KEGG   PATHWAY: hsa04310Help
Entry
hsa04310                    Pathway                                

Name
Wnt signaling pathway - Homo sapiens (human)
Description
Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility. WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin.
Class
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
Wnt signaling pathway
hsa04310

All organismsOrtholog table
Module
SCF-BTRC complex [PATH:hsa04310]
Wnt signaling [PATH:hsa04310]
Disease
H00078  
Frontotemporal lobar degeneration (FTLD)
H00409  
Type II diabetes mellitus
H00450  
Sclerosing bone dysplasias
H00451  
Osteoporosis-pseudoglioma syndrome (OPPG)
H00589  
Familial exudative vitreoretinopathy (FEVR)
H00598  
46,XX disorders of sex development (Disorders of gonadal development)
H00600  
46,XX disorders of sex development (Other)
H00607  
46,XY disorders of sex development (Disorders of gonadal development)
H00625  
Tooth agenesis
H00636  
Tetra-amelia
H00646  
Odontoonychodermal dysplasia
H00681  
Acne inversa
H00810  
Progressive myoclonic epilepsy (PME/ EPM)
H00857  
Oligodontia-colorectal cancer syndrome
H00881  
Li-Fraumeni syndrome
H00934  
Caudal duplication anomaly
H00947  
Pilomatricoma
H00949  
Focal dermal hypoplasia
H00979  
Caudal regression syndrome and Sirenomelia
H01007  
Choroid plexus papilloma
H01023  
Juvenile polyposis syndrome
H01025  
Familial adenomatous polyposis
H01037  
Vesicoureteral reflux
H01307  
Nonsyndromic congenital nail disorder (NDNC)
Drug
D10094  
Blosozumab (USAN)
D10156  
Romosozumab (USAN)
D10410  
Vantictumab (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
64840  
PORCN; porcupine homolog (Drosophila) [KO:K00181]
7471  
WNT1; wingless-type MMTV integration site family, member 1 [KO:K03209]
7472  
WNT2; wingless-type MMTV integration site family member 2 [KO:K00182]
7482  
WNT2B; wingless-type MMTV integration site family, member 2B [KO:K00182]
7473  
WNT3; wingless-type MMTV integration site family, member 3 [KO:K00312]
89780  
WNT3A; wingless-type MMTV integration site family, member 3A [KO:K00312]
54361  
WNT4; wingless-type MMTV integration site family, member 4 [KO:K00408]
7474  
WNT5A; wingless-type MMTV integration site family, member 5A [KO:K00444]
81029  
WNT5B; wingless-type MMTV integration site family, member 5B [KO:K00444]
7475  
WNT6; wingless-type MMTV integration site family, member 6 [KO:K00445]
7476  
WNT7A; wingless-type MMTV integration site family, member 7A [KO:K00572]
7477  
WNT7B; wingless-type MMTV integration site family, member 7B [KO:K00572]
7478  
WNT8A; wingless-type MMTV integration site family, member 8A [KO:K00714]
7479  
WNT8B; wingless-type MMTV integration site family, member 8B [KO:K00714]
7483  
WNT9A; wingless-type MMTV integration site family, member 9A [KO:K01064]
7484  
WNT9B; wingless-type MMTV integration site family, member 9B [KO:K01064]
7480  
WNT10B; wingless-type MMTV integration site family, member 10B [KO:K01357]
80326  
WNT10A; wingless-type MMTV integration site family, member 10A [KO:K01357]
7481  
WNT11; wingless-type MMTV integration site family, member 11 [KO:K01384]
51384  
WNT16; wingless-type MMTV integration site family, member 16 [KO:K01558]
9350  
CER1; cerberus 1, DAN family BMP antagonist [KO:K01645]
11197  
WIF1; WNT inhibitory factor 1 [KO:K01691]
50964  
SOST; sclerostin [KO:K16834]
22943  
DKK1; dickkopf WNT signaling pathway inhibitor 1 [KO:K02165]
27123  
DKK2; dickkopf WNT signaling pathway inhibitor 2 [KO:K02165]
27121  
DKK4; dickkopf WNT signaling pathway inhibitor 4 [KO:K02165]
6422  
SFRP1; secreted frizzled-related protein 1 [KO:K02166]
6423  
SFRP2; secreted frizzled-related protein 2 [KO:K02176]
6424  
SFRP4; secreted frizzled-related protein 4 [KO:K02185]
6425  
SFRP5; secreted frizzled-related protein 5 [KO:K02222]
8321  
FZD1; frizzled class receptor 1 [KO:K02432]
8324  
FZD7; frizzled class receptor 7 [KO:K02432]
