WNT5A Wnt family member 5A [ Homo sapiens (human) ]

Gene ID: 7474, updated on 14-Jun-2020

Summary

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Official Symbol: WNT5Aprovided by HGNC
Official Full Name: Wnt family member 5Aprovided by HGNC
Primary source: HGNC:HGNC:12784
See related: Ensembl:ENSG00000114251 MIM:164975
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: hWNT5A
Summary: The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis. Mutations in this gene are the cause of autosomal dominant Robinow syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
Expression: Broad expression in urinary bladder (RPKM 9.1), endometrium (RPKM 7.3) and 19 other tissues See more
Orthologs: mouse all

Genomic context

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See WNT5A in Genome Data Viewer

Location:: 3p14.3

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	3	NC_000003.12 (55465715..55505261, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (55499743..55521670, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The inhibition of endogenous Wnt5a demonstrated that an autocrine Wnt5a loop is a major regulator of the NF-kappaB pathway in melanoma. Results indicate that Wnt5a activates the NF-kappaB pathway and has an immunomodulatory effect on melanoma through the secretion of cytokines and chemokines.
Title: An Autocrine Wnt5a Loop Promotes NF-κB Pathway Activation and Cytokine/Chemokine Secretion in Melanoma.
The transfection of peripheral blood CLL cells with STAT3 short hairpin RNA downregulated Wnt5a mRNA and protein levels, suggesting that STAT3 binds to the Wnt5a gene promoter and induces the expression of Wnt5a in CLL cells.
Title: STAT3-Induced Wnt5a Provides Chronic Lymphocytic Leukemia Cells with Survival Advantage.
data reveal that the true nature of Wnt5a in inflammatory cells, is to regulate TLR signals, and in myeloid cells it acts as an endogenous, tolerance-associated molecular pattern (TAMP), inducing IL-10 and innate immune tolerance
Title: Wnt5a is a TLR2/4-ligand that induces tolerance in human myeloid cells.
WNT5AC83S consistently caused a delay in ossification and bones were more than 50% shorter and 200% wider than controls. The chicken and human Robinow syndrome phenotypes are produced from the C83S mutation, even though the variant protein is less abundant than wtWNT5A. It is concluded the variant protein has dominant-negative effects on chondrogenesis leading to limb abnormalities.
Title: Robinow syndrome skeletal phenotypes caused by the WNT5AC83S variant are due to dominant interference with chondrogenesis.
Low WNT5A expression is associated with proliferation and migration of hepatocellular carcinoma.
Title: Up-regulation of Wnt5a inhibits proliferation and migration of hepatocellular carcinoma cells.
Fz2 and Wnt5a, might be involved in human Amyotrophic lateral sclerosis pathology.
Title: Wnt Signaling Alterations in the Human Spinal Cord of Amyotrophic Lateral Sclerosis Cases: Spotlight on Fz2 and Wnt5a.
Wnt5a is a key mediator for the establishment of pulmonary endothelium-pericyte interactions, and its loss could contribute to pulmonary artery hypertension by reducing the viability of newly formed vessels.
Title: Loss of Endothelium-Derived Wnt5a Is Associated With Reduced Pericyte Recruitment and Small Vessel Loss in Pulmonary Arterial Hypertension.
Low WNT5A expression is associated with bladder cancer invasion.
Title: SOX4 regulates invasion of bladder cancer cells via repression of WNT5a.
these results demonstrate that Wnt5a/ROR2/SIAH2 signaling axis plays a crucial role in inducing and maintaining prostate cancer cells dormancy in bone.
Title: Wnt5a induces and maintains prostate cancer cells dormancy in bone.
Overexpression of miR-129-5 inhibited the expression of Wnt5a, thus blocking the protein kinase C(PKC)/ERK/NF-kappaB and JNK pathways.
Title: miR-129-5p targets Wnt5a to block PKC/ERK/NF-κB and JNK pathways in glioblastoma.

