P56704 (WNT3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein Wnt-3a

Gene names

Name:

WNT3A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	352 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Ligand for members of the frizzled family of seven transmembrane receptors. Wnt-3 and Wnt-3a play distinct roles in cell-cell signaling during morphogenesis of the developing neural tube.
Subunit structure	Homooligomer; disulfide-linked, leading to inactivation By similarity. Interacts with PORCN. Interacts with APCDD1 and WLS. Component of the Wnt-Fzd-LRP5-LRP6 signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly in the complex with LRP6. Ref.6 Ref.7 Ref.9
Subcellular location	Secreted › extracellular space › extracellular matrix.
Tissue specificity	Moderately expressed in placenta and at low levels in adult lung, spleen, and prostate.
Post-translational modification	Palmitoylation at Ser-209 is required for efficient binding to frizzled receptors. It is also required for subsequent palmitoylation at Cys-77. Palmitoylation is required for proper trafficking to cell surface, vacuolar acidification is critical to release palmitoylated WNT3A from WLS in secretory vesicles. Ref.8 Ref.10 Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT3A.
Sequence similarities	Belongs to the Wnt family.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Extracellular matrix Secreted
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway involved in forebrain neuroblast division Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt receptor signaling pathway, calcium modulating pathway Inferred from Biological aspect of Ancestor. Source: RefGenome axis elongation involved in somitogenesis Inferred from electronic annotation. Source: Compara axis specification Inferred from Biological aspect of Ancestor. Source: RefGenome axon guidance Inferred from electronic annotation. Source: Compara axonogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor signaling pathway involved in cardiac muscle cell fate commitment Inferred from direct assay PubMed 20559569. Source: BHF-UCL cell proliferation in forebrain Inferred from sequence or structural similarity. Source: BHF-UCL cell-cell signaling Non-traceable author statement. Source: UniProtKB cellular protein localization Inferred from electronic annotation. Source: Compara cellular response to retinoic acid Inferred from sequence or structural similarity. Source: UniProtKB convergent extension Inferred from Biological aspect of Ancestor. Source: RefGenome determination of left/right symmetry Inferred from Biological aspect of Ancestor. Source: RefGenome dorsal/ventral neural tube patterning Inferred from Biological aspect of Ancestor. Source: RefGenome embryonic pattern specification Inferred from Biological aspect of Ancestor. Source: RefGenome extracellular matrix organization Inferred from Biological aspect of Ancestor. Source: RefGenome heart looping Inferred from electronic annotation. Source: Compara hematopoietic stem cell proliferation Inferred from Biological aspect of Ancestor. Source: RefGenome hippocampus development Inferred from Biological aspect of Ancestor. Source: RefGenome in utero embryonic development Inferred from electronic annotation. Source: Compara inner ear morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome mammary gland development Inferred from Biological aspect of Ancestor. Source: RefGenome midbrain-hindbrain boundary development Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of axon extension involved in axon guidance Inferred from electronic annotation. Source: Compara negative regulation of fat cell differentiation Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of heart induction by canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 19736317. Source: BHF-UCL negative regulation of neurogenesis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of neuron projection development Inferred from sequence or structural similarity. Source: UniProtKB notochord development Inferred from Biological aspect of Ancestor. Source: RefGenome osteoblast differentiation Inferred from electronic annotation. Source: Compara palate development Inferred from mutant phenotype PubMed 18413325. Source: BHF-UCL paraxial mesodermal cell fate commitment Inferred from Biological aspect of Ancestor. Source: RefGenome platelet aggregation Inferred from electronic annotation. Source: Compara positive regulation of B cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 17976063PubMed 18941195. Source: UniProtKB positive regulation of canonical Wnt receptor signaling pathway involved in controlling type B pancreatic cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of cardiac muscle cell differentiation Inferred from direct assay PubMed 20559569. Source: BHF-UCL positive regulation of catenin import into nucleus Inferred from direct assay PubMed 20137080PubMed 20723538. Source: BHF-UCL positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of cell-cell adhesion mediated by cadherin Inferred from electronic annotation. Source: Compara positive regulation of collateral sprouting in absence of injury Inferred from electronic annotation. Source: Compara positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of dermatome development Inferred from direct assay PubMed 10654605. Source: BHF-UCL positive regulation of mesodermal cell fate specification Inferred from direct assay PubMed 20559569. Source: BHF-UCL positive regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 20723538. Source: BHF-UCL positive regulation of protein binding Inferred from direct assay PubMed 16890161. Source: BHF-UCL positive regulation of protein tyrosine kinase activity Inferred from electronic annotation. Source: Compara positive regulation of receptor internalization Inferred from direct assay PubMed 16890161. Source: BHF-UCL positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 20723538. Source: BHF-UCL post-anal tail morphogenesis Inferred from electronic annotation. Source: Compara regulation of microtubule cytoskeleton organization Inferred from electronic annotation. Source: Compara signalosome assembly Inferred from sequence or structural similarity. Source: BHF-UCL skeletal muscle cell differentiation Inferred from electronic annotation. Source: Compara somitogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome spinal cord association neuron differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from sequence or structural similarity. Source: BHF-UCL early endosome Inferred from Biological aspect of Ancestor. Source: RefGenome extracellular space Inferred from sequence or structural similarity. Source: BHF-UCL late endosome Inferred from Biological aspect of Ancestor. Source: RefGenome membrane raft Inferred from Biological aspect of Ancestor. Source: RefGenome plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	extracellular matrix structural constituent Non-traceable author statement. Source: UniProtKB frizzled-2 binding Inferred from Biological aspect of Ancestor. Source: RefGenome receptor agonist activity Inferred from direct assay PubMed 20723538. Source: BHF-UCL transcription coactivator activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FZD8	Q9H461	2	EBI-6173037,EBI-6254212

