Reviewed, UniProtKB/Swiss-Prot P22725 (WNT5A_MOUSE)

Names and origin

Protein names

Recommended name:
    Protein Wnt-5a

Gene names

Name:	Wnt5a
Synonyms:	Wnt-5a

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

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 Ref.8 Ref.9
Subunit structure	Interacts with PORCN. Ref.7
Subcellular location	Secreted › extracellular space › extracellular matrix.
Tissue specificity	Expressed in a gradient at the caudal end of the embryo during gastrulation and later in the distal-most aspect of several structures that extend from the body such as the limbs and genital tubercle. Ref.6
Post-translational modification	Palmitoylation is necessary for stimulation of cell migration, inhibition of the beta-catenin pathway and receptor binding. Glycosylation is necessary for secretion but not for activity.
Disruption phenotype	Mice display perinatal lethality and display gross morphological defects in outgrowing tissues. They are truncated caudally, displaying loss of the tail and a significant shortening of the anterior-posterior axis. The shape of the head is abnormal with truncated snout, mandible and tongue and reduced outgrowth of the external ear. Fore- and hindlimbs lack digits, the genital tubercle is missing and chondrocyte differentiation is inhibited. Ref.6 Ref.8
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
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	JNK cascade Inferred from direct assay. Source: MGI 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 Traceable author statement. Source: MGI embryonic limb morphogenesis Ref.6 Inferred from mutant phenotype. Source: MGI epithelial cell proliferation involved in mammary gland duct elongation Inferred from direct assay. Source: MGI hindgut morphogenesis Inferred from mutant phenotype. Source: MGI hypophysis morphogenesis Inferred from mutant phenotype. Source: MGI lateral sprouting involved in mammary gland duct morphogenesis Inferred from direct assay. Source: MGI lung development Inferred from mutant phenotype. Source: MGI male gonad development Inferred from mutant phenotype. Source: MGI mammary gland branching involved in thelarche Inferred from direct assay. Source: MGI negative regulation of epithelial cell proliferation Inferred from direct assay. Source: MGI negative regulation of prostatic bud formation Inferred from mutant phenotype. Source: MGI protein amino acid phosphorylation Inferred from genetic interaction. Source: MGI regulation of branching involved in mammary gland duct morphogenesis Inferred from direct assay. Source: MGI urinary bladder development Inferred from mutant phenotype. Source: MGI
Cellular component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	receptor binding Traceable author statement. Source: MGI signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Kl	O35082	1	EBI-1570983,EBI-1570828

Alternative products

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

Isoform 1 (identifier: P22725-1)