Submit: New GeneRIF Correction See all GeneRIFs (334)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Robinow syndrome, autosomal dominant 1 MedGen: C4551475 OMIM: 180700 GeneReviews: Autosomal Dominant Robinow Syndrome	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 upregulates the expression of WNT5a in human neural stem cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH78427 (e-PCR)
- UniSTS:51220

SHGC-77018 (e-PCR)
- UniSTS:65072

RH102004 (e-PCR)
- UniSTS:96338

G35315 (e-PCR)
- UniSTS:2149

NoName (e-PCR)
- UniSTS:481910

Wnt5a (e-PCR), detects polymorphism
- UniSTS:277885

RH80790 (e-PCR)
- UniSTS:92060

G15856 (e-PCR)
- UniSTS:3037

NoName (e-PCR)
- UniSTS:480766

Homology

Homologs of the WNT5A gene: The WNT5A gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 287 organisms have orthologs with human gene WNT5A
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
chemoattractant activity involved in axon guidance	IEA Inferred from Electronic Annotation more info
cytokine activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
frizzled binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
frizzled binding	IPI Inferred from Physical Interaction more info	PubMed
frizzled binding	TAS Traceable Author Statement more info	PubMed
phospholipid binding	TAS Traceable Author Statement more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein domain specific binding	IEA Inferred from Electronic Annotation more info
receptor ligand activity	IC Inferred by Curator more info	PubMed
receptor tyrosine kinase-like orphan receptor binding	IPI Inferred from Physical Interaction more info	PubMed
transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
Wnt signaling pathway	TAS Traceable Author Statement more info
Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation	NAS Non-traceable Author Statement more info	PubMed
Wnt signaling pathway, calcium modulating pathway	IMP Inferred from Mutant Phenotype more info	PubMed
Wnt signaling pathway, calcium modulating pathway	NAS Non-traceable Author Statement more info	PubMed
Wnt signaling pathway, planar cell polarity pathway	TAS Traceable Author Statement more info	PubMed
activation of GTPase activity	IEA Inferred from Electronic Annotation more info
activation of JUN kinase activity	IDA Inferred from Direct Assay more info	PubMed
activation of JUN kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
activation of MAPK activity	IDA Inferred from Direct Assay more info	PubMed
activation of protein kinase B activity	IDA Inferred from Direct Assay more info	PubMed
anterior/posterior axis specification, embryo	IEA Inferred from Electronic Annotation more info
atrial septum development	IEA Inferred from Electronic Annotation more info
axon guidance	ISS Inferred from Sequence or Structural Similarity more info
canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cartilage development	IEA Inferred from Electronic Annotation more info
cell fate commitment	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cellular protein localization	IDA Inferred from Direct Assay more info	PubMed
cellular response to calcium ion	IEP Inferred from Expression Pattern more info	PubMed
cellular response to interferon-gamma	IEP Inferred from Expression Pattern more info	PubMed
cellular response to lipopolysaccharide	IEP Inferred from Expression Pattern more info	PubMed
cellular response to retinoic acid	ISS Inferred from Sequence or Structural Similarity more info
cellular response to transforming growth factor beta stimulus	IEP Inferred from Expression Pattern more info	PubMed
cervix development	IEA Inferred from Electronic Annotation more info
chemoattraction of serotonergic neuron axon	IEA Inferred from Electronic Annotation more info
chemorepulsion of dopaminergic neuron axon	IEA Inferred from Electronic Annotation more info
cochlea morphogenesis	IEA Inferred from Electronic Annotation more info
convergent extension involved in axis elongation	IEA Inferred from Electronic Annotation more info
convergent extension involved in organogenesis	IEA Inferred from Electronic Annotation more info
embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic skeletal system development	IMP Inferred from Mutant Phenotype more info	PubMed
epithelial cell proliferation involved in mammary gland duct elongation	IEA Inferred from Electronic Annotation more info
epithelial to mesenchymal transition	IEP Inferred from Expression Pattern more info	PubMed
establishment of epithelial cell apical/basal polarity	IEA Inferred from Electronic Annotation more info
establishment of planar polarity	IEA Inferred from Electronic Annotation more info
excitatory synapse assembly	TAS Traceable Author Statement more info	PubMed
face development	IMP Inferred from Mutant Phenotype more info	PubMed
genitalia development	IMP Inferred from Mutant Phenotype more info	PubMed
heart looping	IEA Inferred from Electronic Annotation more info
hematopoietic stem cell proliferation	IDA Inferred from Direct Assay more info	PubMed
hindgut morphogenesis	IEA Inferred from Electronic Annotation more info
hypophysis morphogenesis	IEA Inferred from Electronic Annotation more info