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 352	334	Protein Wnt-3a		PRO_0000041418
Sites
	Site	34 – 35	2	Cleavage; by TIKI1 and TIKI2 By similarity
Amino acid modifications
	Lipidation	77	1	S-palmitoyl cysteine Ref.10
	Lipidation	209	1	O-palmitoyl serine Ref.8 Ref.10
	Lipidation	209	1	O-palmitoyl serine; by PORCN Ref.8 Ref.10
	Glycosylation	87	1	N-linked (GlcNAc...) Potential
	Glycosylation	298	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	209	1	S → A: Abrogates WLS binding. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P56704 [UniParc]. Last modified May 10, 2002. Version 2. Checksum: A317BD6D4A73920B	FASTA	352	39,365
	10 20 30 40 50 60 MAPLGYFLLL CSLKQALGSY PIWWSLAVGP QYSSLGSQPI LCASIPGLVP KQLRFCRNYV 70 80 90 100 110 120 EIMPSVAEGI KIGIQECQHQ FRGRRWNCTT VHDSLAIFGP VLDKATRESA FVHAIASAGV 130 140 150 160 170 180 AFAVTRSCAE GTAAICGCSS RHQGSPGKGW KWGGCSEDIE FGGMVSREFA DARENRPDAR 190 200 210 220 230 240 SAMNRHNNEA GRQAIASHMH LKCKCHGLSG SCEVKTCWWS QPDFRAIGDF LKDKYDSASE 250 260 270 280 290 300 MVVEKHRESR GWVETLRPRY TYFKVPTERD LVYYEASPNF CEPNPETGSF GTRDRTCNVS 310 320 330 340 350 SHGIDGCDLL CCGRGHNARA ERRREKCRCV FHWCCYVSCQ ECTRVYDVHT CK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of WNT3a and WNT14 clustered in human chromosome 1q42 region." Saitoh T., Hirai M., Katoh M. Biochem. Biophys. Res. Commun. 284:1168-1175(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue." Huguet E.L., McMahon J.A., McMahon A.P., Bicknell R., Harris A.L. Cancer Res. 54:2615-2621(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 207-330. Tissue: Mammary gland.
[6]	"Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells." Baenziger C., Soldini D., Schuett C., Zipperlen P., Hausmann G., Basler K. Cell 125:509-522(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH WLS.
[7]	"Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6." Bourhis E., Tam C., Franke Y., Bazan J.F., Ernst J., Hwang J., Costa M., Cochran A.G., Hannoush R.N. J. Biol. Chem. 285:9172-9179(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRP6 IN THE WNT/FZD/LRP6 COMPLEX.
[8]	"WLS-dependent secretion of WNT3A requires Ser209 acylation and vacuolar acidification." Coombs G.S., Yu J., Canning C.A., Veltri C.A., Covey T.M., Cheong J.K., Utomo V., Banerjee N., Zhang Z.H., Jadulco R.C., Concepcion G.P., Bugni T.S., Harper M.K., Mihalek I., Jones C.M., Ireland C.M., Virshup D.M. J. Cell Sci. 123:3357-3367(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT SER-209 BY PORCN, MUTAGENESIS OF SER-209.
