWQ 505
Cdd:cd15250 241 ATIVVACYFYEQHNrqrWEIthncnclrdQPDQARRPDYAVFMLKYFMCLVVGITSGVWTWSGKTLESWR 310
7tmF_FZD2 cd15245
class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This ...
210-516 3.05e-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: 367.42  E-value: 3.05e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 210 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISCD--FEEA 287
Cdd:cd15245   2 FFSQDEIRFARIWILIWSVLCCASTFFTVTTYLVDMQRFRYPERPIIFLSGCYTMVSVAYIAGFVLG-DKVVCNerFSED 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 288 AEPVLIQeGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRL 367
Cdd:cd15245  81 GYKTVVQ-GTKKEGCTILFMMLYFFSMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMGQ 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 368 VDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVP 447
Cdd:cd15245 160 IDGDLLSGVCFVGLNNIDPLRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLERLMVRIGVFSVLYTVP 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 448 ATCVIACYFYEIS---NWALFRYSADDSNMA----------------VEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCS 508
Cdd:cd15245 240 ATIVIACYFYEQAfrqHWERSWISQNCKSLAipcplqytprmtpdftVYMIKYLMTLIVGITSGFWIWSGKTLHSWRKFY 319

                ....*...
gi 22547161 509 NRLVNSGK 516
Cdd:cd15245 320 TRLTNSRQ 327
7tmF_FZD1_insect cd15248
class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
211-511 7.74e-119

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: 7.74e-119
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 211 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISC-------- 282
Cdd:cd15248   3 FPERERTFSRYWIGSWAAVCMASCLFTVLTFLIDSSRFRYPERPIVFLSVCYLMVAAAYVAGLGAG-DSVSCnepfpppv 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 283 DFEEAAEPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVI 362
Cdd:cd15248  82 KLGRLQMVSTITQGTKTESCTVLFMVLYFFSMAASIWWVVLTLTWFLAAGLKWGHEAIEAKSHYFHLVAWAVPALKTISI 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 363 LIMRLVDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSV 442
Cdd:cd15248 162 LAMGKVEGDVLSGVCYVGLWDMHALRGFVLAPLCVYLSLGTIFLLAGFISLFRIRTVMKHDGTKTDKLEKLMLRIGIFSF 241
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 443 LYTVPATCVIACYFYEISN---WAL---------FRYSA----------DDSNMAVEMLKIFMSLLVGITSGMWIWSAKT 500
Cdd:cd15248 242 LYTLPALIVLACLFYEQAHfdsWMLqwhrdickpPSWSIpacratgspeARPEFQVFMIKYLMSMIVGITSSVWIWSSKT 321
                       330
                ....*....|.
gi 22547161 501 LHTWQKCSNRL 511
Cdd:cd15248 322 LVSWRNFYERL 332
7tmF_FZD1 cd15247
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
217-514 1.06e-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: 1.06e-118
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 217 EFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgRERISCD--FEEAAEPVLIQ 294
Cdd:cd15247  19 RFARIWIGIWSVLCCASTLFTVLTYLVDMKRFSYPERPIIFLSGCYTMVAIAYIAGFLL-EDKVVCNdkFAEDGIKTVAQ 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 295 eGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELT 374
Cdd:cd15247  98 -GTKKEGCTILFMMLYFFSMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAIKTITILAVGQVDGDVLS 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 375 GLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVIAC 454
Cdd:cd15247 177 GVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIGIFSVLYTVPATIVIAC 256
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22547161 455 YFYE---------------ISNWALFRYSADDSNMA----VEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCSNRLVNS 514
Cdd:cd15247 257 YFYEqafreqwerswisqsCKTYAIPCPAHSHPPMSpdftVFMIKYLMTLIVGITSGFWIWSGKTLNSWRKFYTRLTNS 335
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
42-167 8.14e-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: 8.14e-97
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  42 ERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 121
Cdd:cd07448   1 DRRCEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPVPIGPCRPLC 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 22547161 122 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGDEEV 167
Cdd:cd07448  81 LSVKKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGPGDEEV 126
7tmF_FZD3_FZD6-like cd15910
class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G ...
