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Protein

Protein Wnt-5a

Gene

Wnt5a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Ligand for members of the frizzled family of seven transmembrane receptors (PubMed:17117926). Can activate or inhibit canonical Wnt signaling, depending on receptor context (PubMed:16602827). 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 (PubMed:16602827). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration (PubMed:17117926). Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor. Mediates motility of melanoma cells (By similarity). Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle (PubMed:10021340). Inhibits type II collagen expression in chondrocytes (By similarity).By similarity4 Publications

Caution

A palmitoylation site was proposed at Cys-104, but it was later shown that this cysteine is engaged in a disulfide bond.Curated

GO - Molecular functioni

  • chemoattractant activity involved in axon guidance Source: ParkinsonsUK-UCL
  • cytokine activity Source: BHF-UCL
  • DNA binding transcription factor activity Source: UniProtKB
  • frizzled binding Source: MGI
  • protein domain specific binding Source: UniProtKB
  • receptor tyrosine kinase-like orphan receptor binding Source: MGI
  • signaling receptor binding Source: ParkinsonsUK-UCL
  • transcription regulatory region DNA binding Source: MGI

GO - Biological processi

  • activation of GTPase activity Source: ParkinsonsUK-UCL
  • activation of JUN kinase activity Source: MGI
  • activation of MAPK activity Source: MGI
  • activation of protein kinase B activity Source: MGI
  • ameboidal-type cell migration Source: MGI
  • animal organ morphogenesis Source: MGI
  • anterior/posterior axis specification, embryo Source: BHF-UCL
  • anterior/posterior pattern specification Source: MGI
  • axis elongation Source: MGI
  • axonal fasciculation Source: ParkinsonsUK-UCL
  • axon guidance Source: UniProtKB
  • axonogenesis Source: ParkinsonsUK-UCL
  • canonical Wnt signaling pathway Source: BHF-UCL
  • cartilage development Source: UniProtKB-KW
  • cell-cell signaling Source: MGI
  • cell fate commitment Source: GO_Central
  • cell migration Source: MGI
  • cellular protein localization Source: MGI
  • cellular response to calcium ion Source: Ensembl
  • cellular response to interferon-gamma Source: Ensembl
  • cellular response to lipopolysaccharide Source: Ensembl
  • cellular response to molecule of bacterial origin Source: BHF-UCL
  • cellular response to transforming growth factor beta stimulus Source: Ensembl
  • cervix development Source: MGI
  • chemoattraction of serotonergic neuron axon Source: ParkinsonsUK-UCL
  • chemorepulsion of dopaminergic neuron axon Source: ParkinsonsUK-UCL
  • cochlea morphogenesis Source: MGI
  • convergent extension Source: MGI
  • convergent extension involved in axis elongation Source: MGI
  • convergent extension involved in organogenesis Source: MGI
  • determination of left/right symmetry Source: MGI
  • development of primary male sexual characteristics Source: MGI
  • digestive tract morphogenesis Source: MGI
  • dopaminergic neuron differentiation Source: CACAO
  • embryonic digit morphogenesis Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • embryonic skeletal system development Source: MGI
  • epithelial cell proliferation involved in mammary gland duct elongation Source: MGI
  • establishment of epithelial cell apical/basal polarity Source: MGI
  • establishment of planar polarity Source: MGI
  • face development Source: MGI
  • genitalia development Source: MGI
  • heart looping Source: MGI
  • hematopoietic stem cell proliferation Source: MGI
  • hindgut morphogenesis Source: MGI
  • hypophysis morphogenesis Source: MGI
  • inner ear morphogenesis Source: MGI
  • JNK cascade Source: MGI
  • keratinocyte differentiation Source: Ensembl
  • lateral sprouting involved in mammary gland duct morphogenesis Source: MGI
  • limb morphogenesis Source: MGI
  • lung development Source: MGI
  • male gonad development Source: MGI
  • mammary gland branching involved in thelarche Source: MGI
  • melanocyte proliferation Source: CACAO
  • mesenchymal-epithelial cell signaling Source: MGI
  • mesodermal to mesenchymal transition involved in gastrulation Source: MGI
  • midbrain development Source: ParkinsonsUK-UCL
  • midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • midgut development Source: MGI
  • morphogenesis of an epithelium Source: MGI
  • negative chemotaxis Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of axon extension involved in axon guidance Source: MGI
  • negative regulation of BMP signaling pathway Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • negative regulation of cell proliferation in midbrain Source: ParkinsonsUK-UCL
  • negative regulation of epithelial cell proliferation Source: MGI
  • negative regulation of fat cell differentiation Source: MGI
  • negative regulation of fibroblast growth factor receptor signaling pathway Source: MGI
  • negative regulation of melanin biosynthetic process Source: CACAO
  • negative regulation of mesenchymal cell proliferation Source: MGI
  • negative regulation of prostatic bud formation Source: MGI
  • negative regulation of synapse assembly Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: MGI
  • neural tube closure Source: MGI
  • neural tube development Source: MGI
