NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|4503835|ref|NP_003499|]
View 

frizzled-9 precursor [Homo sapiens]

Protein Classification

CRD_FZ and 7tmF_FZD9 domain-containing protein( domain architecture ID 11635489)

CRD_FZ and 7tmF_FZD9 domain-containing protein

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
221-542 0e+00

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: 668.97  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGA 300
Cdd:cd15036   1 VYWSRGDKDFALVWMAVWSTLCFVSTAFTVLTFLLDPHRFQYPERPIIFLSMCYNVYSVAFLIRAVAGAESIACDRENGA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVA 380
Cdd:cd15036  81 LYIIQEGLESTGCTLVFLILYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIESHGSYFHMAAWGIPALKTIVILTMRKVA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  381 GDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 460
Cdd:cd15036 161 GDELTGLCYVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKVMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  461 CVIVCYVYERLNMDFWRLRATEQPCAAAAGpGGRRDCSLPgGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSL 540
Cdd:cd15036 241 CVIVCYFYERLNMDYWDLRALEESCRTVPG-RRRPDCSLP-HSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTLQTWQGL 318

                ..
gi 4503835  541 CY 542
Cdd:cd15036 319 CC 320
CRD_FZ super family cl02447
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
35-161 1.15e-88

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.


The actual alignment was detected with superfamily member cd07463:

Pssm-ID: 470581  Cd Length: 127  Bit Score: 269.97  E-value: 1.15e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   35 GAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPM 114
Cdd:cd07463   1 RAAKCQPVVIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQVSTSIPACRPM 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4503835  115 CEQARLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAPENATA 161
Cdd:cd07463  81 CEQARQKCSPIMEQFNFGWPESLDCSRLPTRNDPNALCMEAPENATA 127
 
Name Accession Description Interval E-value
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
221-542 0e+00

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: 668.97  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGA 300
Cdd:cd15036   1 VYWSRGDKDFALVWMAVWSTLCFVSTAFTVLTFLLDPHRFQYPERPIIFLSMCYNVYSVAFLIRAVAGAESIACDRENGA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVA 380
Cdd:cd15036  81 LYIIQEGLESTGCTLVFLILYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIESHGSYFHMAAWGIPALKTIVILTMRKVA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  381 GDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 460
Cdd:cd15036 161 GDELTGLCYVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKVMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  461 CVIVCYVYERLNMDFWRLRATEQPCAAAAGpGGRRDCSLPgGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSL 540
Cdd:cd15036 241 CVIVCYFYERLNMDYWDLRALEESCRTVPG-RRRPDCSLP-HSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTLQTWQGL 318

                ..
gi 4503835  541 CY 542
Cdd:cd15036 319 CC 320
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
222-544 2.29e-177

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: 504.06  E-value: 2.29e-177
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835    222 FWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVAC--DQEAG 299
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDWSRFRYPERPIIFLSLCYLLVSLGYLIRFVLGREDIACrkDGTGR 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835    300 ALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKV 379
Cdd:pfam01534  81 GSYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAAGLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLALGKV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835    380 AGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKT-GGTNTEKLEKLMVKIGVFSILYTVP 458
Cdd:pfam01534 161 DGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLKKdGARATDKLEKLMVRIGVFSVLYTVP 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835    459 ATCVIVCYVYERLNMDFWRLRATEQPCAAAAGPggrrdCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQ 538
Cdd:pfam01534 241 ALIVIACYFYEYANRDSWELSWQYINCRAYGIP-----CLDEPESRPSFSVFMLKYFMSLVVGITSGFWVWSGKTLESWR 315

                  ....*.
gi 4503835    539 SLCYRK 544
Cdd:pfam01534 316 RFFRRL 321
CRD_FZ9 cd07463
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich ...
35-161 1.15e-88

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: 269.97  E-value: 1.15e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   35 GAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPM 114
Cdd:cd07463   1 RAAKCQPVVIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQVSTSIPACRPM 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4503835  115 CEQARLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAPENATA 161
Cdd:cd07463  81 CEQARQKCSPIMEQFNFGWPESLDCSRLPTRNDPNALCMEAPENATA 127
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
39-155 2.52e-48

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: 164.02  E-value: 2.52e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835      39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVStPIPACRPMCEQA 118
Cdd:smart00063   1 CEPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDLR-PILPCRSLCEAA 79
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 4503835     119 RLRCAPIMEQFNFGWPDSLDCARLPTRNDphaLCMEA 155
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 ...
39-143 6.03e-35

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: 127.68  E-value: 6.03e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835     39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQ-----GEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCT--DQVSTPIPAC 111
Cdd:pfam01392   1 CEPITLPMCLGLGYNATVFPNLLGHQTQeeaelSLAYLVLSEFEPLVDLSCSPSLRLFLCSLYFPPCTlgPSPKPVCPPC 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 4503835    112 RPMCEQARLRCAPIME--QFNFGWPDSLDCARLP 143
Cdd:pfam01392  81 RSLCEEVRYGCEPLLEeaKFGFSWPEFLDCDSLP 114
 
Name Accession Description Interval E-value
7tmF_FZD9 cd15036
class F frizzled subfamily 9, member of 7-transmembrane G protein-coupled receptors; This ...
221-542 0e+00

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: 668.97  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGA 300
Cdd:cd15036   1 VYWSRGDKDFALVWMAVWSTLCFVSTAFTVLTFLLDPHRFQYPERPIIFLSMCYNVYSVAFLIRAVAGAESIACDRENGA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVA 380
Cdd:cd15036  81 LYIIQEGLESTGCTLVFLILYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIESHGSYFHMAAWGIPALKTIVILTMRKVA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  381 GDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 460
Cdd:cd15036 161 GDELTGLCYVGSMDVSALTGFVLVPLSCYLVTGTSFLLTGFVALFHIRKVMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  461 CVIVCYVYERLNMDFWRLRATEQPCAAAAGpGGRRDCSLPgGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSL 540
Cdd:cd15036 241 CVIVCYFYERLNMDYWDLRALEESCRTVPG-RRRPDCSLP-HSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTLQTWQGL 318

