GAS6_HUMAN
ID GAS6_HUMAN Reviewed; 678 AA.
AC Q14393; B3KRQ7; B3KVL4; E9PBL7; Q6IMN1; Q7Z7N3;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 12-SEP-2018, sequence version 3.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Growth arrest-specific protein 6 {ECO:0000305};
DE Short=GAS-6;
DE AltName: Full=AXL receptor tyrosine kinase ligand;
DE Flags: Precursor;
GN Name=GAS6 {ECO:0000312|HGNC:HGNC:4168}; Synonyms=AXLLG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX PubMed=8336730; DOI=10.1128/mcb.13.8.4976-4985.1993;
RA Manfioletti G., Brancolini C., Avanzi G., Schneider C.;
RT "The protein encoded by a growth arrest-specific gene (gas6) is a new
RT member of the vitamin K-dependent proteins related to protein S, a negative
RT coregulator in the blood coagulation cascade.";
RL Mol. Cell. Biol. 13:4976-4985(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=15108283; DOI=10.1002/humu.20025;
RA Munoz X., Sumoy L., Ramirez-Lorca R., Villar J., de Frutos P.G., Sala N.;
RT "Human vitamin K-dependent GAS6: gene structure, allelic variation, and
RT association with stroke.";
RL Hum. Mutat. 23:506-512(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5).
RC TISSUE=Kidney, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-41; TYR-231; MET-347;
RP ARG-500; LEU-580; LYS-612 AND GLN-616.
RG SeattleSNPs variation discovery resource;
RL Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Fetal lung, and Fetal spleen;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-85.
RA Maree A.O., Hillmann A., McRedmond J.P., Fitzgerald D.J.;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP RECEPTOR INTERACTION.
RX PubMed=7854420; DOI=10.1038/373623a0;
RA Varnum B.C., Young C., Elliott G., Garcia A., Bartley T.D., Fridell Y.W.,
RA Hunt R.W., Trail G., Clogston C., Toso R.J., Yanagihara D., Bennett L.,
RA Silber M., Merewether L.A., Tseng A., Escobar E., Liu E.T., Yamane H.K.;
RT "Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein
RT encoded by growth-arrest-specific gene 6.";
RL Nature 373:623-626(1995).
RN [9]
RP RECEPTOR INTERACTION.
RX PubMed=7867073; DOI=10.1016/0092-8674(95)90520-0;
RA Stitt T.N., Conn G., Gore M., Lai C., Bruno J., Radziejewski C.,
RA Mattsson K., Fisher J., Gies D.R., Jones P.F., Masiakowski P., Ryan T.E.,
RA Tobkes N.J., Chen D.H., DiStefano P.S., Long G.L., Basilico C.,
RA Goldfarb M.P., Lemke G., Glass D.J., Yancopoulos G.D.;
RT "The anticoagulation factor protein S and its relative, Gas6, are ligands
RT for the Tyro 3/Axl family of receptor tyrosine kinases.";
RL Cell 80:661-670(1995).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=9326368; DOI=10.1016/s0014-5793(97)01094-6;
RA Marcandalli P., Gostissa M., Varnum B., Goruppi S., Schneider C.;
RT "Identification and tissue expression of a splice variant for the growth
RT arrest-specific gene gas6.";
RL FEBS Lett. 415:56-58(1997).
RN [11]
RP RECEPTOR INTERACTION.
RX PubMed=8939948; DOI=10.1074/jbc.271.47.30022;
RA Nagata K., Ohashi K., Nakano T., Arita H., Zong C., Hanafusa H., Mizuno K.;
RT "Identification of the product of growth arrest-specific gene 6 as a common
RT ligand for Axl, Sky, and Mer receptor tyrosine kinases.";
RL J. Biol. Chem. 271:30022-30027(1996).
RN [12]
RP RECEPTOR INTERACTION, SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING.
RX PubMed=9326369; DOI=10.1016/s0014-5793(97)01093-4;
RA Goruppi S., Yamane H., Marcandalli P., Garcia A., Clogston C., Gostissa M.,
RA Varnum B., Schneider C.;
RT "The product of a gas6 splice variant allows the release of the domain
RT responsible for Axl tyrosine kinase receptor activation.";
RL FEBS Lett. 415:59-63(1997).
