Tyrosine-protein kinase Yes (YES1)

The protein contains 543 amino acids for an estimated molecular weight of 60801 Da.

 

Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGRF, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis. (updated: Oct. 10, 2018)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  2. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 74%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs34580680
dbSNP:rs35126906

The reference OMIM entry for this protein is 164880

V-yes-1 yamaguchi sarcoma viral oncogene; yes1
Oncogene yes1
Yamaguchi sarcoma oncogene

DESCRIPTION

The YES1 oncogene is homologous to the v-yes gene of the Yamaguchi sarcoma virus. The v-yes gene product is associated with tyrosine-specific protein kinase activity, and its amino acid sequence shows a high degree of homology with that of the v-src gene product of Rous sarcoma virus (see SRC; 190090) (summary by Semba et al., 1985).

CLONING

Using Northern blot analysis, Semba et al. (1985) found variable expression of a 4.8-kb RNA related to v-yes in human embryonic fibroblasts, 3 human cell lines, placenta, and fetal lung, liver, and kidney. Using a probe prepared from human YES2, a processed pseudogene, Sukegawa et al. (1987) cloned human YES1 from an embryonic fibroblast cDNA library. The deduced 543-amino acid protein has a calculated molecular mass of 60.8 kD. It has a putative kinase domain, conserved ATP-binding residues (lys305 and a GxGxxG motif at residue 284), a putative autophosphorylation site (tyr416), and a putative myristoylation site (gly2). Amino acids 91 through 543 of human YES1, including the kinase domain, share 96% identity with the corresponding region of v-yes. Oh et al. (2002) reported that the deduced 541-amino acid YES1 protein contains an SRC homology-3 (SH3) domain, followed by an SH2 domain and a C-terminal protein tyrosine kinase domain.

GENE FUNCTION

Using a yeast 2-hybrid assay of a HeLa cell library, Oh et al. (2002) showed that YES1 interacted with QM (RPL10; 312173). Immunoprecipitation analysis and protein pull-down assays showed that QM interacted with the SH3 domain of YES1. Full-length QM suppressed the kinase activity of YES1 by suppressing its autophosphorylation activity. Overexpression of QM resulted in increased YES1 mRNA and protein expression. Taniguchi et al. (2015) showed in mice and human cells that GP130 (600694), a coreceptor for IL6 (147620) cytokines, triggers activation of YAP (606608) and Notch (190198), transcriptional regulators that control tissue growth and regeneration, independently of the GP130 effector STAT3 (102582). Through YAP and Notch, intestinal GP130 signaling stimulates epithelial cell proliferation, causes aberrant differentiation, and confers resistance to mucosal erosion. GP130 associates with the related tyrosine kinases SRC (190090) and YES, which are activated on receptor engagement to phosphorylate YAP and induce its stabilization and nuclear translocation. This signaling module is strongly activated upon mucosal injury to promote healing and maintain barrier function.

GENE STRUCTURE

Sukegawa et al. (1987) found that the upstream region of the YES1 gene is GC rich.

MAPPING

Semba et al. (1985) found in DNA from human embryo fibroblasts 10 EcoRI fragments that hybridized with the Yamaguchi sarcoma virus oncogene. By a study of human-mouse cell hybrids, 4 of these fragments, designated YES1, were assigned to chromosome 18, and 1 fragment, designated YES2, was assigned to chromosome 6. (YES2 was later found by Semba et al. (1988) to be a pseudogene of YES1 and to be located at chromosome 22q11.2. Semba et al. (1988) stated: 'The failure of proper mapping in our earlier experiment might have been caused by instability of hybrid cell clones.') The other 5 fragments could not be mapped either because hybridization signals were too weak or differentiation from mouse Yes fragments was impossible. There was evidence for multiple copies of YES-related genes in the human genome. At least 3 of the human ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 164880 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).