ANKS1A

{{Short description|Protein-coding gene in the species Homo sapiens}}

Ankyrin repeat and SAM domain-containing protein 1A (ANKS1A), also known as ODIN, is a protein that in humans is encoded by the ANKS1A gene on chromosome 6.{{cite journal | vauthors = Nagase T, Seki N, Ishikawa K, Ohira M, Kawarabayasi Y, Ohara O, Tanaka A, Kotani H, Miyajima N, Nomura N | title = Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain | journal = DNA Research | volume = 3 | issue = 5 | pages = 321–9, 341–54 | date = October 1996 | pmid = 9039502 | doi = 10.1093/dnares/3.5.321 | doi-access = free }}{{cite web | title = Entrez Gene: ANKS1A ankyrin repeat and sterile alpha motif domain containing 1A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23294}}

It is ubiquitously expressed in many tissues and cell types.{{Cite web|url=http://biogps.org/gene/22808/|title=BioGPS - your Gene Portal System|website=biogps.org|access-date=2016-10-10}}{{Dead link|date=September 2018 |bot=InternetArchiveBot |fix-attempted=yes }} ODIN is known to regulate the epidermal growth factor receptor (EGFR) and EphA receptor signaling pathways.{{cite journal | vauthors = Kristiansen TZ, Nielsen MM, Blagoev B, Pandey A, Mann M | title = Mouse embryonic fibroblasts derived from Odin deficient mice display a hyperproliiferative phenotype | journal = DNA Research | volume = 11 | issue = 4 | pages = 285–92 | date = August 2004 | pmid = 15500253 }} As a Src family kinase target, ODIN has been implicated in the development of cancer.{{cite journal | vauthors = Emaduddin M, Edelmann MJ, Kessler BM, Feller SM | title = Odin (ANKS1A) is a Src family kinase target in colorectal cancer cells | journal = Cell Communication and Signaling | volume = 6 | pages = 7 | date = 2008-01-01 | pmid = 18844995 | doi = 10.1186/1478-811X-6-7 | pmc=2584000 | doi-access = free }} The ANKS1A gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.{{cite journal | vauthors = Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, Nordio F, Hyde CL, Cannon CP, Sacks FM, Poulter NR, Sever PS, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS | title = Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials | journal = Lancet | volume = 385 | issue = 9984 | pages = 2264–71 | date = June 2015 | pmid = 25748612 | doi = 10.1016/S0140-6736(14)61730-X | pmc=4608367}}

Structure

= Gene =

The ANKS1A gene resides on chromosome 6 at the band 6p21.31 and includes 29 exons. This gene produces 2 isoforms through alternative splicing.{{Cite web|url=https://www.uniprot.org/uniprot/Q92625|title=ANKS1A - Ankyrin repeat and SAM domain-containing protein 1A - Homo sapiens (Human) - ANKS1A gene & protein|website=www.uniprot.org|access-date=2016-10-10}}

= Protein =

ODIN is a member of the ankyrin repeat and sterile alpha motif domain-containing (ANKS) family and contains 6 ankyrin repeats, 1 phosphotyrosine binding (PTD) domain, and 2 tandem sterile alpha motif (SAM) domains.{{cite journal | vauthors = Mercurio FA, Marasco D, Pirone L, Pedone EM, Pellecchia M, Leone M | title = Solution structure of the first Sam domain of Odin and binding studies with the EphA2 receptor | journal = Biochemistry | volume = 51 | issue = 10 | pages = 2136–45 | date = March 2012 | pmid = 22332920 | doi = 10.1021/bi300141h | pmc=3319784}} The first SAM domain binds to the SAM domain of the EphA2 receptor by adopting a mid-loop/end-helix conformation and may regulate EphA2 endocytosis.{{cite journal | vauthors = Mercurio FA, Di Natale C, Pirone L, Scognamiglio PL, Marasco D, Pedone EM, Saviano M, Leone M | title = Peptide Fragments of Odin-Sam1: Conformational Analysis and Interaction Studies with EphA2-Sam | journal = ChemBioChem | volume = 16 | issue = 11 | pages = 1629–36 | date = July 2015 | pmid = 26120079 | doi = 10.1002/cbic.201500197 | s2cid = 24673174 }}