RN [13]
RP FUNCTION OF THE GAS6/AXL SIGNALING PATHWAY.
RX PubMed=12364394; DOI=10.1161/01.res.0000036753.50601.e9;
RA D'Arcangelo D., Gaetano C., Capogrossi M.C.;
RT "Acidification prevents endothelial cell apoptosis by Axl activation.";
RL Circ. Res. 91:E4-12(2002).
RN [14]
RP FUNCTION OF THE GAS6/AXL SIGNALING PATHWAY.
RX PubMed=18840707; DOI=10.1182/blood-2008-05-157073;
RA Park I.K., Giovenzana C., Hughes T.L., Yu J., Trotta R., Caligiuri M.A.;
RT "The Axl/Gas6 pathway is required for optimal cytokine signaling during
RT human natural killer cell development.";
RL Blood 113:2470-2477(2009).
RN [15]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=21501828; DOI=10.1016/j.chom.2011.03.012;
RA Morizono K., Xie Y., Olafsen T., Lee B., Dasgupta A., Wu A.M., Chen I.S.;
RT "The soluble serum protein Gas6 bridges virion envelope phosphatidylserine
RT to the TAM receptor tyrosine kinase Axl to mediate viral entry.";
RL Cell Host Microbe 9:286-298(2011).
RN [16]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=23084921; DOI=10.1016/j.chom.2012.08.009;
RA Meertens L., Carnec X., Lecoin M.P., Ramdasi R., Guivel-Benhassine F.,
RA Lew E., Lemke G., Schwartz O., Amara A.;
RT "The TIM and TAM families of phosphatidylserine receptors mediate dengue
RT virus entry.";
RL Cell Host Microbe 12:544-557(2012).
RN [17]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=17005688; DOI=10.1128/jvi.01157-06;
RA Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T.,
RA Jones S., Feldmann H., Kawaoka Y.;
RT "Tyro3 family-mediated cell entry of Ebola and Marburg viruses.";
RL J. Virol. 80:10109-10116(2006).
RN [18]
RP PHOSPHORYLATION AT SER-71.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 261-678, MUTAGENESIS OF PHE-487;
RP LEU-620 AND TYR-660, AND INTERACTION WITH AXL.
RX PubMed=8621659; DOI=10.1074/jbc.271.16.9785;
RA Mark M.R., Chen J., Hammonds R.G., Sadick M., Godowski P.J.;
RT "Characterization of Gas6, a member of the superfamily of G domain-
RT containing proteins, as a ligand for Rse and Axl.";
RL J. Biol. Chem. 271:9785-9789(1996).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 261-678 IN COMPLEX WITH AXL,
RP SUBUNIT, GLYCOSYLATION AT ASN-420, AND MUTAGENESIS OF ARG-310 AND LYS-312.
RX PubMed=16362042; DOI=10.1038/sj.emboj.7600912;
RA Sasaki T., Knyazev P.G., Clout N.J., Cheburkin Y., Goehring W., Ullrich A.,
RA Timpl R., Hohenester E.;
RT "Structural basis for Gas6-Axl signalling.";
RL EMBO J. 25:80-87(2006).
CC -!- FUNCTION: Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and
CC MER whose signaling is implicated in cell growth and survival, cell
CC adhesion and cell migration. GAS6/AXL signaling plays a role in various
CC processes such as endothelial cell survival during acidification by
CC preventing apoptosis, optimal cytokine signaling during human natural
CC killer cell development, hepatic regeneration, gonadotropin-releasing
CC hormone neuron survival and migration, platelet activation, or
CC regulation of thrombotic responses. {ECO:0000269|PubMed:12364394,
CC ECO:0000269|PubMed:18840707}.
CC -!- FUNCTION: (Microbial infection) Can bridge virus envelope
CC phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate
CC viral entry by apoptotic mimicry (PubMed:21501828). Plays a role in
CC Dengue cell entry by apoptotic mimicry (PubMed:23084921). Plays a role
CC in Vaccinia virus cell entry by apoptotic mimicry (PubMed:21501828).