  • neurogenesis Source: ParkinsonsUK-UCL
  • neuron projection morphogenesis Source: UniProtKB
  • non-canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • non-canonical Wnt signaling pathway via JNK cascade Source: BHF-UCL
  • notochord morphogenesis Source: MGI
  • olfactory bulb interneuron development Source: UniProtKB
  • paraxial mesoderm formation Source: MGI
  • pericardium morphogenesis Source: MGI
  • planar cell polarity pathway involved in axis elongation Source: MGI
  • planar cell polarity pathway involved in axon guidance Source: ParkinsonsUK-UCL
  • planar cell polarity pathway involved in cardiac muscle tissue morphogenesis Source: MGI
  • planar cell polarity pathway involved in cardiac right atrium morphogenesis Source: MGI
  • planar cell polarity pathway involved in gastrula mediolateral intercalation Source: MGI
  • planar cell polarity pathway involved in neural tube closure Source: MGI
  • planar cell polarity pathway involved in outflow tract morphogenesis Source: MGI
  • planar cell polarity pathway involved in pericardium morphogenesis Source: MGI
  • planar cell polarity pathway involved in ventricular septum morphogenesis Source: MGI
  • positive regulation of angiogenesis Source: MGI
  • positive regulation of canonical Wnt signaling pathway Source: CAFA
  • positive regulation of cartilage development Source: MGI
  • positive regulation of cell-cell adhesion Source: MGI
  • positive regulation of cell-cell adhesion mediated by cadherin Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of cGMP metabolic process Source: MGI
  • positive regulation of chemokine biosynthetic process Source: MGI
  • positive regulation of cytokine production Source: MGI
  • positive regulation of cytokine secretion involved in immune response Source: MGI
  • positive regulation of endocytosis Source: MGI
  • positive regulation of endothelial cell migration Source: MGI
  • positive regulation of endothelial cell proliferation Source: MGI
  • positive regulation of epithelial cell proliferation Source: MGI
  • positive regulation of fibroblast proliferation Source: MGI
  • positive regulation of gene expression Source: ARUK-UCL
  • positive regulation of G-protein coupled receptor protein signaling pathway Source: Ensembl
  • positive regulation of GTPase activity Source: ParkinsonsUK-UCL
  • positive regulation of inflammatory response Source: MGI
  • positive regulation of interferon-gamma production Source: BHF-UCL
  • positive regulation of interleukin-1 beta secretion Source: BHF-UCL
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of interleukin-8 secretion Source: BHF-UCL
  • positive regulation of JNK cascade Source: BHF-UCL
  • positive regulation of JUN kinase activity Source: MGI
  • positive regulation of macrophage activation Source: MGI
  • positive regulation of macrophage cytokine production Source: MGI
  • positive regulation of meiotic nuclear division Source: MGI
  • positive regulation of mesenchymal cell proliferation Source: MGI
  • positive regulation of neuron death Source: ARUK-UCL
  • positive regulation of neuron projection arborization Source: ARUK-UCL
  • positive regulation of neuron projection development Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: MGI
  • positive regulation of non-canonical Wnt signaling pathway Source: CACAO
  • positive regulation of ossification Source: MGI
  • positive regulation of peptidyl-serine phosphorylation Source: MGI
  • positive regulation of peptidyl-threonine phosphorylation Source: MGI
  • positive regulation of protein binding Source: ParkinsonsUK-UCL
  • positive regulation of protein catabolic process Source: MGI
  • positive regulation of protein kinase activity Source: ParkinsonsUK-UCL
  • positive regulation of protein kinase C activity Source: MGI
  • positive regulation of protein kinase C signaling Source: MGI
  • positive regulation of protein phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of response to cytokine stimulus Source: MGI
  • positive regulation of T cell chemotaxis Source: MGI
  • positive regulation of thymocyte apoptotic process Source: MGI
  • positive regulation of timing of anagen Source: CAFA
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • positive regulation of tumor necrosis factor secretion Source: ARUK-UCL
  • positive regulation of type I interferon-mediated signaling pathway Source: MGI
  • post-anal tail morphogenesis Source: MGI
  • primitive streak formation Source: MGI
  • protein phosphorylation Source: MGI
  • regulation of branching involved in mammary gland duct morphogenesis Source: MGI
  • regulation of cellular protein localization Source: ParkinsonsUK-UCL
  • regulation of I-kappaB kinase/NF-kappaB signaling Source: ARUK-UCL
  • regulation of protein localization Source: MGI
  • secondary palate development Source: MGI
  • signal transduction Source: MGI
  • somite development Source: MGI
  • somitogenesis Source: MGI
  • tube closure Source: MGI
  • type B pancreatic cell development Source: MGI
  • urinary bladder development Source: MGI
  • uterus development Source: MGI
  • vagina development Source: MGI
  • Wnt signaling pathway Source: MGI
  • Wnt signaling pathway, calcium modulating pathway Source: BHF-UCL
  • Wnt signaling pathway, planar cell polarity pathway Source: MGI
  • Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • wound healing Source: MGI