Function

ODIN is widely expressed in tissues including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.{{cite journal | vauthors = Pandey A, Blagoev B, Kratchmarova I, Fernandez M, Nielsen M, Kristiansen TZ, Ohara O, Podtelejnikov AV, Roche S, Lodish HF, Mann M | title = Cloning of a novel phosphotyrosine binding domain containing molecule, Odin, involved in signaling by receptor tyrosine kinases | journal = Oncogene | volume = 21 | issue = 52 | pages = 8029–36 | date = November 2002 | pmid = 12439753 | doi = 10.1038/sj.onc.1205988 | doi-access = free }} ODIN has been identified as one of the tyrosine phosphorylated proteins induced by activating epidermal growth factor or platelet-derived growth factor receptor tyrosine kinases. ODIN is involved in negative regulation of the EGFR signaling pathway. It is reported that ODIN level is correlated with the degree of increased EGF-induced EGFR trafficking to recycle endosomes and recycle back to the cell surface, suggesting a role in EGFR recycling.{{cite journal | vauthors = Tong J, Sydorskyy Y, St-Germain JR, Taylor P, Tsao MS, Moran MF | title = Odin (ANKS1A) modulates EGF receptor recycling and stability | journal = PLOS ONE | volume = 8 | issue = 6 | pages = e64817 | date = 2013-01-01 | pmid = 23825523 | doi = 10.1371/journal.pone.0064817 | pmc=3692516| bibcode = 2013PLoSO...864817T | doi-access = free }} Furthermore, ODIN serves as a key adaptor protein regulating the EphA receptor signaling pathway, which is critical for regulating EphA8-mediated cell migration and neurite outgrowth.{{cite journal | vauthors = Kim J, Lee H, Kim Y, Yoo S, Park E, Park S | title = The SAM domains of Anks family proteins are critically involved in modulating the degradation of EphA receptors | journal = Molecular and Cellular Biology | volume = 30 | issue = 7 | pages = 1582–92 | date = April 2010 | pmid = 20100865 | doi = 10.1128/MCB.01605-09 | pmc=2838079}}{{cite journal | vauthors = Shin J, Gu C, Park E, Park S | title = Identification of phosphotyrosine binding domain-containing proteins as novel downstream targets of the EphA8 signaling function | journal = Molecular and Cellular Biology | volume = 27 | issue = 23 | pages = 8113–26 | date = December 2007 | pmid = 17875921 | doi = 10.1128/MCB.00794-07 | pmc=2169194}} It has been demonstrated that deletion of the phosphotyrosine binding domain in ODIN will lead to an immaturely developed subcommissural organ (SCO) with a severe midbrain hydrocephalic phenotype, which means ODIN also plays a role in the proper development of the SCO and in ependymal cells in the cerebral aqueduct.{{cite journal | vauthors = Park S, Lee H, Park S | title = In Vivo Expression of the PTB-deleted Odin Mutant Results in Hydrocephalus | journal = Molecules and Cells | volume = 38 | issue = 5 | pages = 426–31 | date = May 2015 | pmid = 26018557 | doi = 10.14348/molcells.2015.2288 | pmc=4443284}}

Clinical significance

As a novel target of Src family kinases, which are implicated in the development of some colorectal cancers, ODIN may be involved in cancer cell signaling mechanisms.{{cite journal | vauthors = Emaduddin M, Edelmann MJ, Kessler BM, Feller SM | title = Odin (ANKS1A) is a Src family kinase target in colorectal cancer cells | journal = Cell Communication and Signaling | volume = 6 | pages = 7 | date = October 2008 | pmid = 18844995 | doi = 10.1186/1478-811X-6-7 | pmc=2584000 | doi-access = free }} In a study, 64 colorectal cancer cell lines were tested for their expression of Lck. Mass spectrometric analyses of Lck-purified proteins subsequently identified several proteins readily known as SFK kinase substrates, including cortactin, Tom1L1 (SRCASM), GIT1, vimentin and AFAP1L2 (XB130). Additional proteins previously reported as substrates of other tyrosine kinases were also detected, including ODIN. ODIN was further analyzed and found to contain substantially less pY upon inhibition of SFK activity in SW620 cells, indicating that it is a formerly unknown SFK target in colorectal carcinoma cells. Furthermore, it has been found that ODIN regulates COPII-mediated anterograde transport of receptor tyrosine kinases, which is a critical mechanism in the process of tumor genesis.{{cite journal | vauthors = Lee H, Noh H, Mun J, Gu C, Sever S, Park S | title = Anks1a regulates COPII-mediated anterograde transport of receptor tyrosine kinases critical for tumorigenesis | journal = Nature Communications | volume = 7 | pages = 12799 | date = September 2016 | pmid = 27619642 | doi = 10.1038/ncomms12799 | pmc=5027278| bibcode = 2016NatCo...712799L }}

= Clinical marker =

A multi-locus genetic risk score study based on a combination of 27 loci, including the ANKS1A gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).

References

External links

{{UCSC gene info|ANKS1A}}
{{PDBe-KB2|Q92625|Human Ankyrin repeat and SAM domain-containing protein 1A}}
{{PDBe-KB2|P59672|Mouse Ankyrin repeat and SAM domain-containing protein 1A}}