Wnt signaling Pathway (Archived)
Varsha Khodiyar, Suzi Lewis
Justification (Impact and significance)
Wnt proteins form a family of highly conserved secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis. Insights into the mechanisms of Wnt action have emerged from several systems: genetics in Drosophila and Caenorhabditis elegans; biochemistry in cell culture and ectopic gene expression in Xenopus embryos. Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling. As currently understood, Wnt proteins bind to receptors of the Frizzled and LRP families on the cell surface. Through several cytoplasmic relay components, the signal is transduced to beta-catenin, which enters the nucleus and forms a complex with TCF to activate transcription of Wnt target gene (text from 
Range of species in which the pathway is found
Each reference genome species is represented in at least 1 of the panther families, except for E.coli which has no gene products in any of these families.
Species experimentally studied
Professor Roel Nusse, Howard Hughes Medical Institute 
Dr Nobue Itasaki, National Institute for Medical Research, UCL 
Time frame of the project
- June - August 2010: Primary annotations
- November - December 2010: Tree Annotation
- http://www.stanford.edu/~rnusse/wntwindow.html (note that there are some errors in their phylogenetic trees)
- A useful graphic with descriptive text: http://www.sabiosciences.com/pathway.php?sn=WNT_Signaling
Families to annotate (BATCH 1)
- Pascale and Paul have reviewed the trees, and there are no obvious problems
Summary of trees 
- PTHR12027 wnt: 6 distinct subfamilies
- Secreted signalling proteins, implicated in regulation of cell fate and patterning during embryogenesis.
- PTHR23315: beta-catenin and the subtree to which beta-catenin belongs seems okay
- PTHR10845:AN318: Axin
- Subfamily of the RGS (Regulators of G-protein signaling)
- PTHR11309 frizzled: 7 distinct subfamilies
- Transmembrane proteins that are receptors for the Wnt signaling proteins.
- Proteins that are related to the frizzled protein family in that they also contain the Wnt-binding site, but SFRP family are secreted and not membrane bound. We will include these as they are in the same family
- PTHR10878: Disheveled
- Cytoplasmic phosphoproteins, role in cytoplasmic signal transduction of Wnt signaling pathway. Regulation of beta-catenin stability.
- PTHR10529: LRP
- Probable co-receptor together with Frizzled for Wnt. Rather large family, so only annotating LRP5 and LRP6 for this project.
- PTHR12607 ADENOMATOUS POLYPOSIS COLI PROTEIN
- Intracellular cytoskeleton, role in structure of adherens junction. Negative regulator of Wnt signaling, degrades CTNNB1
- PTHR10373 LYMPHOID ENHANCER-BINDING FACTOR 1
- Participates in the Wnt signaling pathway. Activates transcription of target genes in the presence of CTNNB1 and EP300.
Annotation targets/progress table (BATCH 1)
Note that the panther subfamilies can be accessed by searching the Panther website: http://www.pantherdb.org/
or directly using the following example URL:
|Active annotation period (Dates)||Panther Family||Gene Symbol (Human protein ID)||PAINT due to begin||GOA / BHF-UCL||MGI||RGD||ZFIN||Wormbase||Flybase||Agbase||Dictybase||TAIR||SGD||Pombase|
|Week 1-2 (1st-16th July)||PTHR12027:SF15, PTHR12027:SF18, PTHR12027:SF25||wnt1 (P04628) wnt3 (P56703)||Week 5||8th July [VK]||done||done||done||none||none||none||none||none|
|PTHR12027:SF21, PTHR12027:SF23||wnt2 (P09544) wnt5 (P41221, Q9H1J7)||Week 5||14th July [RL,RH]||done||done||done||none||none||none||none||none||none|
