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Protein

Protein Wnt-5a

Gene

WNT5A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (By similarity). 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 (PubMed:15735754). Mediates motility of melanoma cells (PubMed:17426020). 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 (By similarity).By similarity2 Publications

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processChondrogenesis, Differentiation, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-3238698 WNT ligand biogenesis and trafficking
R-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-3772470 Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-4086398 Ca2+ pathway
R-HSA-4086400 PCP/CE pathway
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiP41221
SIGNORiP41221

Names & Taxonomyi

Protein namesi
Recommended name:
Protein Wnt-5a
Gene namesi
Name:WNT5A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000114251.13
HGNCiHGNC:12784 WNT5A
MIMi164975 gene
neXtProtiNX_P41221

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

Involvement in diseasei

Robinow syndrome, autosomal dominant 1 (DRS1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia. The clinical signs are generally milder in dominant cases.
See also OMIM:180700
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06662383C → S in DRS1; hypomorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs786200925EnsemblClinVar.1
Natural variantiVAR_066629182C → R in DRS1; hypomorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs387906663EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi7474
MalaCardsiWNT5A
MIMi180700 phenotype
OpenTargetsiENSG00000114251
Orphaneti3107 Autosomal dominant Robinow syndrome
PharmGKBiPA37385

Polymorphism and mutation databases

BioMutaiWNT5A
DMDMi212276478

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 35Sequence analysisAdd BLAST35
PropeptideiPRO_000035279636 – 61By similarityAdd BLAST26
ChainiPRO_000004142762 – 380Protein Wnt-5aAdd BLAST319

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi104 ↔ 115By similarity
Glycosylationi114N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi120N-linked (GlcNAc...) asparagineSequence analysis1
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...) asparagineSequence analysis1
Disulfide bondi325 ↔ 340By similarity
Glycosylationi326N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi355 ↔ 370By similarity
Disulfide bondi357 ↔ 367By similarity
Disulfide bondi362 ↔ 363By similarity

Post-translational modificationi

Glycosylation is necessary for secretion but not for activity.By similarity
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.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein

Proteomic databases

MaxQBiP41221
PaxDbiP41221
PeptideAtlasiP41221
PRIDEiP41221
ProteomicsDBi55429
55430 [P41221-2]

PTM databases

GlyConnecti1672
iPTMnetiP41221
PhosphoSitePlusiP41221

Expressioni

Tissue specificityi

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) (PubMed:15735754). Detected in neonate heart and lung (PubMed:8288227).2 Publications

Gene expression databases

BgeeiENSG00000114251 Expressed in 199 organ(s), highest expression level in endometrium
CleanExiHS_WNT5A
ExpressionAtlasiP41221 baseline and differential
GenevisibleiP41221 HS

Interactioni

Subunit structurei

Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (PubMed:26902720). The complex with AFM may represent the physiological form in body fluids (PubMed:26902720). Homooligomer; disulfide-linked, leading to inactivation (in vitro). Interacts with PORCN. Interacts with WLS (By similarity). Interacts with glypican GCP3 (PubMed:14610063).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
WIF1Q9Y5W52EBI-6594545,EBI-3922719

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113311, 28 interactors
DIPiDIP-29735N
IntActiP41221, 5 interactors
MINTiP41221
STRINGi9606.ENSP00000264634

Structurei

3D structure databases

ProteinModelPortaliP41221
SMRiP41221
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the Wnt family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3913 Eukaryota
ENOG410XQZ1 LUCA
GeneTreeiENSGT00760000118943
HOVERGENiHBG001595
InParanoidiP41221
KOiK00444
OMAiIVERCHC
OrthoDBiEOG091G0OFF
PhylomeDBiP41221
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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P41221-1) [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
MKKSIGILSP GVALGMAGSA MSSKFFLVAL AIFFSFAQVV 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):42,339
Last modified:November 4, 2008 - v2
Checksum:i50E73AC7FE96C7B5
GO
Isoform 2 (identifier: P41221-2) [UniParc]FASTAAdd to basket