217-504 1.24e-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: 1.24e-80
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 217 EFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISCDFEEAAEPV--LIQ 294
Cdd:cd15910   9 MFARYFIGVVSILCLLATLFTFLTFLIDVNRFRYPERPIIFYAVCYFVVSLIFFVGFLLG-DDVACNHAIMDENNgaTVV 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 295 EGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELT 374
Cdd:cd15910  88 EGSRNKACTILFMILYFFTMAGTVWWVILTITWFLAAGFKWGSEAIEKKALYFHALAWGIPGVLTMVLLATNKIEGDNIS 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 375 GLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVIAC 454
Cdd:cd15910 168 GVCFVGLYDSDGLRFFVLLPLCLYVLVGMSLLLAGIICLNRVRKSIHDDETNQEKLAKFMIRIGVFSILYLVPLLTLIGC 247
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22547161 455 YFYEISN-------WALFR---------YSADDS---NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTW 504
Cdd:cd15910 248 YAYEQSNrkswestWVVRNcrryhipcpQLAQGNprpGLFLFCIKYLMTLIVGIPPVFWVGSKKTCAEW 316
7tmF_FZD3 cd15033
class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This ...
211-504 2.37e-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: 249.09  E-value: 2.37e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 211 YSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgRERISCDFEEAAE- 289
Cdd:cd15033   3 FRREELSFARYFIGVISIVCLSATLFTFLTFLIDVTRFRYPERPIIFYAVCYMMVSLIFFIGFLL-EDRVACNAASPGQy 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 290 -PVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLV 368
Cdd:cd15033  82 kASTVTQGSHNKACTMLFMVLYFFTMAGSVWWVILTITWFLAAVPKWGSEAIEKKALLFHASAWGIPGTLTIILLAMNKI 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 369 DADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPA 448
Cdd:cd15033 162 EGDNISGVCFVGLYDVDALRYFVLAPLCLDVVVGVSLLLAGIISLNRVRIEIPLEKENQDKLVKFMIRIGVFSVLYLVPL 241
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 22547161 449 TCVIACYFYEIS-------NWALFR---------YSADDS---NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTW 504
Cdd:cd15033 242 LVVIGCYFYEQAyrgvwetTWVQERcreyhipcpYKVTQTsrpDLILFLMKYLMALVVGIPSVFWVGSKKTCFEW 316
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
217-504 1.60e-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: 233.97  E-value: 1.60e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 217 EFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGrERISCDFE----EAAEPVL 292
Cdd:cd15032   9 DFAKSFIGIVSIFCLCATLFTFLTFLIDVKRFRYPERPIIYYSVCYSIVSLMYFIGFLLG-NSTACNKAdeklELGDTVV 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 293 IqeGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADE 372
Cdd:cd15032  88 L--GSQNKACTVLFMLLYFFTMAGTIWWVILTITWFLAAGRKWSCEAIEQKALWFHAVAWGIPGFLTIMLLAMNKVEGDN 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 373 LTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVLYTVPATCVI 452
Cdd:cd15032 166 ISGVCFVGLYDLDASRYFVLLPLCLCVFVGLSLLLAGIISLNHVRQVIQHDGRNQEKLKKFMIRIGVFSGLYLVPLVTLL 245
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 22547161 453 ACYFYEISN---WA---LFRYSADDS-------------NMAVEMLKIFMSLLVGITSGMWIWSAKTLHTW 504
Cdd:cd15032 246 GCYVYEQVYrrtWEitwVSDHCQQYHipcpyqakavarpELALFLIKYLMTLIVGISAVFWVGSKKTCSEW 316
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
221-506 3.79e-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: 3.79e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 221 IWMAVWASLCFISTAFTVLTFLID---SSRfsYPERPIIFLSMCYNIYSIAYIVRLTVG-RERISC---DFEEAAEPvli 293
Cdd:cd15030  13 KFIAVFASVCLLCTLFTVLTFFIDwknSNR--YPAVILFYINACFFIGSIGWLAQFLPGaREDIVCrkdGTMRLGEP--- 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 294 QEGlKNTGCAIIFLLMYFFGMASSIWWVILTLTW---FLAAGLKwgHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDA 370
Cdd:cd15030  88 SAG-ENLSCVVIFVLVYYFLMAGCVWFVILTYAWhmsFKALGTI--QDRLDKKTAYFHLIAWSLPLVLTITIMALGQVDG 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 371 DELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSN---LQKDGTKTdKLERLMVKIGVFSVLYTVP 447
Cdd:cd15030 165 DSVSGICFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKLKISspeILSEKASS-KIRETIVRLGIFAFLALGF 243
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 448 ATCVIACYFYEISN---WAL-FR-------------YSADDS---------NMAVEMLKIFMSLLVGITSGMWIWSAKTL 501
Cdd:cd15030 244 VLITFACHVYEFFNqaeWEKsFRdyivceanvtiaeQTNGDIpecelksrpSLAMLQLHLLALFGAGIAMSSWVWTRATL 323

                ....*
gi 22547161 502 HTWQK 506
Cdd:cd15030 324 ETWKR 328
7tmF_FZD3_insect cd15031
class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; ...
