GAS6_RAT
ID GAS6_RAT Reviewed; 674 AA.
AC Q63772;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Growth arrest-specific protein 6;
DE Short=GAS-6;
DE AltName: Full=AXL receptor tyrosine kinase ligand;
DE AltName: Full=Growth-potentiating factor;
DE Short=GPF;
DE Flags: Precursor;
GN Name=Gas6;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7890695; DOI=10.1074/jbc.270.11.5702;
RA Nakano T., Higashino K., Kikuchi N., Kishino J., Nomura K., Fujita H.,
RA Ohara O., Arita H.;
RT "Vascular smooth muscle cell-derived, Gla-containing growth-potentiating
RT factor for Ca(2+)-mobilizing growth factors.";
RL J. Biol. Chem. 270:5702-5705(1995).
RN [2]
RP RECEPTOR INTERACTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=7559388; DOI=10.1074/jbc.270.39.22681;
RA Ohashi K., Nagata K., Toshima J., Nakano T., Arita H., Tsuda H., Suzuki K.,
RA Mizuno K.;
RT "Stimulation of sky receptor tyrosine kinase by the product of growth
RT arrest-specific gene 6.";
RL J. Biol. Chem. 270:22681-22684(1995).
RN [3]
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 [4]
RP GAMMA-CARBOXYGLUTAMATION.
RX PubMed=9163328; DOI=10.1042/bj3230387;
RA Nakano T., Kawamoto K., Kishino J., Nomura K., Higashino K., Arita H.;
RT "Requirement of gamma-carboxyglutamic acid residues for the biological
RT activity of Gas6: contribution of endogenous Gas6 to the proliferation of
RT vascular smooth muscle cells.";
RL Biochem. J. 323:387-392(1997).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-609; SER-614; THR-617;
RP THR-633 AND TYR-636, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer and heterotetramer with AXL.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7559388}.
CC -!- TISSUE SPECIFICITY: Plasma. {ECO:0000269|PubMed:7559388}.
CC -!- PTM: Gamma-carboxyglutamate residues are formed by vitamin K dependent
CC carboxylation. These residues are essential for the binding of calcium
CC (Probable). {ECO:0000305|PubMed:9163328}.
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DR EMBL; D42148; BAA07719.1; -; mRNA.
DR PIR; I55476; I55476.
DR AlphaFoldDB; Q63772; -.
DR SMR; Q63772; -.
DR STRING; 10116.ENSRNOP00000024677; -.
DR GlyGen; Q63772; 3 sites.
DR iPTMnet; Q63772; -.
DR PhosphoSitePlus; Q63772; -.
DR PaxDb; Q63772; -.
DR PRIDE; Q63772; -.
DR Ensembl; ENSRNOT00000024677; ENSRNOP00000024677; ENSRNOG00000018233.
DR UCSC; RGD:61913; rat.
DR RGD; 61913; Gas6.
DR eggNOG; ENOG502QT2N; Eukaryota.
DR GeneTree; ENSGT00940000161271; -.
DR HOGENOM; CLU_026236_0_0_1; -.
DR InParanoid; Q63772; -.
DR OMA; YTCHCNG; -.
DR PhylomeDB; Q63772; -.
DR TreeFam; TF352157; -.
DR Reactome; R-RNO-114608; Platelet degranulation.
DR Reactome; R-RNO-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
DR Reactome; R-RNO-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:Q63772; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000018233; Expressed in lung and 19 other tissues.
DR ExpressionAtlas; Q63772; baseline and differential.
DR Genevisible; Q63772; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0008083; F:growth factor activity; TAS:RGD.
DR GO; GO:0001786; F:phosphatidylserine binding; ISS:UniProtKB.
DR GO; GO:0030296; F:protein tyrosine kinase activator activity; ISS:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:UniProtKB.
DR GO; GO:0048018; F:receptor ligand activity; ISO:RGD.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISS:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; IDA:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB.
DR GO; GO:0035754; P:B cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; ISO:RGD.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:RGD.
DR GO; GO:0031589; P:cell-substrate adhesion; ISO:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:RGD.
DR GO; GO:0035457; P:cellular response to interferon-alpha; ISS:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
DR GO; GO:0071307; P:cellular response to vitamin K; ISS:UniProtKB.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0097028; P:dendritic cell differentiation; ISO:RGD.
DR GO; GO:0007167; P:enzyme-linked receptor protein signaling pathway; ISO:RGD.
DR GO; GO:0085029; P:extracellular matrix assembly; IEP:UniProtKB.
DR GO; GO:0044346; P:fibroblast apoptotic process; IEA:Ensembl.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; ISS:UniProtKB.
DR GO; GO:0097241; P:hematopoietic stem cell migration to bone marrow; ISS:UniProtKB.
