GAS6

Growth arrest – specific 6, also known as GAS6, is a human gene coding for the GAS6 protein. It is similar to the Protein S with the same domain organization and 43% amino acid identity. It was originally found as a gene upregulated by growth arrested fibroblasts.

GAS6
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1H30, 2C5D, 4RA0
Identifiers
Aliases	GAS6, AXLLG, AXSF, growth arrest specific 6
External IDs	OMIM: 600441; MGI: 95660; HomoloGene: 638; GeneCards: GAS6; OMA:GAS6 - orthologs
Gene location (Human) Chr. Chromosome 13 (human) Band 13q34 Start 113,820,549 bp End 113,864,076 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8 A1.1|8 6.06 cM Start 13,515,374 bp End 13,544,490 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ascending aorta Descending thoracic aorta right uterine tube right coronary artery canal of the cervix apex of heart body of uterus left uterine tube popliteal artery tibial arteries Top expressed in stroma of bone marrow calvaria choroid plexus of fourth ventricle gallbladder ankle skin of external ear right kidney lip epithelium of stomach right lung More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding signaling receptor binding receptor tyrosine kinase binding voltage-gated calcium channel activity receptor ligand activity molecular adaptor activity phosphatidylserine binding metal ion binding protein tyrosine kinase activator activity calcium ion binding cysteine-type endopeptidase inhibitor activity involved in apoptotic process protein-macromolecule adaptor activity Cellular component endoplasmic reticulum lumen cytoplasm Golgi lumen platelet alpha granule lumen extracellular exosome extracellular region intracellular anatomical structure extracellular space Biological process positive regulation of natural killer cell differentiation apoptotic cell clearance cellular response to vitamin K negative regulation of DNA-binding transcription factor activity positive regulation of protein kinase activity negative regulation of biomineral tissue development negative regulation of tumor necrosis factor-mediated signaling pathway cellular response to starvation positive regulation of phagocytosis positive regulation of protein kinase B signaling positive regulation of cytokine-mediated signaling pathway positive regulation of gene expression dendritic cell differentiation neuron migration cell adhesion protein kinase B signaling positive regulation of glomerular filtration B cell chemotaxis negative regulation of apoptotic process positive regulation of ERK1 and ERK2 cascade phagocytosis regulation of growth activation of protein kinase B activity negative regulation of tumor necrosis factor production platelet degranulation viral entry into host cell negative regulation of oligodendrocyte apoptotic process leukocyte migration enzyme linked receptor protein signaling pathway positive regulation of protein tyrosine kinase activity cell migration platelet activation negative regulation of transcription, DNA-templated positive regulation of protein export from nucleus animal organ regeneration cellular response to growth factor stimulus negative regulation of interferon-gamma production macrophage cytokine production cellular response to glucose stimulus hematopoietic stem cell migration to bone marrow negative regulation of dendritic cell apoptotic process calcium ion transmembrane transport cell-substrate adhesion negative regulation of interleukin-6 production positive regulation of dendritic cell chemotaxis signal peptide processing viral genome replication cell population proliferation positive regulation of fibroblast proliferation negative regulation of cysteine-type endopeptidase activity involved in apoptotic process negative regulation of fibroblast apoptotic process positive regulation of peptidyl-serine phosphorylation platelet aggregation positive regulation of TOR signaling peptidyl-serine phosphorylation endoplasmic reticulum to Golgi vesicle-mediated transport viral process extracellular matrix assembly cellular response to interferon-alpha protein phosphorylation negative regulation of renal albumin absorption negative regulation of endothelial cell apoptotic process positive regulation of protein phosphorylation signal transduction blood coagulation apoptotic process post-translational protein modification protein localization to plasma membrane regulation of signaling receptor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2621 14456 Ensembl ENSG00000183087 ENSMUSG00000031451 UniProt Q14393 Q61592 RefSeq (mRNA) NM_001143946 NM_000820 NM_001143945 NM_019521 RefSeq (protein) NP_000811 NP_062394 Location (UCSC) Chr 13: 113.82 – 113.86 Mb Chr 8: 13.52 – 13.54 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

Gas6 is a gamma-carboxyglutamic acid (Gla) domain-containing protein thought to be involved in the stimulation of cell proliferation.

Interactions

Gas6 has been shown to interact with AXL receptor tyrosine kinase, MerTK and TYRO3.

The presence of Gla needs a vitamin K-dependent enzymatic reaction that carboxylates the gamma carbon of certain glutamic residues of the protein during its production in the endoplasmic reticulum. The action of vitamin K is essential on GAS6 function.