210-508 4.15e-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: 195.76  E-value: 4.15e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 210 LYSRSAKEFTDIWMAVWASLCFISTAFTVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAA- 288
Cdd:cd15031   2 FYTTRQKKLVESWMLVLSAVSFILTLFALVTFWAEPTRFGYPERPVLFMALCYNLISLCYLERGILGTFTNCSARSLAId 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 289 --EPVLIQEGLKNTGCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMR 366
Cdd:cd15031  82 cdDRYLRQDCLLTPQCLASFIITYYLSLSAASWWLIFALCWYLSSAKKWSSEALEKKSGLFHVLAWVPPLAPPIAALLLE 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 367 LVDADELTGLCYVGNQNLDALTGFvvaPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKleRLMVKIGVFSVLYTV 446
Cdd:cd15031 162 RVSASELTGTCTASGFVESSISEL---PALILLLLGLYLTIAALRSLLSLQQQLQSRLAHAPQ--RILARVSIFSLLYLI 236
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 22547161 447 PATCVIACYFYEISNWALFRYSADDSNMA------------VEMLKIFMSLLVGITSGMWIWSAKTLHTWQKCS 508
Cdd:cd15031 237 PAAAALICKLCERWLQPVPECNALQEDCAppatdneflsalPALLRVFFFLIGGTATGLWLWSRKSCESWRSRL 310
CRD_FZ9_like cd07457
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich ...
44-162 3.36e-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: 3.36e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 123
Cdd:cd07457   2 KCERITIPMCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQVSIPIPACRSMCEQ 81
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 22547161 124 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGP 162
Cdd:cd07457  82 ARDKCSPIMEQFSFSWPDSLDCDRLPRKNDPKDLCMEAP 120
CRD_FZ10 cd07462
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 10 (Fz10) receptor; The cysteine-rich ...
42-164 3.57e-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: 3.57e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  42 ERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 121
Cdd:cd07462   2 EGRCQPIEIPMCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQVSTPIPACRVMC 81
                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 22547161 122 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGD 164
Cdd:cd07462  82 EQARLKCSPIMEQFNFKWPDSLDCSKLPNKNDPNYLCMEAPNN 124
CRD_FZ9 cd07463
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich ...
44-162 4.21e-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: 4.21e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 123
Cdd:cd07463   4 KCQPVVIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQVSTSIPACRPMCEQ 83
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 22547161 124 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGP 162
Cdd:cd07463  84 ARQKCSPIMEQFNFGWPESLDCSRLPTRNDPNALCMEAP 122
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
45-161 1.97e-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: 1.97e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161     45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINiPIGPCGGMCLSV 124
Cdd:smart00063   1 CEPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDLR-PILPCRSLCEAA 79
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 22547161    125 KRRCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCMEG 161
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 ...
43-160 2.28e-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: 155.26  E-value: 2.28e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  43 RRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTeKINIPIGPCGGMCL 122
Cdd:cd07458   1 GKCEPITIPLCTDIPYNMTIFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCT-VLERPIPPCRSLCE 79
                        90       100       110
                ....*....|....*....|....*....|....*...
gi 22547161 123 SVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNhMCME 160
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 ...
44-163 2.34e-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: 2.34e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 123
Cdd:cd07066   1 KCEPIPLPLCRGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTPDGDRPIPPCRSLCEE 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 22547161 124 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDhNHMCMEGPG 163
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 ...
44-163 1.27e-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: 1.27e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 123
Cdd:cd07456   1 KCEEITIPMCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYDKPLPPCRSVCER 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 22547161 124 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPG 163
Cdd:cd07456  81 ARDGCAPIMRQYGFAWPERMSCDALPEGGDPDNLCMDRNN 120
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
45-151 3.02e-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: 3.02e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161    45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQ-----LTTFTPLIQYGCSSQLQFFLCSVYVPMCT--EKINIPIGPC 117
Cdd:pfam01392   1 CEPITLPMCLGLGYNATVFPNLLGHQTQEEAELSlaylvLSEFEPLVDLSCSPSLRLFLCSLYFPPCTlgPSPKPVCPPC 80
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 22547161   118 GGMCLSVKRRCEPVL--KEFGFAWPESLNCSKFPPQ 151
Cdd:pfam01392  81 RSLCEEVRYGCEPLLeeAKFGFSWPEFLDCDSLPAD 116
CRD_FZ8 cd07461
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich ...
