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KEGG   PATHWAY: hsa04310
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
Pathway map
hsa04310  Wnt signaling pathway
hsa04310

Network
  Element
N00056  Wnt signaling pathway
N01427  WNT5A-ROR signaling pathway
N01440  Wnt signaling modulation, LGR/RSPO
N01441  Wnt signaling modulation, SOST/LRP4
N01442  Wnt signaling modulation, Wnt inhibitor
N01443  Wnt signaling modulation, Wnt acylation
Drug
D10094  Blosozumab (USAN)
D10156  Romosozumab (USAN)
D10410  Vantictumab (USAN/INN)
D11322  Umbralisib (USAN/INN)
D11323  Umbralisib tosylate (USAN)
D11369  Rosmantuzumab (USAN)
D11758  Ipafricept (USAN/INN)
D12209  Ozuriftamab (USAN)
D12210  Ozuriftmab vedotin (USAN)
D12235  Osugacestat (USAN/INN)
D12416  Petosemtamab (USAN/INN)
D12445  Foscenvivint (JAN/INN)
Other DBs
GO: 0016055
Organism
Homo sapiens (human) [GN:hsa]
Gene
64840  PORCN; porcupine O-acyltransferase [KO:K00181] [EC:2.3.1.250]
7471  WNT1; Wnt family member 1 [KO:K03209]
7472  WNT2; Wnt family member 2 [KO:K00182]
7482  WNT2B; Wnt family member 2B [KO:K00182]
7473  WNT3; Wnt family member 3 [KO:K00312]
89780  WNT3A; Wnt family member 3A [KO:K00312]
54361  WNT4; Wnt family member 4 [KO:K00408]
7474  WNT5A; Wnt family member 5A [KO:K00444]
81029  WNT5B; Wnt family member 5B [KO:K00444]
7475  WNT6; Wnt family member 6 [KO:K00445]
7476  WNT7A; Wnt family member 7A [KO:K00572]
7477  WNT7B; Wnt family member 7B [KO:K00572]
7478  WNT8A; Wnt family member 8A [KO:K00714]
7479  WNT8B; Wnt family member 8B [KO:K00714]
7483  WNT9A; Wnt family member 9A [KO:K01064]
7484  WNT9B; Wnt family member 9B [KO:K01064]
7480  WNT10B; Wnt family member 10B [KO:K01357]
80326  WNT10A; Wnt family member 10A [KO:K01357]
7481  WNT11; Wnt family member 11 [KO:K01384]
51384  WNT16; Wnt family member 16 [KO:K01558]
9350  CER1; cerberus 1, DAN family BMP antagonist [KO:K01645]
147111  NOTUM; notum, palmitoleoyl-protein carboxylesterase [KO:K19882] [EC:3.1.1.98]
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]
5176  SERPINF1; serpin family F member 1 [KO:K19614]
6422  SFRP1; secreted frizzled related protein 1 [KO:K02166]
6423  SFRP2; secreted frizzled related protein 2 [KO:K02176]
2487  FRZB; frizzled related protein [KO:K25481]
6424  SFRP4; secreted frizzled related protein 4 [KO:K02185]
6425  SFRP5; secreted frizzled related protein 5 [KO:K02222]
284654  RSPO1; R-spondin 1 [KO:K19471]
340419  RSPO2; R-spondin 2 [KO:K23097]
84870  RSPO3; R-spondin 3 [KO:K23098]
343637  RSPO4; R-spondin 4 [KO:K23099]
55366  LGR4; leucine rich repeat containing G protein-coupled receptor 4 [KO:K04309]
8549  LGR5; leucine rich repeat containing G protein-coupled receptor 5 [KO:K04308]
59352  LGR6; leucine rich repeat containing G protein-coupled receptor 6 [KO:K08399]
54894  RNF43; ring finger protein 43 [KO:K15694] [EC:2.3.2.27]
84133  ZNRF3; zinc and ring finger 3 [KO:K16273] [EC:2.3.2.27]
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; LDL receptor related protein 5 [KO:K03068]
4040  LRP6; LDL receptor related protein 6 [KO:K03068]
25805  BAMBI; BMP and activin membrane bound inhibitor [KO:K10162]
147495  APCDD1; APC down-regulated 1 [KO:K25812]
164284  APCDD1L; APC down-regulated 1 like [KO:K25812]
1454  CSNK1E; casein kinase 1 epsilon [KO:K08960] [EC:2.7.11.1]
102800317  TPTEP2-CSNK1E; TPTEP2-CSNK1E readthrough [KO:K08960] [EC:2.7.11.1]
440193  CCDC88C; coiled-coil domain containing 88C [KO:K25811]
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; FRAT regulator of WNT signaling pathway 1 [KO:K03069]
23401  FRAT2; FRAT regulator of WNT signaling pathway 2 [KO:K03096]
1457  CSNK2A1; casein kinase 2 alpha 1 [KO:K03097] [EC:2.7.11.1]
1459  CSNK2A2; casein kinase 2 alpha 2 [KO:K03097] [EC:2.7.11.1]
283106  CSNK2A3; casein kinase 2 alpha 3 [KO:K03097] [EC:2.7.11.1]
1460  CSNK2B; casein kinase 2 beta [KO:K03115]
85407  NKD1; NKD inhibitor of WNT signaling pathway 1 [KO:K03213]
85409  NKD2; NKD inhibitor of WNT signaling pathway 2 [KO:K03213]
80319  CXXC4; CXXC finger protein 4 [KO:K03344]
59343  SENP2; SUMO 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 beta 1 [KO:K02105]
8312  AXIN1; axin 1 [KO:K02157]
8313  AXIN2; axin 2 [KO:K04385]
324  APC; APC regulator of WNT signaling pathway [KO:K02085]
10297  APC2; APC regulator of WNT signaling pathway 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 [KO:K02620]
83439  TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