                ..
gi 4503835  541 CY 542
Cdd:cd15036 319 CC 320
7tmF_FZD4_9_10-like cd15909
class F frizzled subfamilies 4, 9, 10, and related proteins; member of 7-transmembrane G ...
221-541 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: 546.13  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQ-EAG 299
Cdd:cd15909   1 VMFSRSDKNFAEIWMAVWASLCFASTAFTVLTFLIDTSRFRYPERPIIFLSMCYFIYSLGYLIRLFLGRERIACDSlNSG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  300 ALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKV 379
Cdd:cd15909  81 VSYLIQEGLESTWCTIVFLLLYYFGMASALWWVILTFTWYLAAGRKWGPEAIEAASSYFHLVAWALPAVKTIVILIMHKV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  380 AGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPA 459
Cdd:cd15909 161 DADELTGLCYVGNHDSDALLGFVLVPLAIYLLIGTLFILAGFVSMFRIRRNLKTRGTDTSKLEKLMVKIGVFSVLYTVPA 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  460 TCVIVCYVYERLNMDFWRLRATEQPCaaAAGPGGRRDCSLPgGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQS 539
Cdd:cd15909 241 TCVIACYFYEYLNMDQWRIAAIECKC--QSPNAIGSDCCLQ-PSIPSVEIYMLKIFMSLVVGITSGMWVWSSKTLQSWQR 317

                ..
gi 4503835  540 LC 541
Cdd:cd15909 318 FI 319
7tmF_FZD10 cd15037
class F frizzled subfamily 10, member of 7-transmembrane G protein-coupled receptors; This ...
221-541 0e+00

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: 528.40  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGA 300
Cdd:cd15037   1 VYWSKDDKRFAVVWIAIWSILCFFSSAFTVLTFLIDPQRFKYPERPIIFLSMCYCVYSVGYIIRLFAGAESIACDRDSGQ 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVA 380
Cdd:cd15037  81 LYVIQEGLESTGCTIVFLILYYFGMASSLWWVILTLTWFLAAGKKWGHEAIEANSSYFHLAAWAIPAVKTIMILVMRRVA 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  381 GDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 460
Cdd:cd15037 161 GDELTGVCYVGSMDVNALTGFVLIPLACYLIIGTSFILSGFVALFHIRRVMKTGGENTDKLEKLMVRIGVFSVLYTVPAT 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  461 CVIVCYVYERLNMDFWRLRATEQPCAAAAGPGGrRDCSLpGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSL 540
Cdd:cd15037 241 CVIACYFYERLNMDYWKILATQQKCKMDNQTKT-LDCVM-TSSIPAVEIFMVKIFMLLVVGITSGMWIWTSKTLQSWQNV 318

                .
gi 4503835  541 C 541
Cdd:cd15037 319 F 319
Frizzled pfam01534
Frizzled/Smoothened family membrane region; This family contains the membrane spanning region ...
222-544 2.29e-177

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: 504.06  E-value: 2.29e-177
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835    222 FWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVAC--DQEAG 299
Cdd:pfam01534   1 LFTEDEKKFARKWIGVWSALCFVSTLFTVLTFLIDWSRFRYPERPIIFLSLCYLLVSLGYLIRFVLGREDIACrkDGTGR 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835    300 ALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKV 379
Cdd:pfam01534  81 GSYLITQGTENLSCTVVFLLLYYFGMAASIWWVILTLTWFLAAGLKWGSEAIEKKSSYFHLAAWGIPAVLTITVLALGKV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835    380 AGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKT-GGTNTEKLEKLMVKIGVFSILYTVP 458
Cdd:pfam01534 161 DGDELTGICFVGNQNSDALRGFVLAPLLVYLLLGTYFLLAGFVSLFRIRRVLKKdGARATDKLEKLMVRIGVFSVLYTVP 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835    459 ATCVIVCYVYERLNMDFWRLRATEQPCAAAAGPggrrdCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQ 538
Cdd:pfam01534 241 ALIVIACYFYEYANRDSWELSWQYINCRAYGIP-----CLDEPESRPSFSVFMLKYFMSLVVGITSGFWVWSGKTLESWR 315

                  ....*.
gi 4503835    539 SLCYRK 544
Cdd:pfam01534 316 RFFRRL 321
7tmF_FZD4 cd15038
class F frizzled subfamily 4, member of 7-transmembrane G protein-coupled receptors; This ...
223-542 2.52e-159

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: 457.69  E-value: 2.52e-159
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  223 WSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEA--GA 300
Cdd:cd15038   3 FTQSDKEFADIWMAIWAGLCFISTLFTVLTFLIDSGRFKYPERPIIFLSMCYNIYSIAYIVRLLAGRESISCDLDSqtAV 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVA 380
Cdd:cd15038  83 SILIQEGLENTGCAIVFLLLYFFGMASSIWWVILTLTWFLAAGLKWGHEAIQMHSSYFHIAAWALPAVKTIVILVMRVVD 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  381 GDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 460
Cdd:cd15038 163 ADELTGLCYVGNQNLDALLGFVVAPLFTYLVIGTLFLIAGFVALFRIRSQLQRDGTKTDKLERLMVRIGIFSVLYTVPAT 242
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  461 CVIVCYVYERLNMDFWRLRATEqpcaaaagpggrrdcslpggSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSL 540
Cdd:cd15038 243 CVIACYFYEYSNRDLWYYGGSA--------------------ARPNMEVFMLKIFMSLVVGITSGMWIWSAKTLSSWRNF 302

                ..
gi 4503835  541 CY 542
Cdd:cd15038 303 FN 304
7tmF_FZD1_2_7-like cd15034
class F frizzled subfamilies 1, 2 and 7; member of 7-transmembrane G protein-coupled receptors; ...
221-538 4.58e-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: 429.84  E-value: 4.58e-148
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGaQSVACDQEAGA 300
Cdd:cd15034   1 MFFTEKEREFARLWIGIWSVLCAASTLFTVLTFLIDMDRFRYPERPIIFLSGCYFMVSIAYIVGFFLG-DKVACNGPFPP 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LY--VIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRK 378
Cdd:cd15034  80 GGpkTVTQGTKKEGCTILFMMLYFFSMASSIWWVILTLTWFLAAGLKWGHEAIEANSQYFHLAAWAVPAIKTIAILAMGK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  379 VAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVP 458
Cdd:cd15034 160 VDGDVLSGVCFVGLSDVDALRGFVLAPLFVYLLIGTSFLLAGFVSLFRIRTVMKHDGTKTDKLEKLMVRIGVFSVLYTVP 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  459 ATCVIVCYVYERLNMDFWRLRATEQPCAAAAGPGGRRDCSLPGGSvPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQ 538
Cdd:cd15034 240 ATIVIACYFYEQANRESWEKSWLSQNCKKYEDPCPCPPTPHPLDR-PDFTVFMIKYLMTLIVGITSGFWIWSGKTLQSWR 318
7tmF_FZD5_FZD8-like cd15035
class F frizzled subfamilies 5, 8 and related proteins; member of 7-transmembrane G ...
222-541 2.22e-141