41-160 7.92e-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: 7.92e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  41 EERRCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGM 120
Cdd:cd07461   1 KELQCQEITVPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYKKPLPPCRSV 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 22547161 121 CLSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCME 160
Cdd:cd07461  81 CERAKAGCAPLMRQYGFPWPDRMRCDLLPEQGNPDTLCMD 120
CRD_FZ5 cd07460
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 5 (Fz5) receptor.proteins; The ...
45-160 3.26e-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: 3.26e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLSV 124
Cdd:cd07460   5 CQEITVPMCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPDYRKPLPPCRSVCERA 84
                        90       100       110
                ....*....|....*....|....*....|....*.
gi 22547161 125 KRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCME 160
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 ...
44-159 8.80e-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: 8.80e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAEL--QLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 121
Cdd:cd07888   1 QCEPITLELCMNLPYNTTRYPNYLGHRTQKEASIswESSLFPALVQTNCYKYLMFFACTILVPKCDPVTQQRIPPCRSLC 80
                        90       100       110
                ....*....|....*....|....*....|....*...
gi 22547161 122 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCM 159
Cdd:cd07888  81 RNSKERCESVLGIVGLQWPEDTDCAQFPEENSDNQTCL 118
CRD_FZ2 cd07464
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich ...
45-149 2.82e-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: 2.82e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTeKINIPIGPCGGMCLSV 124
Cdd:cd07464   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSLELRFFLCSMYAPVCT-VLEQAIPPCRSICERA 83
                        90       100
                ....*....|....*....|....*
gi 22547161 125 KRRCEPVLKEFGFAWPESLNCSKFP 149
Cdd:cd07464  84 RQGCEALMNKFGFQWPERLRCENFP 108
CRD_FZ1 cd07465
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich ...
45-149 3.42e-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: 3.42e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTeKINIPIGPCGGMCLSV 124
Cdd:cd07465   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVCT-VLEQALPPCRSLCERA 83
                        90       100
                ....*....|....*....|....*
gi 22547161 125 KRRCEPVLKEFGFAWPESLNCSKFP 149
Cdd:cd07465  84 RQGCEALMNKFGFQWPDTLRCEKFP 108
CRD_FZ7 cd07466
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich ...
45-149 4.01e-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: 4.01e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTeKINIPIGPCGGMCLSV 124
Cdd:cd07466   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELKFFLCSMYAPVCT-VLEQAIPPCRSLCERA 83
                        90       100
                ....*....|....*....|....*
gi 22547161 125 KRRCEPVLKEFGFAWPESLNCSKFP 149
Cdd:cd07466  84 RQGCEALMNKFGFQWPERLRCENFP 108
CRD_SFRP3 cd07441
Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt ...
45-149 7.30e-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: 7.30e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKI-NIPIGPCGGMCLS 123
Cdd:cd07441   4 CEPVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTIDFqHEPIKPCKSVCER 83
                        90       100
                ....*....|....*....|....*.
gi 22547161 124 VKRRCEPVLKEFGFAWPESLNCSKFP 149
Cdd:cd07441  84 ARAGCEPVLIRYRHTWPESLACEELP 109
CRD_SFRP4 cd07442
Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The ...
45-149 8.12e-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: 8.12e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCT-EKINIPIGPCGGMCLS 123
Cdd:cd07442   5 CEAVRIPMCRHMPWNITRMPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICTlEFLYDPIKPCRSVCQR 84
                        90       100
                ....*....|....*....|....*.
gi 22547161 124 VKRRCEPVLKEFGFAWPESLNCSKFP 149
Cdd:cd07442  85 ARDGCEPIMRRYNHSWPESLACDDLP 110
CRD_FZ3 cd07449
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich ...
45-149 1.37e-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: 1.37e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIgPCGGMCLSV 124
Cdd:cd07449   5 CEPITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEYGRVTL-PCRRLCQRA 83
                        90       100
                ....*....|....*....|....*
gi 22547161 125 KRRCEPVLKEFGFAWPESLNCSKFP 149
Cdd:cd07449  84 YSECSKLMEMFGVPWPEDMECSRFP 108
CRD_SFRP2 cd07446
Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt ...