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: P22725-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-20: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 37	37	Potential
	Propeptide	38 – 61	24			PRO_0000352797
	Chain	62 – 380	319	Protein Wnt-5a		PRO_0000041428
Amino acid modifications
	Lipidation	104	1	S-palmitoyl cysteine Ref.9
	Glycosylation	114	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	120	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	312	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	326	1	N-linked (GlcNAc...) Ref.9
Natural variations
	Alternative sequence	1 – 20	20	Missing in isoform 2.		VSP_035595
Experimental info
	Mutagenesis	104	1	C → A: Abolishes palmitoylation. No effect on secretion. Ref.9
	Mutagenesis	114	1	N → Q: Abolishes glycosylation; when associated with Q-120, Q-312 and Q-326. Ref.9
	Mutagenesis	120	1	N → Q: Abolishes glycosylation; when associated with Q-114, Q-312 and Q-326. Ref.9
	Mutagenesis	312	1	N → Q: Abolishes glycosylation; when associated with Q-114, Q-120 and Q-326. Ref.9
	Mutagenesis	326	1	N → Q: Abolishes glycosylation; when associated with Q-114, Q-120 and Q-312. Ref.9
	Sequence conflict	168	1	Missing in AAA40567. Ref.1
	Sequence conflict	190 – 191	2	YR → HP in AAA40567. Ref.1
	Sequence conflict	377	1	F → L in BAC27430. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 4, 2008. Version 2. Checksum: 64CA36C516D22D8A	FASTA	380	42,309
	10 20 30 40 50 60 MKKPIGILSP GVALGTAGGA MSSKFFLMAL ATFFSFAQVV 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: 626372A278164C18	FASTA	360	40,489
	10 20 30 40 50 60 MSSKFFLMAL ATFFSFAQVV IEANSWWSLG MNNPVQMSEV YIIGAQPLCS QLAGLSQGQK 70 80 90 100 110 120 KLCHLYQDHM QYIGEGAKTG IKECQYQFRH RRWNCSTVDN TSVFGRVMQI GSRETAFTYA 130 140 150 160 170 180 VSAAGVVNAM SRACREGELS TCGCSRAARP KDLPRDWLWG GCGDNIDYGY RFAKEFVDAR 190 200 210 220 230 240 ERERIHAKGS YESARILMNL HNNEAGRRTV YNLADVACKC HGVSGSCSLK TCWLQLADFR 250 260 270 280 290 300 KVGDALKEKY DSAAAMRLNS RGKLVQVNSR FNSPTTQDLV YIDPSPDYCV RNESTGSLGT 310 320 330 340 350 360 QGRLCNKTSE GMDGCELMCC GRGYDQFKTV QTERCHCKFH WCCYVKCKKC TEIVDQFVCK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development." Gavin B.J., McMahon J.A., McMahon A.P. Genes Dev. 4:2319-2332(1990) [PubMed: 2279700] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Embryo.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Testis and Vagina.
[3]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[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: Mammary tumor.
[5]	"Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context." Mikels A.J., Nusse R. PLoS Biol. 4:E115-E115(2006) [PubMed: 16602827] [Abstract] Cited for: PROTEIN SEQUENCE OF 62-82, FUNCTION.
[6]	"A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo." Yamaguchi T.P., Bradley A., McMahon A.P., Jones S. Development 126:1211-1223(1999) [PubMed: 10021340] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[7]	"The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family." Tanaka K., Okabayashi H., Asashima M., Perrimon N., Kadowaki T. Eur. J. Biochem. 267:4300-4311(2000) [PubMed: 10866835] [Abstract] Cited for: INTERACTION WITH PORCN.
[8]	"Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation." Topol L., Jiang X., Choi H., Garrett-Beal L., Carolan P.J., Yang Y. J. Cell Biol. 162:899-908(2003) [PubMed: 12952940] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[9]	"Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling." Kurayoshi M., Yamamoto H., Izumi S., Kikuchi A. Biochem. J. 402:515-523(2007) [PubMed: 17117926] [Abstract] Cited for: FUNCTION, PALMITOYLATION AT CYS-104, GLYCOSYLATION AT ASN-114; ASN-120; ASN-312 AND ASN-326, MUTAGENESIS OF CYS-104; ASN-114; ASN-120; ASN-312 AND ASN-326.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M89798 mRNA. Translation: AAA40567.1. AK031512 mRNA. Translation: BAC27430.1. AK031597 mRNA. Translation: BAC27468.1. AK036824 mRNA. Translation: BAC29593.1. CT025649 Genomic DNA. Translation: CAM27826.1. CT025649 Genomic DNA. Translation: CAM27827.1. BC018425 mRNA. Translation: AAH18425.1.
IPI	IPI00410980. IPI00831451.
PIR	D36470.
RefSeq	NP_033550.2.
UniGene	Mm.287544
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P22725. 1 interaction.
STRING	P22725.
Proteomic databases
PRIDE	P22725.
Genome annotation databases
Ensembl	ENSMUST00000063465; ENSMUSP00000064878; ENSMUSG00000021994; Mus musculus. [Genome view] ENSMUST00000112274; ENSMUSP00000107893; ENSMUSG00000021994; Mus musculus. [Genome view]
GeneID	22418.
KEGG	mmu:22418.
UCSC	uc007sug.1. mouse.
Organism-specific databases
CTD	22418.
MGI	MGI:98958. Wnt5a.
Phylogenomic databases
HOVERGEN	P22725.
Gene expression databases
ArrayExpress	P22725.
Bgee	P22725.
CleanEx	MM_WNT5A.
Genevestigator	P22725.
GermOnline	ENSMUSG00000021994. Mus musculus.
Family and domain databases
InterPro	IPR005816. Wnt_grthfactor. IPR018161. Wnt_grthfactor_CS. [Graphical view]
PRINTS	PR01349. WNTPROTEIN.
PROSITE	PS00246. WNT1. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

WNT5A_MOUSE

Accession

Primary (citable) accession number: P22725
Secondary accession number(s): Q8BM17, Q8BMF9, Q8VCV6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	November 4, 2008
Last modified:	October 13, 2009
This is version 81 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)