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: 412.06  E-value: 2.22e-141
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  222 FWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEagal 301
Cdd:cd15035   2 FFSEDEKTFATFWIGLWSILCFISTLITVLTFLIDMQRFQYPERPIIFLSFCYFMVSVGYIIRLIVGHEAVACDGG---- 77
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  302 yVIQEGLenTG---CTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRK 378
Cdd:cd15035  78 -IIRYAT--TGpalCTVVFLLTYFFGMASSIWWVILSLTWFLAAGLKWGNEAISSYSQYFHLVAWLIPAVQTIAILALSA 154
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  379 VAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKT-GGTNTEKLEKLMVKIGVFSILYTV 457
Cdd:cd15035 155 VDGDPISGICYVGNQNLNNLRGFVLAPLVVYLILGTSFLLAGFVSLFRIRNVIKQqGGDKTDKLEKLMIRIGIFSVLYTV 234
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  458 PATCVIVCYVYERLNMDFWrLRATEQPCaaaagpggrrdCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTW 537
Cdd:cd15035 235 PATIVIACYFYEQHYREIW-EKSLNCPC-----------SPGSIKSRPEYSIFMLKYFMSLVVGITSGFWIWSGKTLDSW 302

                ....
gi 4503835  538 QSLC 541
Cdd:cd15035 303 KRFC 306
7tmF_Frizzled_SMO cd13951
class F frizzled/smoothened family, member of the 7-transmembrane G protein-coupled receptor ...
222-540 8.37e-138

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: 403.24  E-value: 8.37e-138
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  222 FWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGAL 301
Cdd:cd13951   2 LFTSSEKKFAEIWISAWSALCFLLTLFTLLTFLIDPSRFRYPERPIIFLALCYNFYSLGYLVRLVVGREGIACGKDEGKP 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  302 YV-IQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVA 380
Cdd:cd13951  82 YLlLVDGSGNAPCAIVFLLTYYFGMAASIWWVILTLTWFLSAGLKWSSEAIEKKSSYFHLVAWGLPAVLTIAVLVLRKVD 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  381 GDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPAT 460
Cdd:cd13951 162 GDELTGICFVGNQNLDALRGFVLAPLFLYLILGTVFLLCGFLSLFRIRSILSNDGKKTDKLEKLMLRIGIFAVLYTLPAL 241
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  461 CVIVCYVYERLNMDFWrLRATEQPCaaaagpggRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSL 540
Cdd:cd13951 242 IVIACYFYEYANRPDW-LRSWEPHS--------CCSPDCEILSRPSLAVFLLKYFMQLVIGITTGVWVWSKKTLLSWRRL 312
7tmF_FZD5 cd15249
class F frizzled subfamily 5, member of 7-transmembrane G protein-coupled receptors; This ...
222-538 5.10e-123

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: 365.42  E-value: 5.10e-123
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  222 FWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGAL 301
Cdd:cd15249   2 YFSQDERTFATFWIGLWSVLCFISTFTTVATFLIDMERFRYPERPIIFLSACYLFVSLGYIVRLVVGHESVACNREHNHI 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  302 YviqegLENTG---CTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRK 378
Cdd:cd15249  82 H-----YETTGpalCTIVFLLIYFFGMASSIWWVILSFTWFLAAGMKWGNEAIAGYSQYFHLAAWLIPSVKSIAVLALSS 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  379 VAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVP 458
Cdd:cd15249 157 VDGDPVAGICYVGNQNLNNLRGFVLAPLVVYLFTGTLFLLAGFVSLFRIRSVIKQGGTKTDKLEKLMIRIGIFTVLYTVP 236
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  459 ATCVIVCYVYERLNMDFWRlraTEQPCAAAAGPGGRRdcslpggSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQ 538
Cdd:cd15249 237 ATIVVACYVYEQHYRESWE---AALNCSCPGDDTQPR-------ARPDYAVFMLKYFMCLVVGITSGVWIWSGKTLESWR 306
7tmF_FZD1_insect cd15248
class F insect frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
221-545 8.29e-123

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: 365.68  E-value: 8.29e-123
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGaQSVACDQ---- 296
Cdd:cd15248   1 MFFPERERTFSRYWIGSWAAVCMASCLFTVLTFLIDSSRFRYPERPIVFLSVCYLMVAAAYVAGLGAG-DSVSCNEpfpp 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  297 -----EAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTI 371
Cdd:cd15248  80 pvklgRLQMVSTITQGTKTESCTVLFMVLYFFSMAASIWWVVLTLTWFLAAGLKWGHEAIEAKSHYFHLVAWAVPALKTI 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  372 VILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVF 451
Cdd:cd15248 160 SILAMGKVEGDVLSGVCYVGLWDMHALRGFVLAPLCVYLSLGTIFLLAGFISLFRIRTVMKHDGTKTDKLEKLMLRIGIF 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  452 SILYTVPATCVIVCYVYERLNMDFWRLRATEQPCAA---AAGPGGRRDCSLPGgsvPTVAVFMLKIFMSLVVGITSGVWV 528
Cdd:cd15248 240 SFLYTLPALIVLACLFYEQAHFDSWMLQWHRDICKPpswSIPACRATGSPEAR---PEFQVFMIKYLMSMIVGITSSVWI 316
                       330
                ....*....|....*..
gi 4503835  529 WSSKTFQTWQSLcYRKI 545
Cdd:cd15248 317 WSSKTLVSWRNF-YERL 332
7tmF_FZD8 cd15250
class F frizzled subfamily 8, member of 7-transmembrane G protein-coupled receptors; This ...
222-541 1.02e-121

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: 361.94  E-value: 1.02e-121
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  222 FWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGAL 301
Cdd:cd15250   2 YFSQEERTFTAFWIGLWSVLCFLSTFATVSTFLIDMERFKYPERPIIFLSACYLFVSLGYLVRLIAGHEKVACSRGALAE 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  302 yVIQEGLENTG---CTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRK 378
Cdd:cd15250  82 -VEHIHYETTGpalCTVVFLLIYFFGMASSIWWVILSLTWFLAAGMKWGNEAIAGYSQYFHLAAWLIPSVKSIAVLALSS 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  379 VAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVP 458
Cdd:cd15250 161 VDGDPVAGICYVGNQNLDNLRGFVLAPLVIYLFIGTMFLLAGFVSLFRIRSVIKQGGTKTDKLEKLMIRIGIFTVLYTVP 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  459 ATCVIVCYVYERLNMDFWRLrATEQPCAAAAGPGGRRdcslpggsvPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQ 538
Cdd:cd15250 241 ATIVVACYFYEQHNRQRWEI-THNCNCLRDQPDQARR---------PDYAVFMLKYFMCLVVGITSGVWTWSGKTLESWR 310

                ...
gi 4503835  539 SLC 541
Cdd:cd15250 311 ALC 313
7tmF_FZD7 cd15246
class F frizzled subfamily 7, member of 7-transmembrane G protein-coupled receptors; This ...
221-543 1.56e-118