CC Plays a role in ebolavirus and marburgvirus cell entry by apoptotic
CC mimicry (PubMed:17005688). {ECO:0000269|PubMed:17005688,
CC ECO:0000269|PubMed:21501828, ECO:0000269|PubMed:23084921}.
CC -!- SUBUNIT: Heterodimer and heterotetramer with AXL.
CC {ECO:0000269|PubMed:16362042}.
CC -!- INTERACTION:
CC Q14393-1; P30530: AXL; NbExp=8; IntAct=EBI-20753849, EBI-2850927;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9326369}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q14393-2; Sequence=Displayed;
CC Name=2; Synonyms=gas6SV {ECO:0000303|PubMed:9326368};
CC IsoId=Q14393-1; Sequence=VSP_059770;
CC Name=3;
CC IsoId=Q14393-3; Sequence=VSP_059769;
CC Name=4;
CC IsoId=Q14393-4; Sequence=VSP_059768;
CC Name=5;
CC IsoId=Q14393-5; Sequence=VSP_059767;
CC -!- TISSUE SPECIFICITY: Plasma. Isoform 1 and isoform 2 are widely
CC expressed, isoform 1 being expressed at higher levels than isoform 2 in
CC most tissues. Isoform 2 is the predominant form in spleen.
CC {ECO:0000269|PubMed:8336730, ECO:0000269|PubMed:9326368}.
CC -!- PTM: [Isoform 2]: Proteolytically processed after secretion to yield a
CC N-terminal 36 kDa protein and a C-terminal 50 kDa protein including the
CC laminin G-like domains which activates AXL.
CC {ECO:0000269|PubMed:9326369}.
CC -!- PTM: Gamma-carboxyglutamate residues are formed by vitamin K dependent
CC carboxylation. These residues are essential for the binding of calcium.
CC {ECO:0000255|PROSITE-ProRule:PRU00463}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/gas6/";
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DR EMBL; L13720; AAA58494.1; -; mRNA.
DR EMBL; AY256843; AAO84057.1; -; Genomic_DNA.
DR EMBL; AY256830; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256831; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256832; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256833; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256834; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256835; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256836; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256837; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256838; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256839; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256840; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256841; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AY256842; AAO84057.1; JOINED; Genomic_DNA.
DR EMBL; AK092028; BAG52469.1; -; mRNA.
DR EMBL; AK122969; BAG53826.1; -; mRNA.
DR EMBL; AK126533; BAC86580.1; -; mRNA.
DR EMBL; AK290803; BAF83492.1; -; mRNA.
DR EMBL; EF631974; ABR09277.1; -; Genomic_DNA.
DR EMBL; BX072579; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC038984; AAH38984.1; -; mRNA.
DR EMBL; AY170372; AAO41859.1; -; Genomic_DNA.
DR EMBL; BK001240; DAA01155.1; -; Genomic_DNA.
DR CCDS; CCDS45072.1; -. [Q14393-2]
DR PIR; B48089; B48089.
DR RefSeq; NP_000811.1; NM_000820.3. [Q14393-2]
DR PDB; 1H30; X-ray; 2.20 A; A=261-678.
DR PDB; 2C5D; X-ray; 3.30 A; A/B=261-678.
DR PDB; 4RA0; X-ray; 3.07 A; A/B=279-678.
DR PDB; 5VXZ; X-ray; 2.30 A; A/B=281-675.
DR PDBsum; 1H30; -.
DR PDBsum; 2C5D; -.
DR PDBsum; 4RA0; -.
DR PDBsum; 5VXZ; -.
DR AlphaFoldDB; Q14393; -.
DR SMR; Q14393; -.
DR BioGRID; 108891; 136.
DR IntAct; Q14393; 34.
DR MINT; Q14393; -.
DR STRING; 9606.ENSP00000331831; -.
DR BindingDB; Q14393; -.
DR GlyGen; Q14393; 1 site.
DR iPTMnet; Q14393; -.
DR PhosphoSitePlus; Q14393; -.
DR BioMuta; GAS6; -.
DR DMDM; 48427995; -.
DR EPD; Q14393; -.
DR jPOST; Q14393; -.
DR MassIVE; Q14393; -.
DR MaxQB; Q14393; -.
DR PeptideAtlas; Q14393; -.
DR PRIDE; Q14393; -.
