Reviewed, UniProtKB/Swiss-Prot P41221 (WNT5A_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein Wnt-5a

Gene names

Name:

WNT5A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	380 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. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression. Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor. Mediates motility of melanoma cells. Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle. Inhibits type II collagen expression in chondrocytes. Ref.5 Ref.6
Subunit structure	Interacts with PORCN By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix.
Tissue specificity	Expression is increased in differentiated thyroid carcinomas compared to normal thyroid tissue and anaplastic thyroid tumors where expression is low or undetectable. Expression is found in thyrocytes but not in stromal cells (at protein level). Ref.5
Post-translational modification	Palmitoylation is necessary for stimulation of cell migration, inhibition of the beta-catenin pathway and receptor binding By similarity. Glycosylation is necessary for secretion but not for activity By similarity.
Sequence similarities	Belongs to the Wnt family.

Ontologies

Keywords
Biological process	Chondrogenesis Differentiation Wnt signaling pathway
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Developmental protein
PTM	Glycoprotein Lipoprotein Palmitate
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway, calcium modulating pathway Inferred from electronic annotation. Source: InterPro cartilage development Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Traceable author statement. Source: ProtInc proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell soluble fraction Traceable author statement. Source: ProtInc
Molecular function	receptor binding Ref.1 Traceable author statement. Source: ProtInc signal transducer activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P41221-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P41221-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 35	35	Potential
	Propeptide	36 – 61	26	By similarity		PRO_0000352796
	Chain	62 – 380	319	Protein Wnt-5a		PRO_0000041427
Amino acid modifications
	Lipidation	104	1	S-palmitoyl cysteine By similarity
	Glycosylation	114	1	N-linked (GlcNAc...) Potential
	Glycosylation	120	1	N-linked (GlcNAc...) Potential
	Glycosylation	312	1	N-linked (GlcNAc...) Potential
	Glycosylation	326	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 15	15	Missing in isoform 2.		VSP_035594

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 4, 2008. Version 2. Checksum: 50E73AC7FE96C7B5	FASTA	380	42,339
	10 20 30 40 50 60 MKKSIGILSP GVALGMAGSA MSSKFFLVAL AIFFSFAQVV IEANSWWSLG MNNPVQMSEV 70 80 90 100 110 120 YIIGAQPLCS QLAGLSQGQK KLCHLYQDHM QYIGEGAKTG IKECQYQFRH RRWNCSTVDN 130 140 150 160 170 180 TSVFGRVMQI GSRETAFTYA VSAAGVVNAM SRACREGELS TCGCSRAARP KDLPRDWLWG 190 200 210 220 230 240 GCGDNIDYGY RFAKEFVDAR ERERIHAKGS YESARILMNL HNNEAGRRTV YNLADVACKC 250 260 270 280 290 300 HGVSGSCSLK TCWLQLADFR KVGDALKEKY DSAAAMRLNS RGKLVQVNSR FNSPTTQDLV 310 320 330 340 350 360 YIDPSPDYCV RNESTGSLGT QGRLCNKTSE GMDGCELMCC GRGYDQFKTV QTERCHCKFH 370 380 WCCYVKCKKC TEIVDQFVCK
	Isoform 2. Checksum: 1B869E60D53D583B	FASTA	365	40,887
	10 20 30 40 50 60 MAGSAMSSKF FLVALAIFFS FAQVVIEANS WWSLGMNNPV QMSEVYIIGA QPLCSQLAGL 70 80 90 100 110 120 SQGQKKLCHL YQDHMQYIGE GAKTGIKECQ YQFRHRRWNC STVDNTSVFG RVMQIGSRET 130 140 150 160 170 180 AFTYAVSAAG VVNAMSRACR EGELSTCGCS RAARPKDLPR DWLWGGCGDN IDYGYRFAKE 190 200 210 220 230 240 FVDARERERI HAKGSYESAR ILMNLHNNEA GRRTVYNLAD VACKCHGVSG SCSLKTCWLQ 250 260 270 280 290 300 LADFRKVGDA LKEKYDSAAA MRLNSRGKLV QVNSRFNSPT TQDLVYIDPS PDYCVRNEST 310 320 330 340 350 360 GSLGTQGRLC NKTSEGMDGC ELMCCGRGYD QFKTVQTERC HCKFHWCCYV KCKKCTEIVD QFVCK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21." Clark C.C., Cohen I.R., Eichstetter I., Cannizarro L.A., McPherson J.D., Wasmuth J.J., Iozzo R.V. Genomics 18:249-260(1993) [PubMed: 8288227] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Mesangial cell and Tongue.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[5]	"Wnt-5a has tumor suppressor activity in thyroid carcinoma." Kremenevskaja N., von Wasielewski R., Rao A.S., Schoefl C., Andersson T., Brabant G. Oncogene 24:2144-2154(2005) [PubMed: 15735754] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[6]	"The Wnt5A/protein kinase C pathway mediates motility in melanoma cells via the inhibition of metastasis suppressors and initiation of an epithelial to mesenchymal transition." Dissanayake S.K., Wade M., Johnson C.E., O'Connell M.P., Leotlela P.D., French A.D., Shah K.V., Hewitt K.J., Rosenthal D.T., Indig F.E., Jiang Y., Nickoloff B.J., Taub D.D., Trent J.M., Moon R.T., Bittner M., Weeraratna A.T. J. Biol. Chem. 282:17259-17271(2007) [PubMed: 17426020] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	L20861 mRNA. Translation: AAA16842.1. AK290375 mRNA. Translation: BAF83064.1. AK290869 mRNA. Translation: BAF83558.1. CH471055 Genomic DNA. Translation: EAW65310.1. BC064694 mRNA. Translation: AAH64694.1.
IPI	IPI00013178. IPI00795811.
PIR	A48914.
RefSeq	NP_003383.2.
UniGene	Hs.696364
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	P41221.
Proteomic databases
PRIDE	P41221.
Genome annotation databases
Ensembl	ENSG00000114251. Homo sapiens. [Contig view]
GeneID	7474.
KEGG	hsa:7474.
NMPDR	fig|9606.3.peg.22704.
Organism-specific databases
GeneCards	GC03M055474.
H-InvDB	HIX0003384.
HGNC	HGNC:12784. WNT5A.
MIM	164975. gene.
PharmGKB	PA37385.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P41221.
Enzyme and pathway databases
Pathway_Interaction_DB	wnt_calcium_pathway. Noncanonical Wnt signaling pathway. wnt_signaling_pathway. Wnt signaling.
Gene expression databases
ArrayExpress	P41221.
Bgee	P41221.
CleanEx	HS_WNT5A.
Family and domain databases
InterPro	IPR005816. Wnt_grthfactor. IPR018161. Wnt_grthfactor_CS. IPR005817. Wnt_SF. [Graphical view]
PANTHER	PTHR12027. Wnt. 1 hit.
Pfam	PF00110. wnt. 1 hit. [Graphical view]
PRINTS	PR01349. WNTPROTEIN.
SMART	SM00097. WNT1. 1 hit. [Graphical view]
PROSITE	PS00246. WNT1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

WNT5A_HUMAN

Accession

Primary (citable) accession number: P41221
Secondary accession number(s): A8K4A4, Q6P278

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	November 4, 2008
Last modified:	June 16, 2009
This is version 69 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)