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: 354.71  E-value: 1.56e-118
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGA 300
Cdd:cd15246   1 MYFKEEEVRFARLWVGIWSILCCASTLFTVLTYLVDMRRFSYPERPIIFLSGCYFMVAVAYAAGFLLEDRVVCVERFSDD 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LY-VIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKV 379
Cdd:cd15246  81 GYrTVAQGTKKEGCTILFMVLYFFGMASSIWWVILSLTWFLSAGMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMGQV 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  380 AGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPA 459
Cdd:cd15246 161 DGDLLSGVCYVGIYSVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRIGVFSVLYTVPA 240
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  460 TCVIVCYVYERLNMDFWRLRATEQPCAAAAGPggrrdcsLPGGSV----PTVAVFMLKIFMSLVVGITSGVWVWSSKTFQ 535
Cdd:cd15246 241 TIVLACYFYEQAFRETWEKTWLLQTCKRYAVP-------CPNNNFapmsPDFTVFMIKYLMTMIVGITSGFWIWSGKTLQ 313

                ....*...
gi 4503835  536 TWQSLCYR 543
Cdd:cd15246 314 SWRRFYHR 321
7tmF_FZD2 cd15245
class F frizzled subfamily 2, member of 7-transmembrane G protein-coupled receptors; This ...
221-550 4.55e-116

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: 348.16  E-value: 4.55e-116
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGaQSVACD---QE 297
Cdd:cd15245   1 MFFSQDEIRFARIWILIWSVLCCASTFFTVTTYLVDMQRFRYPERPIIFLSGCYTMVSVAYIAGFVLG-DKVVCNerfSE 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  298 AGALYVIQeGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLR 377
Cdd:cd15245  80 DGYKTVVQ-GTKKEGCTILFMMLYFFSMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAVKTITILAMG 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  378 KVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTV 457
Cdd:cd15245 159 QIDGDLLSGVCFVGLNNIDPLRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLERLMVRIGVFSVLYTV 238
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  458 PATCVIVCYVYERLNMDFWRLRATEQPCAAAAGPggrrdCSLPGGS--VPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQ 535
Cdd:cd15245 239 PATIVIACYFYEQAFRQHWERSWISQNCKSLAIP-----CPLQYTPrmTPDFTVYMIKYLMTLIVGITSGFWIWSGKTLH 313
                       330
                ....*....|....*
gi 4503835  536 TWQSLCYRKIAAGRA 550
Cdd:cd15245 314 SWRKFYTRLTNSRQG 328
7tmF_FZD1 cd15247
class F mammalian frizzled subfamily 1, member of 7-transmembrane G protein-coupled receptors; ...
211-543 3.85e-113

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: 341.25  E-value: 3.85e-113
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  211 CAPRCGPGVeVFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQ 290
Cdd:cd15247   2 CEPGRVHGL-MYFGPEELRFARIWIGIWSVLCCASTLFTVLTYLVDMKRFSYPERPIIFLSGCYTMVAIAYIAGFLLEDK 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  291 SVACDQ--EAGALYVIQeGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPAL 368
Cdd:cd15247  81 VVCNDKfaEDGIKTVAQ-GTKKEGCTILFMMLYFFSMASSIWWVILSLTWFLAAGMKWGHEAIEANSQYFHLAAWAVPAI 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  369 KTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKI 448
Cdd:cd15247 160 KTITILAVGQVDGDVLSGVCFVGINNVDALRGFVLAPLFVYLFIGTSFLLAGFVSLFRIRTIMKHDGTKTEKLEKLMVRI 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  449 GVFSILYTVPATCVIVCYVYERLNMDFWRLRATEQPCAAAAGPGGRRdcSLPGGSvPTVAVFMLKIFMSLVVGITSGVWV 528
Cdd:cd15247 240 GIFSVLYTVPATIVIACYFYEQAFREQWERSWISQSCKTYAIPCPAH--SHPPMS-PDFTVFMIKYLMTLIVGITSGFWI 316
                       330
                ....*....|....*
gi 4503835  529 WSSKTFQTWQSLCYR 543
Cdd:cd15247 317 WSGKTLNSWRKFYTR 331
7tmF_FZD3_FZD6-like cd15910
class F frizzled subfamilies 3, 6 and related proteins; member of 7-transmembrane G ...
221-537 1.15e-93

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: 290.22  E-value: 1.15e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGaQSVACDQEAGA 300
Cdd:cd15910   1 MYFGDDELMFARYFIGVVSILCLLATLFTFLTFLIDVNRFRYPERPIIFYAVCYFVVSLIFFVGFLLG-DDVACNHAIMD 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LY---VIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLR 377
Cdd:cd15910  80 ENngaTVVEGSRNKACTILFMILYFFTMAGTVWWVILTITWFLAAGFKWGSEAIEKKALYFHALAWGIPGVLTMVLLATN 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  378 KVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTV 457
Cdd:cd15910 160 KIEGDNISGVCFVGLYDSDGLRFFVLLPLCLYVLVGMSLLLAGIICLNRVRKSIHDDETNQEKLAKFMIRIGVFSILYLV 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  458 PATCVIVCYVYERLNMDFW-------RLRATEQPCAAAAgpggrrdcslPGGSVPTVAVFMLKIFMSLVVGITSGVWVWS 530
Cdd:cd15910 240 PLLTLIGCYAYEQSNRKSWestwvvrNCRRYHIPCPQLA----------QGNPRPGLFLFCIKYLMTLIVGIPPVFWVGS 309

                ....*..
gi 4503835  531 SKTFQTW 537
Cdd:cd15910 310 KKTCAEW 316
CRD_FZ9 cd07463
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 9 (Fz9) receptor; The cysteine-rich ...
35-161 1.15e-88

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: 269.97  E-value: 1.15e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   35 GAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPM 114
Cdd:cd07463   1 RAAKCQPVVIPMCRGIGYNLTRMPNFLGHDSQREAAIKLNEFAPLVEYGCHVHLRFFLCSLYAPMCTDQVSTSIPACRPM 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4503835  115 CEQARLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAPENATA 161
Cdd:cd07463  81 CEQARQKCSPIMEQFNFGWPESLDCSRLPTRNDPNALCMEAPENATA 127
7tmF_FZD3 cd15033
class F frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; This ...
221-539 4.27e-87