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

Show »
Length:365
Mass (Da):40,887
Checksum:i1B869E60D53D583B
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J8I8C9J8I8_HUMAN
Protein Wnt
WNT5A
214Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06662383C → S in DRS1; hypomorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs786200925EnsemblClinVar.1
Natural variantiVAR_066629182C → R in DRS1; hypomorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs387906663EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0355941 – 15Missing in isoform 2. 2 PublicationsAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS46850.1 [P41221-1]
CCDS58835.1 [P41221-2]
PIRiA48914
RefSeqiNP_001243034.1, NM_001256105.1 [P41221-2]
NP_003383.2, NM_003392.4 [P41221-1]
XP_006713387.1, XM_006713324.1 [P41221-2]
XP_011532387.1, XM_011534085.2 [P41221-2]
XP_011532388.1, XM_011534086.2 [P41221-2]
XP_011532389.1, XM_011534087.2 [P41221-2]
XP_011532390.1, XM_011534088.2 [P41221-2]
XP_011532391.1, XM_011534089.1 [P41221-2]
XP_016862617.1, XM_017007128.1 [P41221-2]
UniGeneiHs.643085

Genome annotation databases

EnsembliENST00000264634; ENSP00000264634; ENSG00000114251 [P41221-1]
ENST00000474267; ENSP00000417310; ENSG00000114251 [P41221-1]
ENST00000497027; ENSP00000420104; ENSG00000114251 [P41221-2]
GeneIDi7474
KEGGihsa:7474
UCSCiuc003dhn.5 human [P41221-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS46850.1 [P41221-1]
CCDS58835.1 [P41221-2]
PIRiA48914
RefSeqiNP_001243034.1, NM_001256105.1 [P41221-2]
NP_003383.2, NM_003392.4 [P41221-1]
XP_006713387.1, XM_006713324.1 [P41221-2]
XP_011532387.1, XM_011534085.2 [P41221-2]
XP_011532388.1, XM_011534086.2 [P41221-2]
XP_011532389.1, XM_011534087.2 [P41221-2]
XP_011532390.1, XM_011534088.2 [P41221-2]
XP_011532391.1, XM_011534089.1 [P41221-2]
XP_016862617.1, XM_017007128.1 [P41221-2]
UniGeneiHs.643085

3D structure databases

ProteinModelPortaliP41221
SMRiP41221
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113311, 28 interactors
DIPiDIP-29735N
IntActiP41221, 5 interactors
MINTiP41221
STRINGi9606.ENSP00000264634

PTM databases

GlyConnecti1672
iPTMnetiP41221
PhosphoSitePlusiP41221

Polymorphism and mutation databases

BioMutaiWNT5A
DMDMi212276478

Proteomic databases

MaxQBiP41221
PaxDbiP41221
PeptideAtlasiP41221
PRIDEiP41221
ProteomicsDBi55429
55430 [P41221-2]

Protocols and materials databases

DNASUi7474
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264634; ENSP00000264634; ENSG00000114251 [P41221-1]
ENST00000474267; ENSP00000417310; ENSG00000114251 [P41221-1]
ENST00000497027; ENSP00000420104; ENSG00000114251 [P41221-2]
GeneIDi7474
KEGGihsa:7474
UCSCiuc003dhn.5 human [P41221-1]

Organism-specific databases

CTDi7474
DisGeNETi7474
EuPathDBiHostDB:ENSG00000114251.13
GeneCardsiWNT5A
HGNCiHGNC:12784 WNT5A
MalaCardsiWNT5A
MIMi164975 gene
180700 phenotype
neXtProtiNX_P41221
OpenTargetsiENSG00000114251
Orphaneti3107 Autosomal dominant Robinow syndrome
PharmGKBiPA37385
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3913 Eukaryota
ENOG410XQZ1 LUCA
GeneTreeiENSGT00760000118943
HOVERGENiHBG001595
InParanoidiP41221
KOiK00444
OMAiIVERCHC
OrthoDBiEOG091G0OFF
PhylomeDBiP41221
TreeFamiTF105310

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-3238698 WNT ligand biogenesis and trafficking
R-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-3772470 Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-4086398 Ca2+ pathway
R-HSA-4086400 PCP/CE pathway
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-5140745 WNT5A-dependent internalization of FZD2, FZD5 and ROR2
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiP41221
SIGNORiP41221

Miscellaneous databases

ChiTaRSiWNT5A human
GeneWikiiWNT5A
GenomeRNAii7474
PROiPR:P41221
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114251 Expressed in 199 organ(s), highest expression level in endometrium
CleanExiHS_WNT5A
ExpressionAtlasiP41221 baseline and differential
GenevisibleiP41221 HS

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_HUMAN
AccessioniPrimary (citable) accession number: P41221
Secondary accession number(s): A8K4A4, Q6P278
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 4, 2008
Last modified: November 7, 2018
This is version 168 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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