45-153 1.41e-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: 1.41e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISM--CQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCL 122
Cdd:cd07446   5 CKPIPANMllCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQKQCHPDTKKFLCSLFAPVCLDDLDEAIQPCRSLCE 84
                        90       100       110
                ....*....|....*....|....*....|.
gi 22547161 123 SVKRRCEPVLKEFGFAWPESLNCSKFPPQND 153
Cdd:cd07446  85 AVKDGCAPVMSAFGFPWPDMLDCTRFPLDND 115
CRD_LIN_17 cd07454
Cysteine-rich domain (CRD) of LIN_17; A cysteine-rich domain (CRD) is an essential component ...
44-160 2.31e-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: 2.31e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMCLS 123
Cdd:cd07454   4 KCIPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCPIGMPQAVTSCKSVCEQ 83
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 22547161 124 VKRRCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCME 160
Cdd:cd07454  84 VKADCFSILEEFGIGWPEPLNCAQFPDPPE---LCMK 117
CRD_SFRP5 cd07444
Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt ...
47-153 3.84e-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: 3.84e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  47 PIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKiniPIGPCGGMCLSVKR 126
Cdd:cd07444  11 PADLPLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDR---PIYPCRSLCEAVRD 87
                        90       100
                ....*....|....*....|....*..
gi 22547161 127 RCEPVLKEFGFAWPESLNCSKFPPQND 153
Cdd:cd07444  88 SCAPVMESYGFPWPEMLHCHKFPLDND 114
CRD_sizzled cd07452
Cysteine-rich domain of the sizzled protein; The cysteine-rich domain (CRD) is an essential ...
44-159 3.14e-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: 3.14e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPI--RISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKInipIGPCGGMC 121
Cdd:cd07452   8 KCVPIppEMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLDTF---IQPCRSMC 84
                        90       100       110
                ....*....|....*....|....*....|....*...
gi 22547161 122 LSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCM 159
Cdd:cd07452  85 VAVRDSCAPVLACHGHSWPESLDCDRFPAGED---MCL 119
CRD_crescent cd07453
Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential ...
47-181 3.76e-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: 3.76e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  47 PIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKiniPIGPCGGMCLSVKR 126
Cdd:cd07453   7 PKSMALCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDR---PIYPCRSLCEAVRS 83
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 22547161 127 RCEPVLKEFGFAWPESLNCSKFPPQNDhnhMCMEGPGDEEVPLPHKTPIQPGEEC 181
Cdd:cd07453  84 SCAPLMACYGYPWPEILHCDKFPVDHD---LCISPQFIDTLSPERVKPRASCEDC 135
CRD_SFRP1 cd07443
Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt ...
47-149 4.46e-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: 4.46e-25
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  47 PIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKiniPIGPCGGMCLSVKR 126
Cdd:cd07443  11 PADLRLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDR---PVYPCRWLCEAVRD 87
                        90       100
                ....*....|....*....|...
gi 22547161 127 RCEPVLKEFGFAWPESLNCSKFP 149
Cdd:cd07443  88 SCEPVMQFFGFYWPEMLKCDKFP 110
CRD_FZ6 cd07450
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 6 (Fz6) receptor; The cysteine-rich ...
45-153 5.20e-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: 5.20e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  45 CDPIRISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIpIGPCGGMCLSV 124
Cdd:cd07450   5 CEPITVPRCLKMPYNMTFFPNLMGHYDQDIAAVEMEPFLPLANLRCSPNVHTFLCQAFVPTCTEQIHV-VRPCRELCEKV 83
                        90       100
                ....*....|....*....|....*....
gi 22547161 125 KRRCEPVLKEFGFAWPESLNCSKFPPQND 153
Cdd:cd07450  84 YSDCKKLIDTFGISWPEELECDRLQYCDE 112
CRD_Carboxypeptidase_Z cd07447
Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The ...
44-148 1.50e-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: 1.50e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPIRISMCQNLGYNVTKMPNLVGHELQTDAE-----LQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEkiNIPIGPCG 118
Cdd:cd07447   3 TCTDLLLSYCSDVSYTQTTFPNLLGHRSREVTEagaeyLLLSVLHGLLGGECNPDIRLLGCSVLAPRCEN--DKVIKPCR 80
                        90       100       110
                ....*....|....*....|....*....|
gi 22547161 119 GMCLSVKRRCEPVLKEFGFAWPESLNCSKF 148
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 ...