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: 273.36  E-value: 4.27e-87
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAgAQSVACDQEAGA 300
Cdd:cd15033   1 MYFRREELSFARYFIGVISIVCLSATLFTFLTFLIDVTRFRYPERPIIFYAVCYMMVSLIFFIGFLL-EDRVACNAASPG 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  301 LY---VIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLR 377
Cdd:cd15033  80 QYkasTVTQGSHNKACTMLFMVLYFFTMAGSVWWVILTITWFLAAVPKWGSEAIEKKALLFHASAWGIPGTLTIILLAMN 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  378 KVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTV 457
Cdd:cd15033 160 KIEGDNISGVCFVGLYDVDALRYFVLAPLCLDVVVGVSLLLAGIISLNRVRIEIPLEKENQDKLVKFMIRIGVFSVLYLV 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  458 PATCVIVCYVYERLNMDFWRLRATEQPCAAAAGPggrrdC--SLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQ 535
Cdd:cd15033 240 PLLVVIGCYFYEQAYRGVWETTWVQERCREYHIP-----CpyKVTQTSRPDLILFLMKYLMALVVGIPSVFWVGSKKTCF 314

                ....
gi 4503835  536 TWQS 539
Cdd:cd15033 315 EWAS 318
7tmF_FZD6 cd15032
class F frizzled subfamily 6, member of 7-transmembrane G protein-coupled receptors; This ...
221-541 1.29e-85

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: 269.41  E-value: 1.29e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  221 VFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGaQSVAC---DQE 297
Cdd:cd15032   1 MYFKSDELDFAKSFIGIVSIFCLCATLFTFLTFLIDVKRFRYPERPIIYYSVCYSIVSLMYFIGFLLG-NSTACnkaDEK 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  298 AGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLR 377
Cdd:cd15032  80 LELGDTVVLGSQNKACTVLFMLLYFFTMAGTIWWVILTITWFLAAGRKWSCEAIEQKALWFHAVAWGIPGFLTIMLLAMN 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  378 KVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTV 457
Cdd:cd15032 160 KVEGDNISGVCFVGLYDLDASRYFVLLPLCLCVFVGLSLLLAGIISLNHVRQVIQHDGRNQEKLKKFMIRIGVFSGLYLV 239
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  458 PATCVIVCYVYERLNMDFWRLRATEQPCAAAAGPGGRRdcsLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTW 537
Cdd:cd15032 240 PLVTLLGCYVYEQVYRRTWEITWVSDHCQQYHIPCPYQ---AKAVARPELALFLIKYLMTLIVGISAVFWVGSKKTCSEW 316

                ....
gi 4503835  538 QSLC 541
Cdd:cd15032 317 ASFF 320
CRD_FZ9_like cd07457
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 9; The cysteine-rich ...
37-157 6.56e-75

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: 234.31  E-value: 6.56e-75
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   37 APCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCE 116
Cdd:cd07457   1 GKCERITIPMCQGIGYNMTRMPNLLGHESQSEAAISIHEFAPLVQYGCAEHLRFFLCSLYAPMCTEQVSIPIPACRSMCE 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 4503835  117 QARLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAPE 157
Cdd:cd07457  81 QARDKCSPIMEQFSFSWPDSLDCDRLPRKNDPKDLCMEAPN 121
CRD_FZ10 cd07462
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 10 (Fz10) receptor; The cysteine-rich ...
35-160 1.29e-72

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: 228.36  E-value: 1.29e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   35 GAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPM 114
Cdd:cd07462   1 GEGRCQPIEIPMCKDIGYNMTRMPNLMGHENQREAAIQLHEFAPLVEYGCHSHLKFFLCSLYAPMCTEQVSTPIPACRVM 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 4503835  115 CEQARLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAPENAT 160
Cdd:cd07462  81 CEQARLKCSPIMEQFNFKWPDSLDCSKLPNKNDPNYLCMEAPNNGT 126
7tmF_FZD3_insect cd15031
class F insect frizzled subfamily 3, member of 7-transmembrane G protein-coupled receptors; ...
222-539 5.65e-55

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: 188.82  E-value: 5.65e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  222 FWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGA----QSVACDQE 297
Cdd:cd15031   2 FYTTRQKKLVESWMLVLSAVSFILTLFALVTFWAEPTRFGYPERPVLFMALCYNLISLCYLERGILGTftncSARSLAID 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  298 AGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLR 377
Cdd:cd15031  82 CDDRYLRQDCLLTPQCLASFIITYYLSLSAASWWLIFALCWYLSSAKKWSSEALEKKSGLFHVLAWVPPLAPPIAALLLE 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  378 KVAGDELTGLCYVASTDAAAltgFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLekLMVKIGVFSILYTV 457
Cdd:cd15031 162 RVSASELTGTCTASGFVESS---ISELPALILLLLGLYLTIAALRSLLSLQQQLQSRLAHAPQR--ILARVSIFSLLYLI 236
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  458 PATCVIVCYVYERLNmdfwrlrATEQPCAAaagpgGRRDCSLPGGSVP--TVAVFMLKIFMSLVVGITSGVWVWSSKTFQ 535
Cdd:cd15031 237 PAAAALICKLCERWL-------QPVPECNA-----LQEDCAPPATDNEflSALPALLRVFFFLIGGTATGLWLWSRKSCE 304

                ....
gi 4503835  536 TWQS 539
Cdd:cd15031 305 SWRS 308
7tmF_SMO_homolog cd15030
class F smoothened family membrane region, a homolog of frizzled receptors; This group ...
234-537 4.97e-51

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: 178.64  E-value: 4.97e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  234 WMAVWSALCFFSTAFTVLTFLLEPHRF-QYPERPIIFLSMCYNVYSLAFLIRAVAGA-QSVACdQEAGALYVIQ-EGLEN 310
Cdd:cd15030  14 FIAVFASVCLLCTLFTVLTFFIDWKNSnRYPAVILFYINACFFIGSIGWLAQFLPGArEDIVC-RKDGTMRLGEpSAGEN 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  311 TGCTLVFLLLYYFGMASSLWWVVLTLTW---FLAAGKKwgHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTGL 387
Cdd:cd15030  93 LSCVVIFVLVYYFLMAGCVWFVILTYAWhmsFKALGTI--QDRLDKKTAYFHLIAWSLPLVLTITIMALGQVDGDSVSGI 170
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  388 CYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIrKIMKTGGTNT---EKLEKLMVKIGVFSILYTVPATCVIV 464
Cdd:cd15030 171 CFVGYKNHMYRAGFVLAPVGLVLVIGGYFLVRGLYTLIKL-KISSPEILSEkasSKIRETIVRLGIFAFLALGFVLITFA 249
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  465 CYVYERLNMDFWRL--------RATEQpcAAAAGPGGRRDCSLpgGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQT 536
Cdd:cd15030 250 CHVYEFFNQAEWEKsfrdyivcEANVT--IAEQTNGDIPECEL--KSRPSLAMLQLHLLALFGAGIAMSSWVWTRATLET 325

                .
gi 4503835  537 W 537
Cdd:cd15030 326 W 326
CRD_FZ4 cd07448
Cysteine-rich Wnt-binding domain of the frizzled 4 (Fz4) receptor; The cysteine-rich domain ...
39-156 6.97e-51

