P41221 (WNT5A_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 124. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Homo sapiens (Human) [Reference proteome]|
|Taxonomic identifier||9606 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo|
|Sequence length||380 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
Homooligomer; disulfide-linked, leading to inactivation. Interacts with PORCN. Interacts with WLS By similarity.
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). Ref.5
Palmitoylation is necessary for stimulation of cell migration, inhibition of the beta-catenin pathway and receptor binding By similarity.
Glycosylation is necessary for secretion but not for activity By similarity.
Palmitoylation at Ser-244 is required for efficient binding to frizzled receptors. It is also required for subsequent palmitoylation at Cys-104. Palmitoylation is necessary for proper trafficking to cell surface By similarity.
Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT5A By similarity.
|Involvement in disease|
Robinow syndrome autosomal dominant (DRS) [MIM:180700]: A 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.
Belongs to the Wnt family.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: P41221-1) |
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: P41221-2) |
The sequence of this isoform differs from the canonical sequence as follows:
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 35||35||Potential|
|Propeptide||36 – 61||26||By similarity||PRO_0000352796|
|Chain||62 – 380||319||Protein Wnt-5a||PRO_0000041427|
Amino acid modifications
|Lipidation||104||1||S-palmitoyl cysteine By similarity|
|Lipidation||244||1||O-palmitoyl serine; by PORCN By similarity|
|Glycosylation||114||1||N-linked (GlcNAc...) Potential|
|Glycosylation||120||1||N-linked (GlcNAc...) Potential|
|Glycosylation||312||1||N-linked (GlcNAc...) Potential|
|Glycosylation||326||1||N-linked (GlcNAc...) Potential|
|Alternative sequence||1 – 15||15||Missing in isoform 2.||VSP_035594|
|Natural variant||83||1||C → S in DRS; hypomorphic mutation. Ref.7||VAR_066623|
|Natural variant||182||1||C → R in DRS; hypomorphic mutation. Ref.7||VAR_066629|
|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.
|RefSeq||NP_001243034.1. NM_001256105.1. [P41221-2]|
NP_003383.2. NM_003392.4. [P41221-1]
XP_006713387.1. XM_006713324.1. [P41221-2]
3D structure databases
|SMR||P41221. Positions 94-309. |
Protein-protein interaction databases
|BioGrid||113311. 5 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENST00000264634; ENSP00000264634; ENSG00000114251. [P41221-1]|
ENST00000474267; ENSP00000417310; ENSG00000114251. [P41221-1]
ENST00000497027; ENSP00000420104; ENSG00000114251. [P41221-2]
|UCSC||uc003dhm.3. human. [P41221-1]|
|HGNC||HGNC:12784. WNT5A. |
|MIM||164975. gene. |
|Orphanet||3107. Autosomal dominant Robinow syndrome. |
Enzyme and pathway databases
|Reactome||REACT_111102. Signal Transduction. |
Gene expression databases
Family and domain databases
|InterPro||IPR005817. Wnt. |
|PANTHER||PTHR12027. PTHR12027. 1 hit. |
PTHR12027:SF33. PTHR12027:SF33. 1 hit.
|Pfam||PF00110. wnt. 1 hit. |
|PRINTS||PR01349. WNTPROTEIN. |
|SMART||SM00097. WNT1. 1 hit. |
|PROSITE||PS00246. WNT1. 1 hit. |
|ChiTaRS||WNT5A. human. |
|Accession||Primary (citable) accession number: P41221|
Secondary accession number(s): A8K4A4, Q6P278
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
|Disclaimer||Any 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.|
Index of protein domains and families
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
|Human polymorphisms and disease mutations|
Index of human polymorphisms and disease mutations
|Human entries with polymorphisms or disease mutations|
List of human entries with polymorphisms or disease mutations
|Human chromosome 3|
Human chromosome 3: entries, gene names and cross-references to MIM