GAS6

Growth arrest-specific 6

PDB rendering based on 1h30.

Available structures
PDB	1H30, 2C5D

Identifiers

Symbols

GAS6; AXLLG; AXSF; DKFZp666G247; FLJ34709

External IDs

OMIM: 600441 MGI: 95660 HomoloGene: 638 GeneCards: GAS6 Gene

Gene Ontology
Molecular function	• receptor binding • calcium ion binding • receptor agonist activity
Cellular component	• extracellular region • extracellular space • endoplasmic reticulum lumen • Golgi lumen • platelet alpha granule lumen
Biological process	• platelet degranulation • proteolysis • signal transduction • blood coagulation • cell proliferation • peptidyl-glutamic acid carboxylation • platelet activation • regulation of growth • post-translational protein modification • cellular protein metabolic process • positive regulation of fibroblast proliferation • leukocyte migration • positive regulation of ERK1 and ERK2 cascade
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 13:
114.52 – 114.57 Mb

Chr 8:
13.47 – 13.49 Mb

PubMed search

[1]

[2]

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 is a gamma-carboxyglutamic acid (Gla) domain-containing protein thought to be involved in the stimulation of cell proliferation^[1]

Interactions

GAS6 has been shown to interact with AXL receptor tyrosine kinase, MerTK and TYRO3.^[2]^[3]

References

^ "Entrez Gene: GAS6 growth arrest-specific 6". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2621.
^ Mark, M R; Chen J, Hammonds R G, Sadick M, Godowsk P J (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. (UNITED STATES) 271 (16): 9785–9. doi:10.1074/jbc.271.16.9785. ISSN 0021-9258. PMID 8621659.
^ 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. (UNITED STATES) 271 (47): 30022–7. doi:10.1074/jbc.271.47.30022. ISSN 0021-9258. PMID 8939948.

Maree AO, Jneid H, Palacios IF, et al. (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, et al. (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, et al. (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. PMC 360142. PMID 8336730. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=360142.
Saccone S, Marcandalli P, Gostissa M, et al. (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, et al. (1996). "Identification of Gas6 as a growth factor for human Schwann cells". J. Neurosci. 16 (6): 2012–9. PMID 8604045.
Mark MR, Chen J, Hammonds RG, et al. (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, et al. (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, et al. (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:10.1002/1529-0131(199708)40:8<1455::AID-ART14>3.0.CO;2-B. PMID 9259426.
Marcandalli P, Gostissa M, Varnum B, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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, et al. (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.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Ito M, Nakashima M, Nakayama T, et al. (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, et al. (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. PMID 12764109.

PDB gallery

1h30: C-TERMINAL LG DOMAIN PAIR OF HUMAN GAS6

2c5d: STRUCTURE OF A MINIMAL GAS6-AXL COMPLEX

GAS6

Interactions

References

Further reading