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: 171.11  E-value: 6.97e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQA 118
Cdd:cd07448   4 CEPIRIEMCQGLGYNVTRMPNLVGHELQTDAELQLQTFTPLIQYGCSSQLKFFLCSVYVPMCTEKVPVPIGPCRPLCLSV 83
                        90       100       110
                ....*....|....*....|....*....|....*...
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAP 156
Cdd:cd07448  84 KKRCLPVLKEFGFPWPEALNCSKFPPQNNHNHMCMEGP 121
FRI smart00063
Frizzled; Drosophila melanogaster frizzled mediates signalling that polarises a precursor cell ...
39-155 2.52e-48

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: 164.02  E-value: 2.52e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835      39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVStPIPACRPMCEQA 118
Cdd:smart00063   1 CEPITIPLCKDLGYNLTSMPNLLGHTTQEEAGLELEQFHPLLNVQCSPDLRFFLCSVYAPICTEDLR-PILPCRSLCEAA 79
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 4503835     119 RLRCAPIMEQFNFGWPDSLDCARLPTRNDphaLCMEA 155
Cdd:smart00063  80 REGCEPLMEKFGFPWPEFLRCDRFPVQEE---LCMDP 113
CRD_FZ5_like cd07456
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 5; The cysteine-rich ...
39-157 4.10e-45

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: 155.63  E-value: 4.10e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQA 118
Cdd:cd07456   2 CEEITIPMCKGIGYNMTYMPNQFNHDTQEEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYDKPLPPCRSVCERA 81
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAPE 157
Cdd:cd07456  82 RDGCAPIMRQYGFAWPERMSCDALPEGGDPDNLCMDRNN 120
CRD_FZ8 cd07461
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 8 (Fz8) receptor; The cysteine-rich ...
39-154 2.40e-41

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: 145.51  E-value: 2.40e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQA 118
Cdd:cd07461   5 CQEITVPLCKGIGYNYTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLKFFLCSMYTPICLEDYKKPLPPCRSVCERA 84
                        90       100       110
                ....*....|....*....|....*....|....*.
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCME 154
Cdd:cd07461  85 KAGCAPLMRQYGFPWPDRMRCDLLPEQGNPDTLCMD 120
CRD_FZ5 cd07460
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 5 (Fz5) receptor.proteins; The ...
36-154 2.44e-41

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: 145.54  E-value: 2.44e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   36 AAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMC 115
Cdd:cd07460   2 ALVCQEITVPMCKGIGYNLTYMPNQFNHDTQDEAGLEVHQFWPLVEIQCSPDLRFFLCSMYTPICLPDYRKPLPPCRSVC 81
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 4503835  116 EQARLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCME 154
Cdd:cd07460  82 ERAKAGCSPLMRQYGFAWPERMNCDRLPVLGDPETLCMD 120
CRD_FZ cd07066
CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain; CRD_FZ is an essential ...
39-157 7.02e-41

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: 144.19  E-value: 7.02e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQA 118
Cdd:cd07066   2 CEPIPLPLCRGLPYNTTRFPNLLGHESQEEAEQELESFTPLVNSGCHPDLRFFLCSLYFPECTPDGDRPIPPCRSLCEEV 81
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLPTRNDpHALCMEAPE 157
Cdd:cd07066  82 RDSCEPLMLAFGFPWPEPLDCDRFPDSNE-EGLCISPPG 119
CRD_FZ1_like cd07458
Cysteine-rich Wnt-binding domain (CRD) of receptors similar to frizzled 1; The cysteine-rich ...
39-157 1.92e-37

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: 134.85  E-value: 1.92e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTdQVSTPIPACRPMCEQA 118
Cdd:cd07458   3 CEPITIPLCTDIPYNMTIFPNLLGHTKQEDAGLEVHQFYPLVKVQCSPDLKFFLCSVYAPVCT-VLERPIPPCRSLCESA 81
                        90       100       110
                ....*....|....*....|....*....|....*....
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLPTrNDPHALCMEAPE 157
Cdd:cd07458  82 RQGCEALMNKFGFQWPESLDCEKFPV-HGAGDLCVGENT 119
Fz pfam01392
Fz domain; Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This ...
39-143 6.03e-35

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: 127.68  E-value: 6.03e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835     39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQ-----GEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCT--DQVSTPIPAC 111
Cdd:pfam01392   1 CEPITLPMCLGLGYNATVFPNLLGHQTQeeaelSLAYLVLSEFEPLVDLSCSPSLRLFLCSLYFPPCTlgPSPKPVCPPC 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 4503835    112 RPMCEQARLRCAPIME--QFNFGWPDSLDCARLP 143
Cdd:pfam01392  81 RSLCEEVRYGCEPLLEeaKFGFSWPEFLDCDSLP 114
CRD_SFRP4 cd07442
Cysteine-rich domain of the secreted frizzled-related protein 4 (SFRP4), a Wnt antagonist; The ...
36-143 1.46e-33

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: 124.37  E-value: 1.46e-33
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   36 AAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCT-DQVSTPIPACRPM 114
Cdd:cd07442   2 GAPCEAVRIPMCRHMPWNITRMPNHLHHSTQENAVLAIEQYEELVDTGCSPVLPFFLCAMYAPICTlEFLYDPIKPCRSV 81
                        90       100
                ....*....|....*....|....*....
gi 4503835  115 CEQARLRCAPIMEQFNFGWPDSLDCARLP 143
Cdd:cd07442  82 CQRARDGCEPIMRRYNHSWPESLACDDLP 110
CRD_SFRP2 cd07446
Cysteine-rich domain of the secreted frizzled-related protein 2 (SFRP2), a regulator of Wnt ...
39-153 3.08e-31

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: 118.09  E-value: 3.08e-31
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPM--CRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCE 116
Cdd:cd07446   5 CKPIPANMllCHGIEYTNMRLPNLLGHETMKEVLQQAGSWIPLVQKQCHPDTKKFLCSLFAPVCLDDLDEAIQPCRSLCE 84
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 4503835  117 QARLRCAPIMEQFNFGWPDSLDCARLPTRNDphaLCM 153
Cdd:cd07446  85 AVKDGCAPVMSAFGFPWPDMLDCTRFPLDND---LCI 118
CRD_FZ2 cd07464
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 2 (Fz2) receptor; The cysteine-rich ...
39-153 5.17e-30

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: 114.41  E-value: 5.17e-30
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTdQVSTPIPACRPMCEQA 118
Cdd:cd07464   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSLELRFFLCSMYAPVCT-VLEQAIPPCRSICERA 83
                        90       100       110
                ....*....|....*....|....*....|....*
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLPtRNDPHALCM 153
Cdd:cd07464  84 RQGCEALMNKFGFQWPERLRCENFP-RHGAEQICV 117
CRD_FZ7 cd07466
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 7 (Fz7) receptor; The cysteine-rich ...
39-143 1.09e-29