DR ProteomicsDB; 19251; -.
DR ProteomicsDB; 59975; -. [Q14393-1]
DR ProteomicsDB; 59976; -. [Q14393-2]
DR ProteomicsDB; 59977; -. [Q14393-3]
DR ProteomicsDB; 59978; -. [Q14393-4]
DR Antibodypedia; 1292; 405 antibodies from 33 providers.
DR DNASU; 2621; -.
DR Ensembl; ENST00000327773.7; ENSP00000331831.6; ENSG00000183087.15. [Q14393-2]
DR GeneID; 2621; -.
DR KEGG; hsa:2621; -.
DR MANE-Select; ENST00000327773.7; ENSP00000331831.6; NM_000820.4; NP_000811.1.
DR UCSC; uc001vud.4; human. [Q14393-2]
DR CTD; 2621; -.
DR DisGeNET; 2621; -.
DR GeneCards; GAS6; -.
DR HGNC; HGNC:4168; GAS6.
DR HPA; ENSG00000183087; Low tissue specificity.
DR MIM; 600441; gene.
DR neXtProt; NX_Q14393; -.
DR OpenTargets; ENSG00000183087; -.
DR PharmGKB; PA28582; -.
DR VEuPathDB; HostDB:ENSG00000183087; -.
DR eggNOG; ENOG502QT2N; Eukaryota.
DR GeneTree; ENSGT00940000161271; -.
DR HOGENOM; CLU_026236_0_0_1; -.
DR InParanoid; Q14393; -.
DR OMA; YTCHCNG; -.
DR OrthoDB; 317733at2759; -.
DR PhylomeDB; Q14393; -.
DR TreeFam; TF352157; -.
DR PathwayCommons; Q14393; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-159740; Gamma-carboxylation of protein precursors.
DR Reactome; R-HSA-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
DR Reactome; R-HSA-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins.
DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; Q14393; -.
DR SIGNOR; Q14393; -.
DR BioGRID-ORCS; 2621; 13 hits in 1081 CRISPR screens.
DR ChiTaRS; GAS6; human.
DR EvolutionaryTrace; Q14393; -.
DR GeneWiki; GAS6; -.
DR GenomeRNAi; 2621; -.
DR Pharos; Q14393; Tbio.
DR PRO; PR:Q14393; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q14393; protein.
DR Bgee; ENSG00000183087; Expressed in ascending aorta and 197 other tissues.
DR Genevisible; Q14393; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; IDA:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IDA:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISS:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0043277; P:apoptotic cell clearance; IDA:UniProtKB.
DR GO; GO:0035754; P:B cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IEA:Ensembl.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0031589; P:cell-substrate adhesion; IEA:Ensembl.
DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl.
DR GO; GO:0035457; P:cellular response to interferon-alpha; IDA:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
DR GO; GO:0071307; P:cellular response to vitamin K; IDA:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0097028; P:dendritic cell differentiation; IEP:UniProtKB.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; IEA:Ensembl.
DR GO; GO:0085029; P:extracellular matrix assembly; ISS:UniProtKB.
DR GO; GO:0044346; P:fibroblast apoptotic process; IEA:Ensembl.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IDA:UniProtKB.
DR GO; GO:0097241; P:hematopoietic stem cell migration to bone marrow; IDA:UniProtKB.
DR GO; GO:0033028; P:myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IDA:UniProtKB.
DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IDA:UniProtKB.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; IDA:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0033033; P:negative regulation of myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:1900142; P:negative regulation of oligodendrocyte apoptotic process; IDA:UniProtKB.
DR GO; GO:2000533; P:negative regulation of renal albumin absorption; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; IDA:UniProtKB.
DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0003104; P:positive regulation of glomerular filtration; ISS:UniProtKB.
DR GO; GO:0032825; P:positive regulation of natural killer cell differentiation; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IDA:UniProtKB.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IDA:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IDA:UniProtKB.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR GO; GO:0046718; P:viral entry into host cell; IDA:UniProtKB.
DR GO; GO:0019079; P:viral genome replication; IDA:UniProtKB.
DR CDD; cd00110; LamG; 2.
DR Gene3D; 4.10.740.10; -; 1.
