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 24-JAN-2024, entry version 223. 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 Q14393-2; P30530: AXL; NbExp=8; IntAct=EBI-21517417, 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 140. DR IntAct; Q14393; 34. DR MINT; Q14393; -. DR STRING; 9606.ENSP00000331831; -. DR BindingDB; Q14393; -. DR ChEMBL; CHEMBL4804247; -. DR GlyCosmos; Q14393; 1 site, No reported glycans. 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 PaxDb; 9606-ENSP00000331831; -. DR PeptideAtlas; 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 Pumba; Q14393; -. DR Antibodypedia; 1292; 463 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 AGR; HGNC:4168; -. 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; YHGVGRV; -. DR OrthoDB; 19806at2759; -. 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; 14 hits in 1160 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 199 other cell types or tissues. 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:0030674; F:protein-macromolecule adaptor activity; IDA:UniProtKB. DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProtKB. 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:0007166; P:cell surface receptor signaling pathway; 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:0045892; P:negative regulation of DNA-templated transcription; 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: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: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:0032689; P:negative regulation of type II interferon production; IDA:UniProtKB. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:0006909; P:phagocytosis; IDA:UniProtKB. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IBA:GO_Central. 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:0050766; P:positive regulation of phagocytosis; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS: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: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; cd00054; EGF_CA; 2. DR CDD; cd00110; LamG; 2. DR Gene3D; 2.60.120.200; -; 2. DR Gene3D; 4.10.740.10; Coagulation Factor IX; 1. DR Gene3D; 2.10.25.10; Laminin; 4. 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 PANTHER; PTHR24040:SF14; GROWTH ARREST-SPECIFIC PROTEIN 6; 1. DR PANTHER; PTHR24040; LAMININ G-LIKE DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF12662; cEGF; 1. DR Pfam; PF07645; EGF_CA; 1. DR Pfam; PF00594; Gla; 1. DR Pfam; PF12661; hEGF; 1. 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; Concanavalin A-like lectins/glucanases; 2. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF57630; GLA-domain; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 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. DR Genevisible; Q14393; HS. 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 //