2535  
FZD2; frizzled class receptor 2 [KO:K02235]
7976  
FZD3; frizzled class receptor 3 [KO:K02329]
8322  
FZD4; frizzled class receptor 4 [KO:K02354]
7855  
FZD5; frizzled class receptor 5 [KO:K02375]
8325  
FZD8; frizzled class receptor 8 [KO:K02375]
8323  
FZD6; frizzled class receptor 6 [KO:K02376]
11211  
FZD10; frizzled class receptor 10 [KO:K02842]
8326  
FZD9; frizzled class receptor 9 [KO:K02842]
4041  
LRP5; low density lipoprotein receptor-related protein 5 [KO:K03068]
4040  
LRP6; low density lipoprotein receptor-related protein 6 [KO:K03068]
25805  
BAMBI; BMP and activin membrane-bound inhibitor [KO:K10162]
1454  
CSNK1E; casein kinase 1, epsilon [KO:K08960] [EC:2.7.11.1]
CSNK1E; LOC400927-CSNK1E readthrough [KO:K08960] [EC:2.7.11.1]
1857  
DVL3; dishevelled segment polarity protein 3 [KO:K02353]
1856  
DVL2; dishevelled segment polarity protein 2 [KO:K02353]
1855  
DVL1; dishevelled segment polarity protein 1 [KO:K02353]
10023  
FRAT1; frequently rearranged in advanced T-cell lymphomas 1 [KO:K03069]
23401  
FRAT2; frequently rearranged in advanced T-cell lymphomas 2 [KO:K03096]
1457  
CSNK2A1; casein kinase 2, alpha 1 polypeptide [KO:K03097] [EC:2.7.11.1]
1459  
CSNK2A2; casein kinase 2, alpha prime polypeptide [KO:K03097] [EC:2.7.11.1]
1460  
CSNK2B; casein kinase 2, beta polypeptide [KO:K03115]
85407  
NKD1; naked cuticle homolog 1 (Drosophila) [KO:K03213]
85409  
NKD2; naked cuticle homolog 2 (Drosophila) [KO:K03213]
80319  
CXXC4; CXXC finger protein 4 [KO:K03344]
59343  
SENP2; SUMO1/sentrin/SMT3 specific peptidase 2 [KO:K03345] [EC:3.4.22.68]
2932  
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
1499  
CTNNB1; catenin (cadherin-associated protein), beta 1, 88kDa [KO:K02105]
8312  
AXIN1; axin 1 [KO:K02157]
8313  
AXIN2; axin 2 [KO:K04385]
324  
APC; adenomatous polyposis coli [KO:K02085]
10297  
APC2; adenomatosis polyposis coli 2 [KO:K02085]
122011  
CSNK1A1L; casein kinase 1, alpha 1-like [KO:K08957] [EC:2.7.11.1]
1452  
CSNK1A1; casein kinase 1, alpha 1 [KO:K08957] [EC:2.7.11.1]
6932  
TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
83439  
TCF7L1; transcription factor 7-like 1 (T-cell specific, HMG-box) [KO:K04490]
6934  
TCF7L2; transcription factor 7-like 2 (T-cell specific, HMG-box) [KO:K04491]
51176  
LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
56998  
CTNNBIP1; catenin, beta interacting protein 1 [KO:K04493]
57680  
CHD8; chromodomain helicase DNA binding protein 8 [KO:K04494] [EC:3.6.4.12]
64321  
SOX17; SRY (sex determining region Y)-box 17 [KO:K04495]
1487  
CTBP1; C-terminal binding protein 1 [KO:K04496]
1488  
CTBP2; C-terminal binding protein 2 [KO:K04496]
1387  
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
8607  
RUVBL1; RuvB-like AAA ATPase 1 [KO:K04499]
4089  
SMAD4; SMAD family member 4 [KO:K04501]
6885  
MAP3K7; mitogen-activated protein kinase kinase kinase 7 [KO:K04427] [EC:2.7.11.25]
51701  
NLK; nemo-like kinase [KO:K04468] [EC:2.7.11.24]
4609  
MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377]
3725  
JUN; jun proto-oncogene [KO:K04448]
8061  
FOSL1; FOS-like antigen 1 [KO:K04502]
595  
CCND1; cyclin D1 [KO:K04503]
894  
CCND2; cyclin D2 [KO:K10151]
896  
CCND3; cyclin D3 [KO:K10152]
5467  
PPARD; peroxisome proliferator-activated receptor delta [KO:K04504]
4316  
MMP7; matrix metallopeptidase 7 (matrilysin, uterine) [KO:K01397] [EC:3.4.24.23]
5663  
PSEN1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
7157  
TP53; tumor protein p53 [KO:K04451]
6477  
SIAH1; siah E3 ubiquitin protein ligase 1 [KO:K04506] [EC:6.3.2.19]
27101  
CACYBP; calcyclin binding protein [KO:K04507]
6500  
SKP1; S-phase kinase-associated protein 1 [KO:K03094]
6907  
TBL1X; transducin (beta)-like 1X-linked [KO:K04508]
90665  
TBL1Y; transducin (beta)-like 1, Y-linked [KO:K04508]
79718  
TBL1XR1; transducin (beta)-like 1 X-linked receptor 1 [KO:K04508]
8945  
BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362]
23291  
FBXW11; F-box and WD repeat domain containing 11 [KO:K03362]
8454  
CUL1; cullin 1 [KO:K03347]
9978  
RBX1; ring-box 1, E3 ubiquitin protein ligase [KO:K03868]
2239  
GPC4; glypican 4 [KO:K08110]
57216  
VANGL2; VANGL planar cell polarity protein 2 [KO:K04510]
81839  
VANGL1; VANGL planar cell polarity protein 1 [KO:K04510]
144165  
PRICKLE1; prickle homolog 1 (Drosophila) [KO:K04511]
166336  
PRICKLE2; prickle homolog 2 (Drosophila) [KO:K04511]
23002  
DAAM1; dishevelled associated activator of morphogenesis 1 [KO:K04512]
23500  
DAAM2; dishevelled associated activator of morphogenesis 2 [KO:K04512]
387  
RHOA; ras homolog family member A [KO:K04513]
9475  
ROCK2; Rho-associated, coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
5880  
RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
5881  
RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
5599  
MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  
MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  
MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
815  
CAMK2A; calcium/calmodulin-dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  
CAMK2D; calcium/calmodulin-dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  
CAMK2B; calcium/calmodulin-dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  
CAMK2G; calcium/calmodulin-dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
5530  
PPP3CA; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
5534  
PPP3R1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
5535  
PPP3R2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
4772  
NFATC1; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 [KO:K04446]
4773  
NFATC2; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 [KO:K17332]
4775  
NFATC3; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3 [KO:K17333]
4776  
NFATC4; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 [KO:K17334]
4088  
SMAD3; SMAD family member 3 [KO:K04500]
Compound
C00076  
Calcium cation
Reference
  Authors
Hatsell S, Rowlands T, Hiremath M, Cowin P.
  Title
Beta-catenin and Tcfs in mammary development and cancer.
  Journal
J Mammary Gland Biol Neoplasia 8:145-58 (2003)
Reference
  Authors
Yang Y.
  Title
Wnts and wing: Wnt signaling in vertebrate limb development and musculoskeletal morphogenesis.
  Journal
Birth Defects Res Part C Embryo Today 69:305-17 (2003)
Reference
  Authors
Kalderon D.
  Title
Similarities between the Hedgehog and Wnt signaling pathways.
  Journal
Trends Cell Biol 12:523-31 (2002)
Reference
  Authors
Nusse R.
  Title
Wnts and Hedgehogs: lipid-modified proteins and similarities in signaling mechanisms at the cell surface.
  Journal
Development 130:5297-305 (2003)
Reference
  Authors
Jope RS, Johnson GV.
  Title
The glamour and gloom of glycogen synthase kinase-3.
  Journal
Trends Biochem Sci 29:95-102 (2004)
Reference
  Authors
Veeman MT, Axelrod JD, Moon RT.
  Title
A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling.
  Journal
Dev Cell 5:367-77 (2003)
Reference
  Authors
Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ, Williams LT.
  Title
PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.
  Journal
Nat Cell Biol 3:628-36 (2001)
Reference
  Authors
Saito-Diaz K, Chen TW, Wang X, Thorne CA, Wallace HA, Page-McCaw A, Lee E
  Title
The way Wnt works: Components and mechanism.
  Journal
Growth Factors 31:1-31 (2013)
Reference
  Authors
Carethers JM
  Title
Intersection of transforming growth factor-beta and Wnt signaling pathways in colorectal cancer and metastasis.
  Journal
Gastroenterology 137:33-6 (2009)
Reference
  Authors
Lin Z, Gao C, Ning Y, He X, Wu W, Chen YG
  Title
The pseudoreceptor BMP and activin membrane-bound inhibitor positively modulates  Wnt/beta-catenin signaling.
  Journal
J Biol Chem 283:33053-8 (2008)
KO pathway
 

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