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: 113.64  E-value: 1.09e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTdQVSTPIPACRPMCEQA 118
Cdd:cd07466   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSPELKFFLCSMYAPVCT-VLEQAIPPCRSLCERA 83
                        90       100
                ....*....|....*....|....*
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLP 143
Cdd:cd07466  84 RQGCEALMNKFGFQWPERLRCENFP 108
CRD_FZ1 cd07465
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 1 (Fz1) receptor; The cysteine-rich ...
39-143 4.01e-29

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: 112.07  E-value: 4.01e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTdQVSTPIPACRPMCEQA 118
Cdd:cd07465   5 CQPISIPLCTDIAYNQTIMPNLLGHTNQEDAGLEVHQFYPLVKVQCSAELKFFLCSMYAPVCT-VLEQALPPCRSLCERA 83
                        90       100
                ....*....|....*....|....*
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLP 143
Cdd:cd07465  84 RQGCEALMNKFGFQWPDTLRCEKFP 108
CRD_SFRP3 cd07441
Cysteine-rich domain of the secreted frizzled-related protein 3 (SFRP3, alias FRZB), a Wnt ...
36-143 1.38e-27

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: 107.44  E-value: 1.38e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   36 AAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCT-DQVSTPIPACRPM 114
Cdd:cd07441   1 AASCEPVRIPMCKSMPWNMTKMPNHLHHSTQANAVLAIEQFEGLLGTQCSPDLLFFLCAMYAPICTiDFQHEPIKPCKSV 80
                        90       100
                ....*....|....*....|....*....
gi 4503835  115 CEQARLRCAPIMEQFNFGWPDSLDCARLP 143
Cdd:cd07441  81 CERARAGCEPVLIRYRHTWPESLACEELP 109
CRD_FZ3 cd07449
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 3 (Fz3) receptor; The cysteine-rich ...
39-149 2.71e-27

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: 106.63  E-value: 2.71e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPaCRPMCEQA 118
Cdd:cd07449   5 CEPITLRMCQDLPYNTTFMPNLLNHYDQQTAALAMEPFHPMVNLECSRDFRPFLCALYAPVCMEYGRVTLP-CRRLCQRA 83
                        90       100       110
                ....*....|....*....|....*....|.
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLPTRNDPH 149
Cdd:cd07449  84 YSECSKLMEMFGVPWPEDMECSRFPDCDEPY 114
CRD_LIN_17 cd07454
Cysteine-rich domain (CRD) of LIN_17; A cysteine-rich domain (CRD) is an essential component ...
39-158 3.90e-27

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: 106.40  E-value: 3.90e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQA 118
Cdd:cd07454   5 CIPIDIELCKDLPYNYTYFPNTILHNDQHTLQTHTEHFKPLMKTKCHPHIHFFICSVFAPMCPIGMPQAVTSCKSVCEQV 84
                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLPTRNDphaLCMEAPEN 158
Cdd:cd07454  85 KADCFSILEEFGIGWPEPLNCAQFPDPPE---LCMKPTED 121
CRD_SFRP5 cd07444
Cysteine-rich domain of the secreted frizzled-related protein 5 (SFRP5), a regulator of Wnt ...
36-153 5.25e-27

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: 105.80  E-value: 5.25e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   36 AAPCQAVEIP----MCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQvstPIPAC 111
Cdd:cd07444   2 SKQPQCVDIPadlpLCHNVGYKRMRLPNLLEHESMAEVKQQASSWVPLLAKRCHADTQVFLCSLFAPVCLDR---PIYPC 78
                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 4503835  112 RPMCEQARLRCAPIMEQFNFGWPDSLDCARLPTRNDphaLCM 153
Cdd:cd07444  79 RSLCEAVRDSCAPVMESYGFPWPEMLHCHKFPLDND---LCI 117
CRD_sizzled cd07452
Cysteine-rich domain of the sizzled protein; The cysteine-rich domain (CRD) is an essential ...
43-147 2.31e-24

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: 98.80  E-value: 2.31e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   43 EIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDqvsTPIPACRPMCEQARLRC 122
Cdd:cd07452  15 EMSMCQDVGYSEMRLPNLLGHTSMAEVVPKSADWQTLLHTGCHPHARTFLCSLFAPVCLD---TFIQPCRSMCVAVRDSC 91
                        90       100
                ....*....|....*....|....*
gi 4503835  123 APIMEQFNFGWPDSLDCARLPTRND 147
Cdd:cd07452  92 APVLACHGHSWPESLDCDRFPAGED 116
CRD_crescent cd07453
Cysteine-rich domain of the crescent protein; The cysteine-rich domain (CRD) is an essential ...
37-163 9.84e-24

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: 96.93  E-value: 9.84e-24
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   37 APCQAVEIPM--CRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQvstPIPACRPM 114
Cdd:cd07453   1 SPCMRIPKSMalCYDIGYSEMRIPNLLEHETMAEVIQQSSSWLPLLARECHPDARIFLCSLFAPICWDR---PIYPCRSL 77
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 4503835  115 CEQARLRCAPIMEQFNFGWPDSLDCARLPTRNDphaLCMEAPENATAGP 163
Cdd:cd07453  78 CEAVRSSCAPLMACYGYPWPEILHCDKFPVDHD---LCISPQFIDTLSP 123
CRD_SFRP1 cd07443
Cysteine-rich domain of the secreted frizzled-related protein 1 (SFRP1), a regulator of Wnt ...
38-160 1.01e-23

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: 96.51  E-value: 1.01e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   38 PCQAVEIP----MCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQvstPIPACRP 113
Cdd:cd07443   4 PPQCVDIPadlrLCHNVGYKKMVLPNLLDHETMAEVKQQASSWVPLLNKNCHKGTQVFLCSLFAPVCLDR---PVYPCRW 80
                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 4503835  114 MCEQARLRCAPIMEQFNFGWPDSLDCARLPTRNDphALCMEAPeNAT 160
Cdd:cd07443  81 LCEAVRDSCEPVMQFFGFYWPEMLKCDKFPEGEV--CIAMTPP-NAT 124
CRD_corin_2 cd07888
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
39-153 1.64e-23

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: 95.85  E-value: 1.64e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAE--LAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCE 116
Cdd:cd07888   2 CEPITLELCMNLPYNTTRYPNYLGHRTQKEASISweSSLFPALVQTNCYKYLMFFACTILVPKCDPVTQQRIPPCRSLCR 81
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 4503835  117 QARLRCAPIMEQFNFGWPDSLDCARLPTRNDPHALCM 153
Cdd:cd07888  82 NSKERCESVLGIVGLQWPEDTDCAQFPEENSDNQTCL 118
CRD_FZ6 cd07450
Cysteine-rich Wnt-binding domain (CRD) of the frizzled 6 (Fz6) receptor; The cysteine-rich ...
39-143 8.95e-19