42-155 1.37e-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: 1.37e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  42 ERRCDPIRISMCQNLGYNVTKMPnLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIG--PCGG 119
Cdd:cd07445   2 TSACMNITHSQCQMLPYHSTLKP-SLLSVKNMEMEKFLKFFSYLHRLSCYQHIMLFGCSLALPECISDGDDRHGllPCRS 80
                        90       100       110
                ....*....|....*....|....*....|....*.
gi 22547161 120 MCLSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHN 155
Cdd:cd07445  81 FCEAAKEGCEPVLGMVNASWPDFLRCSQFRNNTETA 116
CRD_Collagen_XVIII cd07455
Cysteine-rich domain of the variant 3 of collagen XVIII (V3C18 ); The cysteine-rich domain ...
44-153 3.78e-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: 3.78e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161  44 RCDPI--RISMCQNLGYNVTKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGMC 121
Cdd:cd07455   4 RCLPVpsSLPFCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPPPPPPCRQFC 83
                        90       100       110
                ....*....|....*....|....*....|..
gi 22547161 122 LSVKRRCEPVLKEFGFawpeSLNCSKFPPQND 153
Cdd:cd07455  84 EVLQDSCWNLLEGGRL----PVACASLPEQED 111
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
228-439 1.19e-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: 1.19e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 228 SLCFISTAFTVLTFLIdSSRFSYPERPIIFLSMCYNIysIAYIVRLTVGreriscdfeeaaepvlIQEGLKNTGCAIIFL 307
Cdd:cd15040  13 GLSLLGLLLTIITYIL-FRKLRKRKPTKILLNLCLAL--LLANLLFLFG----------------INSTDNPVLCTAVAA 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 308 LMYFFGMASSIWWVILTLTWFLAAgLKWGHEAIEMHSSYFHIAAWAIPAVKTIVILIMRLVDADELTGLCYVGNQNldAL 387
Cdd:cd15040  74 LLHYFLLASFMWMLVEALLLYLRL-VKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSSGYCWLSNGN--GL 150
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 22547161 388 TGFVVAPLftyLVIgtlfIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGV 439
Cdd:cd15040 151 YYAFLGPV---LLI----ILVNLVIFVLVLRKLLRLSAKRNKKKRKKTKAQL 195
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
90-155 1.73e-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: 1.73e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 22547161  90 CSSQLQFFLCSVYVPMCtEKINIPIgPCGGMCLSVKRRCEPVLKEFGfaWPESLNCSK--FPPQNDHN 155
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 ...
229-443 4.89e-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: 42.20  E-value: 4.89e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 229 LCFISTAF---TVLTFLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVgreriscdfeeaaepvliQEGLKNTGCAII 305
Cdd:cd13952  11 GCSLSLVGlllTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIGQLL------------------TSSDRPVLCKAL 72
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 306 FLLMYFFGMASSIWWVILTL-TWFLAAGLKWGHEAIEMhsSYFHIAAWAIPAVKTIVILIMRLVDADELTGL----CYVG 380
Cdd:cd13952  73 AILLHYFLLASFFWMLVEAFdLYRTFVKVFGSSERRRF--LKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYggeyCWLS 150
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 22547161 381 NQNldALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGVFSVL 443
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 ...
230-461 7.73e-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: 38.46  E-value: 7.73e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 230 CFISTAFTVLTFLIDSS-RFSYPERPIIFLSMCYNIYsIAYIVRLTvgreriscdfEEAAEPvliqeglKNTGCAIIFLL 308
Cdd:cd15933  12 CGISIACLALTLIIFLVlRVLSSDRFQIHKNLCVALL-LAQILLLA----------GEWAEG-------NKVACKVVAIL 73
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 309 MYFFGMASsiwwviltLTWFLAAGL-------KWGHEAIEMHssYFHIAAWAIPAVKTIVILIMRLVDadeltglcYVGN 381
Cdd:cd15933  74 LHFFFMAA--------FSWMLVEGLhlylmivKVFNYKSKMR--YYYFIGWGLPAIIVAISLAILFDD--------YGSP 135
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22547161 382 QN--LDALTGFV---VAPLFTYLVIGTLFIAAGLVALFKIRSNLQKDGTKTDKLERLMVKIGV-----------FSVLYT 445
Cdd:cd15933 136 NVcwLSLDDGLIwafVGPVIFIITVNTVILILVVKITVSLSTNDAKKSQGTLAQIKSTAKASVvllpilgltwlFGVLVV 215
                       250
                ....*....|....*.
gi 22547161 446 VPATCVIAcYFYEISN 461
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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