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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

GO - Biological processi

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 Expressed in 409 organ(s), highest expression level in epididymis
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). Interacts with glypican GCP3 (By similarity).By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

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

Cross-referencesi

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

3D structure databases

ProteinModelPortaliP22725
SMRiP22725
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

PTM databases

iPTMnetiP22725
PhosphoSitePlusiP22725
SwissPalmiP22725

Proteomic databases

MaxQBiP22725
PaxDbiP22725
PeptideAtlasiP22725
PRIDEiP22725

Protocols and materials databases

DNASUi22418
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7474
MGIiMGI:98958 Wnt5a

Phylogenomic databases

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

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

Miscellaneous databases

ChiTaRSiWnt5a mouse
PROiPR:P22725
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021994 Expressed in 409 organ(s), highest expression level in epididymis
CleanExiMM_WNT5A
GenevisibleiP22725 MM

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
ProtoNetiSearch...

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: October 10, 2018
This is version 172 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. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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