|PTHR12027:SF4, PTHR12027:SF6, PTHR12027:SF7, PTHR12027:SF19||wnt4 (P56705) wnt8 (Q9H1J5, Q93098) wnt9 (O14904, O14905) wnt11 (O96014)||Week 5||15th July [VK,YAF]||done||done||done||none||none||none||none||none|
|PTHR12027:SF14||wnt6 (Q9Y6F9)||Week 5||9th July [RL]||done||done||done||none||done||none||none||none||none|
|PTHR12027:SF16, PTHR12027:SF22, PTHR12027:SF26||wnt7 (O00755, P56706) wnt16 (Q9UBV4)||Week 5||13th July [RL,YAF]||done||done||done||none||none||none||none||none||none|
|PTHR12027:SF11||wnt10 (WNT10A Q9GZT5, WNT10B O00744)||Week 5||2nd July [RL]||done||done||done||none||done||none||none||none||none|
|Week 3 (17th-23rd July)||PTHR23315||CTNNB1 (P35222)||Week 7||22nd July [VK]||done||done||done||done||done||none||done||done||30th June [VW]|
|PTHR16505||CTNNBIP1 (Q9NSA3)||Week 7||22nd July [RL]||done||done||done||done||none||none||none||none||none|
|Week 4 (24th-31st July)||PTHR10845:SF11||Axin1 (O15169)||Week 8||30th July [RL]||done||done||none||no EXP data||none||none||30th June [VW]|
|PTHR10845:SF103||Axin2 (Q9Y2T1)||Week 8||28th July [VK]||done||done||none||no EXP data||none(At gene is in SF44, did that one)||none||30th June [VW]|
|Week 5-6 (1st-13th August)||PTHR11309:SF31, PTHR11309:SF32, PTHR11309:SF33, PTHR11309:SF34, PTHR11309:SF49||fzd1 (Q9UP38) fzd2 (Q14332) fzd7 (O75084)||Week 9||10 Aug [RL]||done||done||none||none||none||none||none|
|PTHR11309:SF28, PTHR11309:SF29||fzd5 (Q13467) fzd8 (Q9H461)||Week 9||done||done||none||none||none||none||none|
|PTHR11309:SF23||fzd4 (Q9ULV1)||Week 9||10th Aug [RL]||done||done||none||none||none||none||none|
|PTHR11309:SF24||fzd10 (Q9ULW2)||Week 9||6th Aug [RL]||done||done||done||none||none||none||none||none|
|PTHR11309:SF25||fzd9 (O00144) fzd3 (Q9NPG1)||Week 9||18th Aug [VK]||done||done||none||none||none||none||none||none|
|PTHR11309:SF21||fzd6 (O60353)||Week 9||28th July [VK]||done||done||none||none||none||none||none|
|Week 6-7 (14th-20th August)||PTHR11309:SF7, PTHR11309:SF10||SFRP1 (Q8N474) SFRP2 (Q96HF1) SFRP4 (Q6FHJ7)||Week 10||done||done||none||none||none||none||none|
|PTHR11309:SF10||SFRP5 (Q5T4F7)||Week 10||15 Aug [RL]||done||done||none||none||none||none||none|
|Week 8 (21st-31st August)||PTHR10878||dvl1 (O14640) dvl2 (O14641) dvl3 (Q92997)||Week 11||done||done||none||none||none||none|
|Week 9-10 (1st-10th September)||PTHR10529:SF108||LRP5 (O75197)||Week 13||done||done||no EXP data||none||none||none|
|PTHR10529:SF109||LRP6 (O75581)||Week 13||done||done||no EXP data||none||none||none|
|Week 11 (11th-17th September)||PTHR12607||APC (P25054) APC2 (O95996)||Week 14||none||none||none||none||none||none|
|PTHR10373:SF11||LEF1 (Q9UJU2)||Week 15||none||none||none||none|
|Week 12-16 (18th September - 22nd October)||Review annotations with respect to PAINT inferences)|
The aim is to provide good annotation coverage for these Panther families across the 11 species in a 3-month time frame, followed by a 2-week period of annotation review in response to PAINT inferences.
- Each family is annotated in the order listed above, for a maximum of 2 weeks.
- The priority is to annotate the gene products listed above, and orthologs in all species. Where the subfamily is shown, this means that the Panther family is very large and so MODs are asked to focus on the specific subfamilies shown. MODs are free to annotate to members of the larger family if they have time and wish to do so.
- We are asking MODs to sign off each line of this table, so we can confirm that the whole clade has been annotated across all species.