Keywordsi

Molecular functionDevelopmental protein
Biological processChondrogenesis, Differentiation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-3238698 WNT ligand biogenesis and trafficking
R-MMU-4086398 Ca2+ pathway
R-MMU-4086400 PCP/CE pathway
R-MMU-4608870 Asymmetric localization of PCP proteins
R-MMU-5099900 WNT5A-dependent internalization of FZD4
R-MMU-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-MMU-8856825 Cargo recognition for clathrin-mediated endocytosis
R-MMU-8856828 Clathrin-mediated endocytosis

Names & Taxonomyi

Protein namesi
Recommended name:
Protein Wnt-5a
Gene namesi
Name:Wnt5a
Synonyms:Wnt-5a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:98958 Wnt5a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Disruption phenotypei

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.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi104C → A: No effect on secretion. 1 Publication1
Mutagenesisi114N → Q: Abolishes glycosylation; when associated with Q-120, Q-312 and Q-326. 1 Publication1
Mutagenesisi120N → Q: Abolishes glycosylation; when associated with Q-114, Q-312 and Q-326. 1 Publication1
Mutagenesisi312N → Q: Abolishes glycosylation; when associated with Q-114, Q-120 and Q-326. 1 Publication1
Mutagenesisi326N → Q: Abolishes glycosylation; when associated with Q-114, Q-120 and Q-312. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 37Sequence analysisAdd BLAST37
PropeptideiPRO_000035279738 – 611 PublicationAdd BLAST24
ChainiPRO_000004142862 – 380Protein Wnt-5aAdd BLAST319

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi104 ↔ 115By similarity
Glycosylationi114N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi120N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi154 ↔ 162By similarity
Disulfide bondi164 ↔ 182By similarity
Disulfide bondi238 ↔ 252By similarity
Disulfide bondi240 ↔ 247By similarity
Lipidationi244O-palmitoleoyl serine; by PORCNBy similarity1
Glycosylationi312N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi325 ↔ 340By similarity
Glycosylationi326N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi355 ↔ 370By similarity
Disulfide bondi357 ↔ 367By similarity
Disulfide bondi362 ↔ 363By similarity

Post-translational modificationi

Glycosylation is necessary for secretion but not for activity.1 Publication
Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.By similarity
Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT5A.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein

Proteomic databases

MaxQBiP22725
PaxDbiP22725
PeptideAtlasiP22725
PRIDEiP22725

PTM databases

iPTMnetiP22725
PhosphoSitePlusiP22725
SwissPalmiP22725

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiENSMUSG00000021994
CleanExiMM_WNT5A
GenevisibleiP22725 MM