[9]	"APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex." Shimomura Y., Agalliu D., Vonica A., Luria V., Wajid M., Baumer A., Belli S., Petukhova L., Schinzel A., Brivanlou A.H., Barres B.A., Christiano A.M. Nature 464:1043-1047(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH APCDD1.
[10]	"Fatty acid modification of Wnt1 and Wnt3a at serine is prerequisite for lipidation at cysteine and is essential for Wnt signalling." Doubravska L., Krausova M., Gradl D., Vojtechova M., Tumova L., Lukas J., Valenta T., Pospichalova V., Fafilek B., Plachy J., Sebesta O., Korinek V. Cell. Signal. 23:837-848(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-77 AND SER-209.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB060284 mRNA. Translation: BAB61052.1. AK056278 mRNA. Translation: BAB71136.1. AL136379 Genomic DNA. Translation: CAI23122.1. BC103922 mRNA. Translation: AAI03923.1.
IPI	IPI00654606.
RefSeq	NP_149122.1. NM_033131.3.
UniGene	Hs.336930.
3D structure databases
ProteinModelPortal	P56704.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-58592N.
IntAct	P56704. 3 interactions.
STRING	9606.ENSP00000284523.
PTM databases
PhosphoSite	P56704.
Polymorphism databases
DMDM	20532424.
Proteomic databases
PaxDb	P56704.
PRIDE	P56704.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000284523; ENSP00000284523; ENSG00000154342.
GeneID	89780.
KEGG	hsa:89780.
UCSC	uc001hrq.2. human.
Organism-specific databases
CTD	89780.
GeneCards	GC01P228194.
HGNC	HGNC:15983. WNT3A.
HPA	HPA050514.
MIM	606359. gene.
neXtProt	NX_P56704.
PharmGKB	PA38074.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG284879.
HOGENOM	HOG000039529.
HOVERGEN	HBG001595.
InParanoid	P56704.
KO	K00312.
OrthoDB	EOG4XD3R9.
PhylomeDB	P56704.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	P56704.
Bgee	P56704.
CleanEx	HS_WNT3A.
Genevestigator	P56704.
Family and domain databases
InterPro	IPR005817. Wnt. IPR009141. Wnt3. IPR018161. Wnt_CS. [Graphical view]
PANTHER	PTHR12027. PTHR12027. 1 hit. PTHR12027:SF18. PTHR12027:SF18. 1 hit.
Pfam	PF00110. wnt. 1 hit. [Graphical view]
PRINTS	PR01843. WNT3PROTEIN. PR01349. WNTPROTEIN.
SMART	SM00097. WNT1. 1 hit. [Graphical view]
PROSITE	PS00246. WNT1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P56704.
ChEMBL	CHEMBL1255137.
GenomeRNAi	89780.
NextBio	76263.
SOURCE	Search...

Entry information

Entry name

WNT3A_HUMAN

Accession

Primary (citable) accession number: P56704
Secondary accession number(s): Q3SY80, Q969P2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 10, 2002
Last modified:	May 1, 2013
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.