84445  LZTS2; leucine zipper tumor suppressor 2 [KO:K26471]
56998  CTNNBIP1; catenin beta interacting protein 1 [KO:K04493]
25776  CBY1; chibby 1, beta catenin antagonist [KO:K23402]
57680  CHD8; chromodomain helicase DNA binding protein 8 [KO:K04494] [EC:5.6.2.-]
4163  MCC; MCC regulator of WNT signaling pathway [KO:K26734]
57805  CCAR2; cell cycle and apoptosis regulator 2 [KO:K25816]
23411  SIRT1; sirtuin 1 [KO:K11411] [EC:2.3.1.286]
64321  SOX17; SRY-box transcription factor 17 [KO:K04495]
1487  CTBP1; C-terminal binding protein 1 [KO:K04496] [EC:1.1.1.428]
1488  CTBP2; C-terminal binding protein 2 [KO:K04496] [EC:1.1.1.428]
102723796  TLE7; TLE family member 7 [KO:K04497]
7088  TLE1; TLE family member 1, transcriptional corepressor [KO:K04497]
7089  TLE2; TLE family member 2, transcriptional corepressor [KO:K04497]
7090  TLE3; TLE family member 3, transcriptional corepressor [KO:K04497]
7091  TLE4; TLE family member 4, transcriptional corepressor [KO:K04497]
79816  TLE6; TLE family member 6, subcortical maternal complex member [KO:K04497]
1501  CTNND2; catenin delta 2 [KO:K23491]
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] [EC:5.6.2.4]
4089  SMAD4; SMAD family member 4 [KO:K04501]
4088  SMAD3; SMAD family member 3 [KO:K23605]
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; MYC proto-oncogene, bHLH transcription factor [KO:K04377]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
8061  FOSL1; FOS like 1, AP-1 transcription factor subunit [KO:K04502]
595  CCND1; cyclin D1 [KO:K04503]
894  CCND2; cyclin D2 [KO:K10151]
896  CCND3; cyclin D3 [KO:K10152]
8840  CCN4; cellular communication network factor 4 [KO:K22471]
5467  PPARD; peroxisome proliferator activated receptor delta [KO:K04504]
4316  MMP7; matrix metallopeptidase 7 [KO:K01397] [EC:3.4.24.23]
5663  PSEN1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
5566  PRKACA; protein kinase cAMP-activated catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
5567  PRKACB; protein kinase cAMP-activated catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
5568  PRKACG; protein kinase cAMP-activated catalytic subunit gamma [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:2.3.2.27]
27101  CACYBP; calcyclin binding protein [KO:K04507]
6500  SKP1; S-phase kinase associated protein 1 [KO:K03094]
6907  TBL1X; transducin beta like 1 X-linked [KO:K04508]
90665  TBL1Y; transducin beta like 1 Y-linked [KO:K04508]
79718  TBL1XR1; TBL1X/Y related 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 [KO:K03868] [EC:2.3.2.32]
2239  GPC4; glypican 4 [KO:K08110]
4919  ROR1; receptor tyrosine kinase like orphan receptor 1 [KO:K05122] [EC:2.7.10.1]
4920  ROR2; receptor tyrosine kinase like orphan receptor 2 [KO:K05123] [EC:2.7.10.1]
6259  RYK; receptor like tyrosine kinase [KO:K05128] [EC:2.7.10.1]
57216  VANGL2; VANGL planar cell polarity protein 2 [KO:K04510]
81839  VANGL1; VANGL planar cell polarity protein 1 [KO:K04510]
144165  PRICKLE1; prickle planar cell polarity protein 1 [KO:K04511]
166336  PRICKLE2; prickle planar cell polarity protein 2 [KO:K04511]
29964  PRICKLE4; prickle planar cell polarity protein 4 [KO:K04511]
4007  PRICKLE3; prickle planar cell polarity protein 3 [KO:K04511]
27130  INVS; inversin [KO:K19626]
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:2.7.11.39]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
5880  RAC2; Rac family small GTPase 2 [KO:K07860]
5881  RAC3; Rac family small GTPase 3 [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 [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 [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 [KO:K04348] [EC:3.1.3.16]
5532  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  PPP3CC; protein phosphatase 3 catalytic subunit gamma [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:K19662] [EC:2.7.11.13]
5582  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
4772  NFATC1; nuclear factor of activated T cells 1 [KO:K04446]
4773  NFATC2; nuclear factor of activated T cells 2 [KO:K17332]
4775  NFATC3; nuclear factor of activated T cells 3 [KO:K17333]
4776  NFATC4; nuclear factor of activated T cells 4 [KO:K17334]
Compound
C00076  Calcium cation
Reference
PMID:14635791
  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)
DOI:10.1023/A:1025944723047
Reference
PMID:14745971
  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)
DOI:10.1002/bdrc.10026
Reference
PMID:12446114
  Authors
Kalderon D.