- PAINT curation will take place using as many annotations as available for each species, at the end of the specified annotation 2-week period. At this point they will deposit a GAF file in the CVS repository . It is only necessary that the annotations for the proteins/genes worked on in this period be provided.
- PAINT inferences will begin to be sent back to MODs for checking as soon as they have been completed. We have allowed 2 weeks at the end of the annotation period for PAINT inference checking; however, MODs will be able to check the inferences earlier than this if they wish.
Other families to annotate (Prioritization TBD)
- PTHR10878:SF4 DIXIN (DIX DOMAIN-CONTAINING PROTEIN 1)(COILED-COIL PROTEIN DIX1)
- dixdc1 (Q80Y83)
- PTHR22844:SF10 F-BOX AND WD-40 DOMAIN PROTEIN
- BTRC (Q9Y297) Mediates the ubiquitination of CTNNB1 and participates in Wnt signaling
- FBXW11 (Q9UKB1) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling
- PTHR13164:SF3 Ubiquitin-mediated degradation of beta-catenin (CTNNB1)
- CACYBP (Q9HB71)
- PTHR12011:SF67 and PTHR25100:SF76 CALCITONIN RECEPTOR
- CALCR (P30988)
- PTHR24347:SF64: long-term potentiation and neurotransmitter release
- CAMK2A (Q9UQM7)
- CAMK2B (Q13554)
- CAMK2D (Q13557)
- CAMK2G (Q13555)
- PTHR12015:SF30 SMALL INDUCIBLE CYTOKINE A
- CCL2 P13500
- PTHR10177:SF67 G1/S-SPECIFIC CYCLIN-D1
- CCND1 (P24385)
- CCND2 (P30279)
- CCND3 (P30281)
- CER1 (O95813)
- PTHR10799:SF46 CHROMODOMAIN-HELICASE-DNA-BINDING PROTEIN 8 (CHD-8)
- CHD8 (Q9HCK8) negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity
- CHEK2 (O96017)
- PTHR23056:SF4 CALCINEURIN B SUBUNIT
- CHP (Q99653)
- CHP2 (O43745)
- PPP3R1 P63098
- PPP3R2 Q96LZ3
- COL1A1 (P02452)
- COL1A2 (P08123)
- CREBBP (Q92793) part of canonical Wnt pathway
- EP300 (Q09472)
- CSNK1A1 (P48729) Participates in Wnt signaling
- CSNK1A1L (Q8N752) Participates in Wnt signaling
- CSNK1E (P49674) Participates in Wnt signaling
- CSNK2A1 (P68400) Participates in Wnt signaling
- CSNK2A2 (P19784) Participates in Wnt signaling
- CSNK2B (P67870) Participates in Wnt signaling
- PTHR10996:SF11 C-TERMINAL-BINDING PROTEIN 1
- CTBP1 (Q13363) Canonical Wnt signaling pathway.
- CTBP2 (P56545)
- PTHR11932:SF19 CULLIN 1
- CUL1 (Q13616) direct ubiquitination of CTNNB1 and participate in Wnt signaling
- CXXC4 (Q9H2H0) negative regulator of the Wnt signaling pathway via its interaction with DVL1
- DAAM1 (Q9Y4D1) mediates Wnt-induced Dvl-Rho complex formation
- DAAM2 (Q86T65)
- PTHR10568:SF4 DICKKOPF-RELATED PROTEIN 1
- DKK1 (O94907) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
- DKK2 (Q9UBU2) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
- DKK4 (Q9UBP4) Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt
- PTHR11371:SF7 DEOXYRIBONUCLEASE I
- DNASE1 (P24855)
- PTHR23351 FOS-RELATED ANTIGEN 1
- FOSL1 (P15407)
- FRAT1 (Q92837) Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3
- FRAT2 (O75474) Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3.
- GSK3B (P49841) Participates in the Wnt signaling pathway.
- PTHR10082 INTEGRIN BETA-3
- ITGB3 (P05106)
- PTHR11462 TRANSCRIPTION FACTOR C-JUN
- JUN (P05412) Presenilin action in Notch and Wnt signaling.
- MAP3K7 O43318 Noncanonical Wnt signaling pathway.