Further reading

• Maree AO, Jneid H, Palacios IF, Rosenfield K, MacRae CA, Fitzgerald DJ (2007). "Growth arrest specific gene (GAS) 6 modulates platelet thrombus formation and vascular wall homeostasis and represents an attractive drug _target". Curr. Pharm. Des. 13 (26): 2656–61. doi:10.2174/138161207781662948. PMID 17897008.
• Varnum BC, Young C, Elliott G, Garcia A, Bartley TD, Fridell YW, Hunt RW, Trail G, Clogston C, Toso RJ (1995). "Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6". Nature. 373 (6515): 623–6. Bibcode:1995Natur.373..623V. doi:10.1038/373623a0. PMID 7854420. S2CID 4242251.
• Stitt TN, Conn G, Gore M, Lai C, Bruno J, Radziejewski C, Mattsson K, Fisher J, Gies DR, Jones PF (1995). "The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases". Cell. 80 (4): 661–70. doi:10.1016/0092-8674(95)90520-0. PMID 7867073.
• Manfioletti G, Brancolini C, Avanzi G, Schneider C (1993). "The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade". Mol. Cell. Biol. 13 (8): 4976–85. doi:10.1128/MCB.13.8.4976. PMC 360142. PMID 8336730.
• Saccone S, Marcandalli P, Gostissa M, Schneider C, Della Valle G (1996). "Assignment of the human GAS6 gene to chromosome 13q34 by fluorescence in situ hybridization". Genomics. 30 (1): 129–31. doi:10.1006/geno.1995.0027. PMID 8595896.
• Li R, Chen J, Hammonds G, Phillips H, Armanini M, Wood P, Bunge R, Godowski PJ, Sliwkowski MX, Mather JP (1996). "Identification of Gas6 as a growth factor for human Schwann cells". J. Neurosci. 16 (6): 2012–9. doi:10.1523/JNEUROSCI.16-06-02012.1996. PMC 6578513. PMID 8604045.
• Mark MR, Chen J, Hammonds RG, Sadick M, Godowsk PJ (1996). "Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl". J. Biol. Chem. 271 (16): 9785–9. doi:10.1074/jbc.271.16.9785. PMID 8621659.
• Goruppi S, Ruaro E, Schneider C (1996). "Gas6, the ligand of Axl tyrosine kinase receptor, has mitogenic and survival activities for serum starved NIH3T3 fibroblasts". Oncogene. 12 (3): 471–80. PMID 8637702.
• Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, Mizuno K (1997). "Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases". J. Biol. Chem. 271 (47): 30022–7. doi:10.1074/jbc.271.47.30022. PMID 8939948.
• Loeser RF, Varnum BC, Carlson CS, Goldring MB, Liu ET, Sadiev S, Kute TE, Wallin R (1997). "Human chondrocyte expression of growth-arrest-specific gene 6 and the tyrosine kinase receptor axl: potential role in autocrine signaling in cartilage". Arthritis Rheum. 40 (8): 1455–65. doi:10.1002/art.1780400814. PMID 9259426.
• Marcandalli P, Gostissa M, Varnum B, Goruppi S, Schneider C (1997). "Identification and tissue expression of a splice variant for the growth arrest-specific gene gas6". FEBS Lett. 415 (1): 56–8. Bibcode:1997FEBSL.415...56M. doi:10.1016/S0014-5793(97)01094-6. PMID 9326368.
• Goruppi S, Yamane H, Marcandalli P, Garcia A, Clogston C, Gostissa M, Varnum B, Schneider C (1997). "The product of a gas6 splice variant allows the release of the domain responsible for Axl tyrosine kinase receptor activation". FEBS Lett. 415 (1): 59–63. Bibcode:1997FEBSL.415...59G. doi:10.1016/S0014-5793(97)01093-4. PMID 9326369.
• Nakano T, Ishimoto Y, Kishino J, Umeda M, Inoue K, Nagata K, Ohashi K, Mizuno K, Arita H (1997). "Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6". J. Biol. Chem. 272 (47): 29411–4. doi:10.1074/jbc.272.47.29411. PMID 9367994.
• Prieto AL, Weber JL, Lai C (2000). "Expression of the receptor protein-tyrosine kinases Tyro-3, Axl, and mer in the developing rat central nervous system". J. Comp. Neurol. 425 (2): 295–314. doi:10.1002/1096-9861(20000918)425:2<295::AID-CNE11>3.0.CO;2-G. PMID 10954847. S2CID 868501.
• Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F, Arnout J, Dewerchin M, Hoylaerts M, Herbert J, Collen D, Dahlbäck B, Carmeliet P (2001). "Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis". Nat. Med. 7 (2): 215–21. doi:10.1038/84667. PMID 11175853. S2CID 10502090.
• Sun WS, Misao R, Iwagaki S, Fujimoto J, Tamaya T (2003). "Coexpression of growth arrest-specific gene 6 and receptor tyrosine kinases, Axl and Sky, in human uterine endometrium and ovarian endometriosis". Mol. Hum. Reprod. 8 (6): 552–8. doi:10.1093/molehr/8.6.552. PMID 12029073.
• Sasaki T, Knyazev PG, Cheburkin Y, Göhring W, Tisi D, Ullrich A, Timpl R, Hohenester E (2003). "Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains". J. Biol. Chem. 277 (46): 44164–70. doi:10.1074/jbc.M207340200. PMID 12218057.
• Ito M, Nakashima M, Nakayama T, Ohtsuru A, Nagayama Y, Takamura N, Demedchik EP, Sekine I, Yamashita S (2003). "Expression of receptor-type tyrosine kinase, Axl, and its ligand, Gas6, in pediatric thyroid carcinomas around chernobyl". Thyroid. 12 (11): 971–5. doi:10.1089/105072502320908303. PMID 12490074.
• Shankar SL, O'Guin K, Cammer M, McMorris FA, Stitt TN, Basch RS, Varnum B, Shafit-Zagardo B (2003). "The growth arrest-specific gene product Gas6 promotes the survival of human oligodendrocytes via a phosphatidylinositol 3-kinase-dependent pathway". J. Neurosci. 23 (10): 4208–18. doi:10.1523/JNEUROSCI.23-10-04208.2003. PMC 6741089. PMID 12764109.