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: 82.51  E-value: 8.95e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   39 CQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPaCRPMCEQA 118
Cdd:cd07450   5 CEPITVPRCLKMPYNMTFFPNLMGHYDQDIAAVEMEPFLPLANLRCSPNVHTFLCQAFVPTCTEQIHVVRP-CRELCEKV 83
                        90       100
                ....*....|....*....|....*
gi 4503835  119 RLRCAPIMEQFNFGWPDSLDCARLP 143
Cdd:cd07450  84 YSDCKKLIDTFGISWPEELECDRLQ 108
CRD_Carboxypeptidase_Z cd07447
Cysteine-rich domain of carboxypeptidase Z, a member of the carboxypeptidase E family; The ...
37-147 2.27e-10

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: 58.61  E-value: 2.27e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   37 APCQAVEIPMCRGIGYNLTRMPNLLGHTSQ-----GEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMC-TDQVSTPipa 110
Cdd:cd07447   2 ATCTDLLLSYCSDVSYTQTTFPNLLGHRSRevteaGAEYLLLSVLHGLLGGECNPDIRLLGCSVLAPRCeNDKVIKP--- 78
                        90       100       110
                ....*....|....*....|....*....|....*..
gi 4503835  111 CRPMCEQARLRCAPIMEQFNFGWPDSLDCARLPTRND 147
Cdd:cd07447  79 CRSTCEALRKRCSHAFDAIQMAWPYFLDCDRFFAGEQ 115
CRD_Collagen_XVIII cd07455
Cysteine-rich domain of the variant 3 of collagen XVIII (V3C18 ); The cysteine-rich domain ...
36-147 2.02e-09

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: 55.59  E-value: 2.02e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   36 AAPCQAV--EIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRP 113
Cdd:cd07455   2 RPRCLPVpsSLPFCSRLGIRSFWLPNFLNHTSVEEVRAVLAEWAWLLESGCHPSLEWFFCLLLVPSCGGGPPPPPPPCRQ 81
                        90       100       110
                ....*....|....*....|....*....|....
gi 4503835  114 MCEQARLRCAPIMEQFNFgwpdSLDCARLPTRND 147
Cdd:cd07455  82 FCEVLQDSCWNLLEGGRL----PVACASLPEQED 111
CRD_corin_1 cd07445
One of two cysteine-rich domains of the corin protein, a type II transmembrane serine protease ...
84-141 4.29e-08

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: 52.24  E-value: 4.29e-08
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835   84 CHSHLRFFLCSLYAPMCTDQV--STPIPACRPMCEQARLRCAPIMEQFNFGWPDSLDCAR 141
Cdd:cd07445  49 CYQHIMLFGCSLALPECISDGddRHGLLPCRSFCEAAKEGCEPVLGMVNASWPDFLRCSQ 108
7tmB2_Adhesion cd15040
adhesion receptors, subfamily B2 of the class B family of seven-transmembrane G ...
229-454 1.67e-06

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: 49.49  E-value: 1.67e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  229 DFALVWM-AVWSALCFFSTAFTVLTFLLEPhRFQYPERPIIFLSMCYNV--YSLAFLIravagaqsvacdqeagalyVIQ 305
Cdd:cd15040   1 EKALSIItYIGCGLSLLGLLLTIITYILFR-KLRKRKPTKILLNLCLALllANLLFLF-------------------GIN 60
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  306 EGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAgKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELT 385
Cdd:cd15040  61 STDNPVLCTAVAALLHYFLLASFMWMLVEALLLYLRL-VKVFGTYPRHFILKYALIGWGLPLIIVIITLAVDPDSYGNSS 139
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  386 GLCYVaSTDAAALTGFvLVPLSgyLVLGSSFLLTGFValfhIRKIMKTG-GTNTEKLEKLMVKIGVFSIL 454
Cdd:cd15040 140 GYCWL-SNGNGLYYAF-LGPVL--LIILVNLVIFVLV----LRKLLRLSaKRNKKKRKKTKAQLRAAVSL 201
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
307-468 5.30e-06

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


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 48.19  E-value: 5.30e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  307 GLENTGCTLVFLLLYYFGMASSLWWVVLTLTWF--LAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGD-- 382
Cdd:cd14964  65 SRPQALCYLIYLLWYGANLASIWTTLVLTYHRYfaLCGPLKYTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRyn 144
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  383 ELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALF-HIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPATC 461
Cdd:cd14964 145 TLTGSCYLICTTIYLTWGFLLVSFLLPLVAFLVIFSRIVLRLRrRVRAIRSAASLNTDKNLKATKSLLILVITFLLCWLP 224

                ....*..
gi 4503835  462 VIVCYVY 468
Cdd:cd14964 225 FSIVFIL 231
7tm_classB cd13952
class B family of seven-transmembrane G protein-coupled receptors; The class B of ...
239-454 2.08e-05

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: 46.44  E-value: 2.08e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  239 SALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRavagaqsvacdqeagalYVIQEGLENTGCTLVFL 318
Cdd:cd13952  12 CSLSLVGLLLTIITYLLFPKLRNLRGKILINLCLSLLLAQLLFLIG-----------------QLLTSSDRPVLCKALAI 74
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  319 LLYYFGMASSLWWVVLTLTWFLAAGKKWGHEaIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTGL----CYVaSTD 394
Cdd:cd13952  75 LLHYFLLASFFWMLVEAFDLYRTFVKVFGSS-ERRRFLKYSLYGWGLPLLIVIITAIVDFSLYGPSPGYggeyCWL-SNG 152
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4503835  395 AAALTGFvLVPLSgyLVLGSSFLLTGFVAlFHIRKIMKTGGTNTEKlEKLMVKIGVFSIL 454
Cdd:cd13952 153 NALLWAF-YGPVL--LILLVNLVFFILTV-RILLRKLRETPKQSER-KSDRKQLRAYLKL 207
CRD_SMO cd07451
Cysteine-rich domain of the smoothened receptor (Smo) integral membrane protein; The ...
91-146 9.27e-03

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: 36.58  E-value: 9.27e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 4503835   91 FLCSLYAPMC-TDQVSTPipaCRPMCEQARLRCApIMEQFNfGWPDSL--DCARLPTRN 146
Cdd:cd07451  60 LLCALYMPKCeNGKVELP---SQEMCQATRGPCK-IVENER-GWPDFLrcDNDRFPPRG 113
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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