- MAPK10 P53779
- MAPK8 P45983
- MAPK9 P45984
- PTHR11501 MICROTUBULE-ASSOCIATED PROTEIN TAU
- MAPT P10636
- PTHR10201 MATRILYSIN
- MMP7 P09237
- PTHR11514 MYC PROTO-ONCOGENE PROTEIN
- MYC P01106 Canonical Wnt signaling pathway.
- NFAT5 O94916
- NFATC1 O95644
- NFATC2 Q13469 Noncanonical Wnt signaling pathway.
- NFATC3 Q12968
- NFATC4 Q14934
- NKD1 Q969G9 Cell autonomous antagonist of the canonical Wnt signaling pathway.
- NKD2 Q969F2 Cell autonomous antagonist of the canonical Wnt signaling pathway.
- NLK Q9UBE8 Acts downstream of MAP3K7 and HIPK2 to negatively regulate the canonical Wnt/beta-catenin signaling pathway
- PDLIM4 P50479
- PTHR10336 1-PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE PHOSPHODIESTERASE BETA-1
- PLCB1 Q9NQ66
- PLCB2 Q00722
- PLCB3 Q01970
- PLCB4 Q15147
- PTHR13906 PORCUPINE
- PORCN Q9H237 Modulates the processing of Wnt proteins.
- PPARD Q03181 Presenilin action in Notch and Wnt signaling.
- VDR P11473
- PTHR11668 SERINE/THREONINE PROTEIN PHOSPHATASE PP2A
- PPP2CA P67775 Regulation of Wnt receptor signaling pathway
- PPP2CB P62714 Signaling by Wnt.
- PPP3CA Q08209
- PPP3CB P16298
- PPP3CC P48454
- PTHR10648 SERINE/THREONINE-PROTEIN PHOSPHATASE 2A 65 KDA REGULATORY SUBUNIT A ALPHA ISOFORM
- PPP2R1A P30153 regulation of Wnt receptor signaling pathway
- PPP2R1B P30154 Signaling by Wnt.
- PTHR10257 SERINE/THREONINE-PROTEIN PHOSPHATASE 2A 56 KDA REGULATORY SUBUNIT ALPHA ISOFORM
- PPP2R5A Q15172 Signaling by Wnt.
- PPP2R5B Q15173 Signaling by Wnt.
- PPP2R5C Q13362 Signaling by Wnt.
- PPP2R5D Q14738 Canonical Wnt signaling pathway.
- PPP2R5E Q16537
- PRICKLE1 Q96MT3
- PRICKLE2 Q7Z3G6
- PRKACA P17612
- PRKACB P22694
- PRKACG P22612
- RPS6KA3 Q7Z2J4
- PRKCA P17252
- PRKCB P05771
- PRKCG P05129
- PRKX P51817
- PTHR10202:SF7 PRESENILIN-1 *Former RefGenome target
- PSEN1 P49768 increases the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling
- PTHR11599 PROTEASOME SUBUNIT ALPHA TYPE 1
- PSMA1 P25786 Signaling by Wnt.
- PSMA2 P25787 Signaling by Wnt.
- PSMA3 P25788 Signaling by Wnt.
- PSMA4 P25789 Signaling by Wnt.
- PSMA5 P28066 Signaling by Wnt.
- PSMA6 P60900 Signaling by Wnt.
- PSMA7 O14818 Signaling by Wnt.
- PSMB1 P20618 Signaling by Wnt.
- PSMB10 P40306 Signaling by Wnt.
- PSMB2 P49721 Signaling by Wnt.
- PSMB3 P49720 Signaling by Wnt.
- PSMB4 P28070 Signaling by Wnt.
- PSMB5 P28074 Signaling by Wnt.
- PSMB6 P28072 Signaling by Wnt.
- PSMB7 Q99436 Signaling by Wnt.
- PSMB8 P28062 Signaling by Wnt.
- PSMB9 P28065 Signaling by Wnt.
- PTHR23073 26S PROTEASE REGULATORY SUBUNIT 4
- PSMC1 P62191 Signaling by Wnt.
- PSMC2 P35998 Signaling by Wnt.
- PSMC3 P17980 Signaling by Wnt.
- PSMC4 P43686 Signaling by Wnt.