DR InterPro; IPR026823; cEGF.
DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR013032; EGF-like_CS.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR035972; GLA-like_dom_SF.
DR InterPro; IPR000294; GLA_domain.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR001791; Laminin_G.
DR Pfam; PF12662; cEGF; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF00594; Gla; 1.
DR Pfam; PF12661; hEGF; 2.
DR Pfam; PF00054; Laminin_G_1; 1.
DR Pfam; PF02210; Laminin_G_2; 1.
DR PRINTS; PR00001; GLABLOOD.
DR SMART; SM00181; EGF; 4.
DR SMART; SM00179; EGF_CA; 4.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00282; LamG; 2.
DR SUPFAM; SSF49899; SSF49899; 2.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF57630; SSF57630; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 4.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS01186; EGF_2; 3.
DR PROSITE; PS50026; EGF_3; 4.
DR PROSITE; PS01187; EGF_CA; 3.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_2; 1.
DR PROSITE; PS50025; LAM_G_DOMAIN; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Disulfide bond;
KW EGF-like domain; Gamma-carboxyglutamic acid; Glycoprotein;
KW Growth regulation; Host-virus interaction; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..678
FT /note="Growth arrest-specific protein 6"
FT /id="PRO_0000007589"
FT DOMAIN 53..94
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 116..154
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 156..196
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 197..237
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 238..278
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 298..470
FT /note="Laminin G-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 477..670
FT /note="Laminin G-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT BINDING 329
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 331
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 440
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 656
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT MOD_RES 71
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:26091039"
FT MOD_RES 621
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63772"
FT MOD_RES 637
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q63772"
FT MOD_RES 640
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q63772"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16362042"
FT DISULFID 65..70
FT /evidence="ECO:0000250"
FT DISULFID 120..133
FT /evidence="ECO:0000250"
FT DISULFID 125..142
FT /evidence="ECO:0000250"
FT DISULFID 144..153
FT /evidence="ECO:0000250"
FT DISULFID 160..171
FT /evidence="ECO:0000250"
FT DISULFID 167..180
FT /evidence="ECO:0000250"
FT DISULFID 182..195
FT /evidence="ECO:0000250"
FT DISULFID 201..212
FT /evidence="ECO:0000250"
FT DISULFID 207..221
FT /evidence="ECO:0000250"
FT DISULFID 223..236
FT /evidence="ECO:0000250"
FT DISULFID 242..251
FT /evidence="ECO:0000250"
FT DISULFID 247..260
FT /evidence="ECO:0000250"
FT DISULFID 262..277
FT DISULFID 283..570
FT DISULFID 444..470
FT DISULFID 643..670
FT VAR_SEQ 1..299
FT /note="Missing (in isoform 5)"
FT /id="VSP_059767"
FT VAR_SEQ 1..273
FT /note="Missing (in isoform 4)"
FT /id="VSP_059768"
FT VAR_SEQ 1..94
FT /note="MAPSLSPGPAALRRAPQLLLLLLAAECALAALLPAREATQFLRPRQRRAFQV
FT FEEAKQGHLERECVEELCSREEAREVFENDPETDYFYPRYLD -> MCMCQASPPPAAL
FT AGCLLSSCVQPAREHGGAFSKAEWLSN (in isoform 3)"
FT /id="VSP_059769"
FT VAR_SEQ 278
FT /note="E -> ELEAGWPCPRHRRDGSPAARPGRGAQGSRSEGHIPDRRGPRPWQ
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9326368"
FT /id="VSP_059770"
FT VARIANT 41
FT /note="F -> L (in dbSNP:rs201378406)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038823"
FT VARIANT 231
FT /note="S -> Y (in dbSNP:rs146159446)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038824"
FT VARIANT 347
FT /note="V -> M (in dbSNP:rs144457857)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038825"
FT VARIANT 500
FT /note="G -> R (in dbSNP:rs7992146)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038826"
FT VARIANT 580
FT /note="S -> L (in dbSNP:rs79807310)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038827"
FT VARIANT 612
FT /note="E -> K (in dbSNP:rs73583241)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038828"
FT VARIANT 616
FT /note="R -> Q (in dbSNP:rs199700915)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_038829"
FT MUTAGEN 310
FT /note="R->E: Strongly reduced affinity for AXL. Abolishes
FT phosphorylation of AXL."
