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
Gene location (Human) Chr. Chromosome 13 (human)[1] Band 13q34 Start 113,820,549 bp[1] End 113,864,076 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 A1.1|8 6.06 cM Start 13,465,374 bp[2] End 13,494,490 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding • receptor binding • receptor tyrosine kinase binding • voltage-gated calcium channel activity • receptor ligand activity • GO:0032947 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 binding, bridging Cellular component • endoplasmic reticulum lumen • cytoplasm • Golgi lumen • platelet alpha granule lumen • extracellular exosome • extracellular region • intracellular • extracellular Biological process • positive regulation of natural killer cell differentiation • apoptotic cell clearance • negative regulation of interleukin-1 secretion • cellular response to vitamin K • negative regulation of sequence-specific 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 • negative regulation of interleukin-6 secretion • positive regulation of phagocytosis • positive regulation of protein kinase B signaling • cell cycle arrest • 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 • 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 replication • cellular 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 • cellular response to drug • platelet aggregation • positive regulation of TOR signaling • peptidyl-serine phosphorylation • ER to Golgi vesicle-mediated transport • GO:0022415 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 modification • cellular protein metabolic process • protein localization to plasma membrane • regulation of 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: 13.47 – 13.49 Mb
PubMed search	[3]	[4]
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.[5]

Interactions

Gas6 has been shown to interact with AXL receptor tyrosine kinase, MerTK and TYRO3.[6][7]

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.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000183087 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031451 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: GAS6 growth arrest-specific 6".
6. Mark MR, Chen J, Hammonds RG, Sadick M, Godowsk PJ (Apr 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.
7. Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, Mizuno K (Nov 1996). "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.
8. Bellido-Martín, L; de Frutos, PG (2008). "Vitamin K-dependent actions of Gas6". Vitamins and hormones. 78: 185–209. doi:10.1016/S0083-6729(07)00009-X. PMID 18374195.

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. doi:10.1038/373623a0. PMID 7854420.
• 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. 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. 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.
• 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.
• 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.