- PSMC5 P62195 Signaling by Wnt.
- PSMC6 P62333 Signaling by Wnt.
- PTHR10943 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 1
- PSMD1 Q99460 Signaling by Wnt.
- PSMD10 O75832 Signaling by Wnt.
- PTHR10678 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 11
- PSMD11 O00231 Signaling by Wnt.
- PTHR10855 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 12
- PSMD12 O00232 Signaling by Wnt.
- PTHR10539 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 13
- PSMD13 Q9UNM6 Signaling by Wnt.
- PTHR10410 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 14
- PSMD14 O00487 Signaling by Wnt.
- PTHR10943 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 2
- PSMD2 Q13200 Signaling by Wnt.
- PTHR10758 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 3
- PSMD3 O43242 Signaling by Wnt.
- PTHR10223 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 4
- PSMD4 P55036 Signaling by Wnt.
- PTHR13554 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 5
- PSMD5 Q16401 Signaling by Wnt.
- PTHR14145 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 6
- PSMD6 Q15008 Signaling by Wnt.
- PTHR10540 26S PROTEASOME NON-ATPASE REGULATORY SUBUNIT 7
- PSMD7 P51665 Signaling by Wnt.
- PSMD8 P48556 Signaling by Wnt.
- PSMD9 O00233 Signaling by Wnt.
- PTHR10660 PROTEASOME ACTIVATOR COMPLEX SUBUNIT 1
- PSME1 Q06323 Signaling by Wnt.
- PSME2 Q9UL46 Signaling by Wnt.
- PSME3 P61289 Signaling by Wnt.
- PSMF1 Q92530 Signaling by Wnt.
- PTHR19134 PROTEIN TYROSINE PHOSPHATASE N11 (SHP2)
- PTPN11 Q06124
- RAC1 P63000
- RAC2 P15153
- RAC3 P60763
- RHOA P61586
- PTHR13742 RETINOBLASTOMA-ASSOCIATED PROTEIN
- RB1 P06400
- PTHR11210:SF2 RING FINGER 1
- RBX1 P62877
- PTHR22988 RHO-ASSOCIATED, COILED-COIL CONTAINING PROTEIN KINASE
- ROCK1 Q13464
- ROCK2 O75116
- PTHR10666 UBIQUITIN (RIBOSOMAL PROTEIN L40)
- RPS27A P62988 Signaling by Wnt.
- RUVBL1 Q9Y265
- SENP2 Q9HC62 down-regulate CTNNB1 levels and thereby modulate the Wnt pathway
- PTHR11165 SKP1-RELATED
- SKP1 P63208 Signaling by Wnt.
- PTHR13703 SMAD
- SMAD1 Q15797
- SMAD2 Q15796
- SMAD3 P84022
- SMAD4 Q13485 Canonical Wnt signaling pathway.
- PTHR23113 RAS GTP EXCHANGE FACTOR, SON OF SEVENLESS
- SOS1 Q07889
- PTHR10270 TRANSCRIPTION FACTOR SOX-17
- SOX17 Q9H6I2 negative regulation of Wnt receptor signaling pathway through beta-catenin
- PTHR11267 BRACHYURY
- T O15178
- PTHR22846 TRANSDUCIN BETA-LIKE 1
- TBL1X O60907 Wnt receptor signaling pathway through beta-catenin
- TBL1XR1 Q9BZK7 Wnt receptor signaling pathway through beta-catenin
- TBL1Y Q9BQ87
- PTHR10373 TRANSCRIPTION FACTOR 7
- TCF7 P36402 Wnt signaling pathway
- TCF7L1 Q9HCS4 Participates in the Wnt signaling pathway.
- TCF7L2 Q9NQB0 Participates in the Wnt signaling pathway
- PTHR11447 CELLULAR TUMOR ANTIGEN P53 *Former RefGenome target
- TP53 P04637
- PTHR11371:SF7 DEOXYRIBONUCLEASE I
- TRAP1 P24855
- VANGL1 Q8TAA9
- VANGL2 Q9ULK5
- VHL P40337
- WIF1 Q9Y5W5 Binds to WNT proteins and inhibits their activities.