Interactioni

Subunit structurei

Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids (By similarity). Homooligomer; disulfide-linked, leading to inactivation (PubMed:22726442). Interacts with PORCN (PubMed:10866835). Interacts with WLS (PubMed:19841259).By similarity3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • chemoattractant activity involved in axon guidance Source: ParkinsonsUK-UCL
  • cytokine activity Source: BHF-UCL
  • frizzled binding Source: MGI
  • protein domain specific binding Source: UniProtKB
  • receptor tyrosine kinase-like orphan receptor binding Source: MGI
  • signaling receptor binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi204577, 7 interactors
DIPiDIP-39893N
IntActiP22725, 6 interactors
MINTiP22725
STRINGi10090.ENSMUSP00000064878

Structurei

3D structure databases

ProteinModelPortaliP22725
SMRiP22725
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Wnt family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3913 Eukaryota
ENOG410XQZ1 LUCA
GeneTreeiENSGT00760000118943
HOGENOMiHOG000039529
HOVERGENiHBG001595
InParanoidiP22725
KOiK00444
OMAiHDLVYID
OrthoDBiEOG091G0OFF
PhylomeDBiP22725
TreeFamiTF105310

Family and domain databases

InterProiView protein in InterPro
IPR005817 Wnt
IPR026538 Wnt5a
IPR018161 Wnt_CS
PANTHERiPTHR12027 PTHR12027, 1 hit
PTHR12027:SF33 PTHR12027:SF33, 1 hit
PfamiView protein in Pfam
PF00110 wnt, 1 hit
PRINTSiPR01349 WNTPROTEIN
SMARTiView protein in SMART
SM00097 WNT1, 1 hit
PROSITEiView protein in PROSITE
PS00246 WNT1, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P22725-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKKPIGILSP GVALGTAGGA MSSKFFLMAL ATFFSFAQVV IEANSWWSLG
60 70 80 90 100
MNNPVQMSEV YIIGAQPLCS QLAGLSQGQK KLCHLYQDHM QYIGEGAKTG
110 120 130 140 150
IKECQYQFRH RRWNCSTVDN TSVFGRVMQI GSRETAFTYA VSAAGVVNAM
160 170 180 190 200
SRACREGELS TCGCSRAARP KDLPRDWLWG GCGDNIDYGY RFAKEFVDAR
210 220 230 240 250
ERERIHAKGS YESARILMNL HNNEAGRRTV YNLADVACKC HGVSGSCSLK
260 270 280 290 300
TCWLQLADFR KVGDALKEKY DSAAAMRLNS RGKLVQVNSR FNSPTTQDLV
310 320 330 340 350
YIDPSPDYCV RNESTGSLGT QGRLCNKTSE GMDGCELMCC GRGYDQFKTV
360 370 380
QTERCHCKFH WCCYVKCKKC TEIVDQFVCK
Length:380
Mass (Da):42,309
Last modified:November 4, 2008 - v2
Checksum:i64CA36C516D22D8A
GO
Isoform 2 (identifier: P22725-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:360
Mass (Da):40,489
Checksum:i626372A278164C18
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti168Missing in AAA40567 (PubMed:2279700).Curated1
Sequence conflicti190 – 191YR → HP in AAA40567 (PubMed:2279700).Curated2
Sequence conflicti377F → L in BAC27430 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0355951 – 20Missing in isoform 2. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M89798 mRNA Translation: AAA40567.1
AK031512 mRNA Translation: BAC27430.1
AK031597 mRNA Translation: BAC27468.1
AK036824 mRNA Translation: BAC29593.1
CT025649 Genomic DNA No translation available.
BC018425 mRNA Translation: AAH18425.1
CCDSiCCDS26888.1 [P22725-1]
CCDS56946.1 [P22725-2]
PIRiD36470
RefSeqiNP_001243153.1, NM_001256224.1 [P22725-2]
NP_033550.2, NM_009524.3 [P22725-1]
XP_006518987.1, XM_006518924.2 [P22725-2]
XP_006518988.1, XM_006518925.3 [P22725-2]
UniGeneiMm.287544

Genome annotation databases

EnsembliENSMUST00000063465; ENSMUSP00000064878; ENSMUSG00000021994 [P22725-1]
ENSMUST00000112272; ENSMUSP00000107891; ENSMUSG00000021994 [P22725-2]
GeneIDi22418
KEGGimmu:22418
UCSCiuc007sug.2 mouse [P22725-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiWNT5A_MOUSE
AccessioniPrimary (citable) accession number: P22725
Secondary accession number(s): Q8BM17, Q8BMF9, Q8VCV6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: November 4, 2008
Last modified: July 18, 2018
This is version 170 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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