  Title
Similarities between the Hedgehog and Wnt signaling pathways.
  Journal
Trends Cell Biol 12:523-31 (2002)
DOI:10.1016/S0962-8924(02)02388-7
Reference
PMID:14530294
  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)
DOI:10.1242/dev.00821
Reference
PMID:15102436
  Authors
Jope RS, Johnson GV.
  Title
The glamour and gloom of glycogen synthase kinase-3.
  Journal
Trends Biochem Sci 29:95-102 (2004)
DOI:10.1016/j.tibs.2003.12.004
Reference
PMID:12967557
  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)
DOI:10.1016/S1534-5807(03)00266-1
Reference
PMID:11433294
  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)
DOI:10.1038/35083016
Reference
PMID:23256519
  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)
DOI:10.3109/08977194.2012.752737
Reference
PMID:19482104
  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)
DOI:10.1053/j.gastro.2009.05.011
Reference
PMID:18838381
  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)
DOI:10.1074/jbc.M804039200
Reference
PMID:23151663
  Authors
Niehrs C
  Title
The complex world of WNT receptor signalling.
  Journal
Nat Rev Mol Cell Biol 13:767-79 (2012)
DOI:10.1038/nrm3470
Reference
PMID:28522145
  Authors
Abou Ziki MD, Mani A
  Title
Wnt signaling, a novel pathway regulating blood pressure? State of the art review.
  Journal
Atherosclerosis 262:171-178 (2017)
DOI:10.1016/j.atherosclerosis.2017.05.001
Reference
PMID:25808920
  Authors
He Y, Ki H, Kim H, Kim K
  Title
delta-Catenin interacts with LEF-1 and negatively regulates its transcriptional activity.
  Journal
Cell Biol Int 39:954-61 (2015)
DOI:10.1002/cbin.10465
Reference
PMID:32888647
  Authors
Esaki N, Enomoto A, Takagishi M, Mizutani Y, Iida T, Ushida K, Shiraki Y, Mii S, Takahashi M
  Title
The Daple-CK1epsilon complex regulates Dvl2 phosphorylation and canonical Wnt signaling.
  Journal
Biochem Biophys Res Commun 532:406-413 (2020)
DOI:10.1016/j.bbrc.2020.08.066
Reference
PMID:28242765
  Authors
Yiew NKH, Chatterjee TK, Tang YL, Pellenberg R, Stansfield BK, Bagi Z, Fulton DJ, Stepp DW, Chen W, Patel V, Kamath VM, Litwin SE, Hui DY, Rudich SM, Kim HW, Weintraub NL
  Title
A novel role for the Wnt inhibitor APCDD1 in adipocyte differentiation: Implications for diet-induced obesity.
  Journal
J Biol Chem 292:6312-6324 (2017)
DOI:10.1074/jbc.M116.758078
Related
pathway
hsa04010  MAPK signaling pathway
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04120  Ubiquitin mediated proteolysis
hsa04350  TGF-beta signaling pathway
hsa04510  Focal adhesion
hsa04520  Adherens junction
hsa05010  Alzheimer disease
KO pathway
ko04310   

  All links  
Network (6)   
   KEGG NETWORK (6)   
Genome (1)   
   KEGG GENOME (1)   
Gene (174)   
   KEGG GENES (174)   
All databases (181)   

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