inhibitory synapse assembly	TAS Traceable Author Statement more info	PubMed
keratinocyte differentiation	IEP Inferred from Expression Pattern more info	PubMed
lateral sprouting involved in mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
lens development in camera-type eye	ISS Inferred from Sequence or Structural Similarity more info	PubMed
lung development	IEA Inferred from Electronic Annotation more info
male gonad development	IEP Inferred from Expression Pattern more info	PubMed
mammary gland branching involved in thelarche	IEA Inferred from Electronic Annotation more info
melanocyte proliferation	IEA Inferred from Electronic Annotation more info
membrane organization	TAS Traceable Author Statement more info
mesenchymal-epithelial cell signaling	IEA Inferred from Electronic Annotation more info
mesodermal to mesenchymal transition involved in gastrulation	IEA Inferred from Electronic Annotation more info
midgut development	IEA Inferred from Electronic Annotation more info
negative regulation of BMP signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of axon extension involved in axon guidance	IEA Inferred from Electronic Annotation more info
negative regulation of canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of cell proliferation in midbrain	NAS Non-traceable Author Statement more info	PubMed
negative regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of fat cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of melanin biosynthetic process	IEA Inferred from Electronic Annotation more info
negative regulation of mesenchymal cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of prostatic bud formation	IEA Inferred from Electronic Annotation more info
negative regulation of synapse assembly	IEA Inferred from Electronic Annotation more info
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
non-canonical Wnt signaling pathway	TAS Traceable Author Statement more info	PubMed
non-canonical Wnt signaling pathway via JNK cascade	IEA Inferred from Electronic Annotation more info
notochord morphogenesis	IEA Inferred from Electronic Annotation more info
olfactory bulb interneuron development	ISS Inferred from Sequence or Structural Similarity more info
optic cup formation involved in camera-type eye development	ISS Inferred from Sequence or Structural Similarity more info	PubMed
paraxial mesoderm formation	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in axis elongation	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in axon guidance	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in cardiac muscle tissue morphogenesis	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in cardiac right atrium morphogenesis	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in gastrula mediolateral intercalation	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in midbrain dopaminergic neuron differentiation	TAS Traceable Author Statement more info	PubMed
planar cell polarity pathway involved in neural tube closure	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in outflow tract morphogenesis	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in pericardium morphogenesis	IEA Inferred from Electronic Annotation more info
planar cell polarity pathway involved in ventricular septum morphogenesis	IEA Inferred from Electronic Annotation more info
positive regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of T cell chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cartilage development	IEA Inferred from Electronic Annotation more info
positive regulation of cell-cell adhesion mediated by cadherin	IEA Inferred from Electronic Annotation more info
positive regulation of chemokine biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cytokine production involved in immune response	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of endocytosis	IEA Inferred from Electronic Annotation more info
positive regulation of endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of endothelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of fibroblast proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of heart induction by negative regulation of canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of interferon-gamma production	IEA Inferred from Electronic Annotation more info
positive regulation of interleukin-1 beta secretion	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of interleukin-1 beta secretion	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of interleukin-8 secretion	IEA Inferred from Electronic Annotation more info
positive regulation of macrophage activation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of macrophage cytokine production	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of meiotic nuclear division	IEA Inferred from Electronic Annotation more info