DR GO; GO:0033028; P:myeloid cell apoptotic process; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0070168; P:negative regulation of biomineral tissue development; ISS:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; ISS:UniProtKB.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; ISS:UniProtKB.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS: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; ISS:UniProtKB.
DR GO; GO:2000533; P:negative regulation of renal albumin absorption; IEP:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:UniProtKB.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0006909; P:phagocytosis; ISS:UniProtKB.
DR GO; GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0003104; P:positive regulation of glomerular filtration; IDA:UniProtKB.
DR GO; GO:0032825; P:positive regulation of natural killer cell differentiation; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISS:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS: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; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IDA:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0046813; P:receptor-mediated virion attachment to host cell; ISS:UniProtKB.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR GO; GO:0042246; P:tissue regeneration; TAS:RGD.
DR GO; GO:0048771; P:tissue remodeling; TAS:RGD.
DR GO; GO:0046718; P:viral entry into host cell; ISS:UniProtKB.
DR GO; GO:0019079; P:viral genome replication; ISS:UniProtKB.
DR CDD; cd00110; LamG; 2.
DR Gene3D; 4.10.740.10; -; 1.
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; 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; PF07645; EGF_CA; 2.
DR Pfam; PF00594; Gla; 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; 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 Calcium; Disulfide bond; EGF-like domain; Gamma-carboxyglutamic acid;
KW Glycoprotein; Growth regulation; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..674
FT /note="Growth arrest-specific protein 6"
FT /id="PRO_0000007591"
FT DOMAIN 50..91
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 113..151
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 153..193
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 194..234
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 235..275
FT /note="EGF-like 4; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 295..467
FT /note="Laminin G-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT DOMAIN 474..666
FT /note="Laminin G-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00122"
FT BINDING 326
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 328
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 437
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 652
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14393"
FT MOD_RES 609
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 617
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 633
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 636
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT CARBOHYD 189
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 62..67
FT /evidence="ECO:0000250"
FT DISULFID 117..130
FT /evidence="ECO:0000250"
FT DISULFID 122..139
FT /evidence="ECO:0000250"
FT DISULFID 141..150
FT /evidence="ECO:0000250"
FT DISULFID 157..168
FT /evidence="ECO:0000250"
FT DISULFID 164..177
FT /evidence="ECO:0000250"
FT DISULFID 179..192
FT /evidence="ECO:0000250"
FT DISULFID 198..209
FT /evidence="ECO:0000250"
FT DISULFID 204..218
FT /evidence="ECO:0000250"
FT DISULFID 220..233
FT /evidence="ECO:0000250"
FT DISULFID 239..248
FT /evidence="ECO:0000250"
FT DISULFID 244..257
FT /evidence="ECO:0000250"
FT DISULFID 259..274
FT /evidence="ECO:0000250"
FT DISULFID 280..566
FT /evidence="ECO:0000250"
FT DISULFID 441..467
FT /evidence="ECO:0000250"
FT DISULFID 639..666
FT /evidence="ECO:0000250"
SQ SEQUENCE 674 AA; 74638 MW; FBF8F6B8664D6F2E CRC64;
MPPPPGPTAA LGTALLLLLL ASESSHTVLL RAREAAQFLR PRQRRAYQVF EEAKQGHLER
ECVEEVCSKE EAREVFENDP ETDYFYPRYQ ECMRKYGRPE DKNPNFATCV KNLPDQCTPN
PCDKKGTQLC QDLMGNFFCL CKDGWGGRLC DKDVNECSQK NGGCSQVCHN KPGSFQCACH
SGFSLQSDNK SCQDIDECTD SDTCGDARCK NLPGSYSCLC DKGYTYSSKE KTCQDVDECQ
QDRCEQTCVN SPGSYTCHCN GRGGLKLSPD MDTCEDILPC VPFSMAKSVK SLYLGRMFSG
TPVIRLRFKR LQPTRLLAEF DFRTFDPEGV LFFAGGRSDS TWIVLGLRAG RLELQLRYNG
VGRITSSGPT INHGMWQTIS VEELDRNLVI KVNKDAVMKI AVAGGLFQLE RGLYHLNLTV
GGIPFKESDL VQPINPRLDG CMRSWNWLNG EDSAIQETVK ANTKMQCFSV TERGSFFPGN
GFAFYSLNYT RTSLDVGTET TWEVEVVARI RPATDTGVLM ALVGDKDVVL LSVALVDYHS
TKKLKKQLVV LAVENVALAL MEIKVCDSQE HTVTVSLRDG EATLEVDGTK GQSEVSTAQL
QERLDLLKTR LQGSVLTFVG GLPDVQVTST PVTAFYRGCM TLEVNGKTLD LDTASYKHSD
ITSHSCPPVE HVTA