FT /evidence="ECO:0000269|PubMed:16362042"
FT MUTAGEN 312
FT /note="K->E: Strongly reduced affinity for AXL. Abolishes
FT phosphorylation of AXL."
FT /evidence="ECO:0000269|PubMed:16362042"
FT MUTAGEN 487
FT /note="F->A: Decreases activation of AXL."
FT /evidence="ECO:0000269|PubMed:8621659"
FT MUTAGEN 620
FT /note="L->A: Reduces affinity for AXL 15-fold and decreases
FT activation of AXL."
FT /evidence="ECO:0000269|PubMed:8621659"
FT MUTAGEN 660
FT /note="Y->A: Reduces affinity for AXL 3-fold."
FT /evidence="ECO:0000269|PubMed:8621659"
FT CONFLICT 356
FT /note="E -> K (in Ref. 3; BAG52469)"
FT /evidence="ECO:0000305"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:1H30"
FT TURN 272..275
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 276..279
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 320..327
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 330..339
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 343..351
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 354..361
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 364..373
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 380..386
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 388..395
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 398..404
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 409..413
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 420..425
FT /evidence="ECO:0007829|PDB:1H30"
FT HELIX 430..432
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 433..435
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 443..450
FT /evidence="ECO:0007829|PDB:1H30"
FT HELIX 457..463
FT /evidence="ECO:0007829|PDB:5VXZ"
FT HELIX 466..468
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 469..473
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 475..480
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 486..488
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 507..518
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 520..527
FT /evidence="ECO:0007829|PDB:1H30"
FT HELIX 528..530
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 532..541
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 545..547
FT /evidence="ECO:0007829|PDB:4RA0"
FT STRAND 552..557
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 560..566
FT /evidence="ECO:0007829|PDB:1H30"
FT HELIX 569..571
FT /evidence="ECO:0007829|PDB:5VXZ"
FT STRAND 575..582
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 585..590
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 596..599
FT /evidence="ECO:0007829|PDB:1H30"
FT HELIX 601..615
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 620..624
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 633..635
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 642..648
FT /evidence="ECO:0007829|PDB:1H30"
FT HELIX 655..657
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 658..661
FT /evidence="ECO:0007829|PDB:1H30"
FT STRAND 665..668
FT /evidence="ECO:0007829|PDB:5VXZ"
SQ SEQUENCE 678 AA; 74925 MW; BB6D8AB0F6C48EA9 CRC64;
MAPSLSPGPA ALRRAPQLLL LLLAAECALA ALLPAREATQ FLRPRQRRAF QVFEEAKQGH
LERECVEELC SREEAREVFE NDPETDYFYP RYLDCINKYG SPYTKNSGFA TCVQNLPDQC
TPNPCDRKGT QACQDLMGNF FCLCKAGWGG RLCDKDVNEC SQENGGCLQI CHNKPGSFHC
SCHSGFELSS DGRTCQDIDE CADSEACGEA RCKNLPGSYS CLCDEGFAYS SQEKACRDVD
ECLQGRCEQV CVNSPGSYTC HCDGRGGLKL SQDMDTCEDI LPCVPFSVAK SVKSLYLGRM
FSGTPVIRLR FKRLQPTRLV AEFDFRTFDP EGILLFAGGH QDSTWIVLAL RAGRLELQLR
YNGVGRVTSS GPVINHGMWQ TISVEELARN LVIKVNRDAV MKIAVAGDLF QPERGLYHLN
LTVGGIPFHE KDLVQPINPR LDGCMRSWNW LNGEDTTIQE TVKVNTRMQC FSVTERGSFY
PGSGFAFYSL DYMRTPLDVG TESTWEVEVV AHIRPAADTG VLFALWAPDL RAVPLSVALV
DYHSTKKLKK QLVVLAVEHT ALALMEIKVC DGQEHVVTVS LRDGEATLEV DGTRGQSEVS
AAQLQERLAV LERHLRSPVL TFAGGLPDVP VTSAPVTAFY RGCMTLEVNR RLLDLDEAAY
KHSDITAHSC PPVEPAAA