positive regulation of mesenchymal cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of neuron death	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neuron projection arborization	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of non-canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of ossification	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of peptidyl-serine phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of peptidyl-threonine phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of protein binding	IEA Inferred from Electronic Annotation more info
positive regulation of protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of protein kinase C activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein kinase C signaling	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein localization to synapse	TAS Traceable Author Statement more info	PubMed
positive regulation of response to cytokine stimulus	IDA Inferred from Direct Assay more info	PubMed
positive regulation of thymocyte apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of timing of anagen	IEA Inferred from Electronic Annotation more info
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-templated	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of tumor necrosis factor secretion	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of type I interferon-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
post-anal tail morphogenesis	IEA Inferred from Electronic Annotation more info
postsynapse assembly	TAS Traceable Author Statement more info	PubMed
presynapse assembly	TAS Traceable Author Statement more info	PubMed
primary heart field specification	IEA Inferred from Electronic Annotation more info
primitive streak formation	IEA Inferred from Electronic Annotation more info
regulation of I-kappaB kinase/NF-kappaB signaling	ISS Inferred from Sequence or Structural Similarity more info
regulation of branching involved in mammary gland duct morphogenesis	IEA Inferred from Electronic Annotation more info
regulation of cellular protein localization	IEA Inferred from Electronic Annotation more info
regulation of inflammatory response	NAS Non-traceable Author Statement more info	PubMed
regulation of postsynapse organization	IDA Inferred from Direct Assay more info	PubMed
regulation of postsynapse organization	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of postsynaptic cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
regulation of postsynaptic cytosolic calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of synapse organization	IDA Inferred from Direct Assay more info	PubMed
regulation of synapse organization	IMP Inferred from Mutant Phenotype more info	PubMed
response to organic substance	IEP Inferred from Expression Pattern more info	PubMed
secondary heart field specification	IEA Inferred from Electronic Annotation more info
secondary palate development	IMP Inferred from Mutant Phenotype more info	PubMed
somitogenesis	IEA Inferred from Electronic Annotation more info
type B pancreatic cell development	IEA Inferred from Electronic Annotation more info
urinary bladder development	IEA Inferred from Electronic Annotation more info
uterus development	IEA Inferred from Electronic Annotation more info
vagina development	IEA Inferred from Electronic Annotation more info
wound healing	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
Golgi lumen	TAS Traceable Author Statement more info
cell surface	IEA Inferred from Electronic Annotation more info
clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
clathrin-coated vesicle membrane	TAS Traceable Author Statement more info
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
endocytic vesicle membrane	TAS Traceable Author Statement more info
endoplasmic reticulum lumen	TAS Traceable Author Statement more info
extracellular exosome	TAS Traceable Author Statement more info
extracellular region	TAS Traceable Author Statement more info	PubMed
extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extracellular space	IDA Inferred from Direct Assay more info	PubMed
glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
postsynapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: protein Wnt-5a

Names: WNT-5A protein; epididymis secretory sperm binding protein; wingless-type MMTV integration site family, member 5A

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_031992.1 RefSeqGene

Range

5001..26928

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001256105.1 → NP_001243034.1 protein Wnt-5a isoform 2 precursor

See identical proteins and their annotated locations for NP_001243034.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1.

Source sequence(s)

AC121764, AK290869, BU742635, DB224740

Consensus CDS

CCDS58835.1

UniProtKB/Swiss-Prot

P41221

UniProtKB/TrEMBL

A0A024R316

Related

ENSP00000420104.1, ENST00000497027.5

Conserved Domains (1) summary

pfam00110
Location:60 → 365

wnt; wnt family
NM_001377271.1 → NP_001364200.1 protein Wnt-5a isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AC121764
NM_001377272.1 → NP_001364201.1 protein Wnt-5a isoform 2 precursor

Status: REVIEWED

Source sequence(s)

AC121764
NM_003392.7 → NP_003383.4 protein Wnt-5a isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AC121764, AK090582, BC064694, BU742635

Consensus CDS

CCDS46850.1

Related

ENSP00000264634.4, ENST00000264634.8