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Protein

Growth arrest-specific protein 6

Gene

Gas6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Ligand for tyrosine-protein kinase receptors AXL, TYRO3 and MER whose signaling is implicated in cell growth and survival, cell adhesion and cell migration. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi326 – 3261CalciumBy similarity
Metal bindingi328 – 3281Calcium; via carbonyl oxygenBy similarity
Metal bindingi437 – 4371Calcium; via carbonyl oxygenBy similarity
Metal bindingi652 – 6521CalciumBy similarity

GO - Molecular functioni

  1. binding, bridging Source: UniProtKB
  2. calcium ion binding Source: InterPro
  3. cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
  4. phosphatidylserine binding Source: UniProtKB
  5. protein tyrosine kinase activator activity Source: UniProtKB
  6. receptor agonist activity Source: MGI
  7. receptor binding Source: UniProtKB
  8. receptor tyrosine kinase binding Source: MGI
  9. voltage-gated calcium channel activity Source: UniProtKB

GO - Biological processi

  1. activation of protein kinase B activity Source: UniProtKB
  2. apoptotic cell clearance Source: MGI
  3. B cell chemotaxis Source: UniProtKB
  4. blood coagulation Source: MGI
  5. calcium ion transmembrane transport Source: MGI
  6. cell-substrate adhesion Source: MGI
  7. cellular response to drug Source: UniProtKB
  8. cellular response to glucose stimulus Source: UniProtKB
  9. cellular response to growth factor stimulus Source: MGI
  10. cellular response to interferon-alpha Source: UniProtKB
  11. cellular response to starvation Source: MGI
  12. cellular response to vitamin K Source: UniProtKB
  13. dendritic cell differentiation Source: Ensembl
  14. enzyme linked receptor protein signaling pathway Source: MGI
  15. extracellular matrix assembly Source: UniProtKB
  16. fusion of virus membrane with host plasma membrane Source: UniProtKB
  17. hematopoietic stem cell migration to bone marrow Source: UniProtKB
  18. macrophage cytokine production Source: MGI
  19. negative regulation of apoptotic process Source: UniProtKB
  20. negative regulation of biomineral tissue development Source: UniProtKB
  21. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  22. negative regulation of dendritic cell apoptotic process Source: UniProtKB
  23. negative regulation of endothelial cell apoptotic process Source: UniProtKB
  24. negative regulation of fibroblast apoptotic process Source: UniProtKB
  25. negative regulation of interferon-gamma production Source: UniProtKB
  26. negative regulation of interleukin-1 secretion Source: UniProtKB
  27. negative regulation of interleukin-6 production Source: MGI
  28. negative regulation of interleukin-6 secretion Source: UniProtKB
  29. negative regulation of oligodendrocyte apoptotic process Source: MGI
  30. negative regulation of protein import into nucleus, translocation Source: UniProtKB
  31. negative regulation of renal albumin absorption Source: UniProtKB
  32. negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  33. negative regulation of transcription, DNA-templated Source: UniProtKB
  34. negative regulation of tumor necrosis factor-mediated signaling pathway Source: UniProtKB
  35. negative regulation of tumor necrosis factor production Source: UniProtKB
  36. neuron migration Source: MGI
  37. organ regeneration Source: Ensembl
  38. peptidyl-serine phosphorylation Source: UniProtKB
  39. phagocytosis Source: UniProtKB
  40. positive regulation of cytokine-mediated signaling pathway Source: UniProtKB
  41. positive regulation of dendritic cell chemotaxis Source: MGI
  42. positive regulation of ERK1 and ERK2 cascade Source: MGI
  43. positive regulation of fibroblast proliferation Source: UniProtKB
  44. positive regulation of gene expression Source: UniProtKB
  45. positive regulation of glomerular filtration Source: UniProtKB
  46. positive regulation of natural killer cell differentiation Source: UniProtKB
  47. positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
  48. positive regulation of phagocytosis Source: UniProtKB
  49. positive regulation of protein export from nucleus Source: UniProtKB
  50. positive regulation of protein kinase activity Source: UniProtKB
  51. positive regulation of protein kinase B signaling Source: UniProtKB
  52. positive regulation of protein phosphorylation Source: UniProtKB
  53. positive regulation of protein tyrosine kinase activity Source: UniProtKB
  54. positive regulation of TOR signaling Source: UniProtKB
  55. protein kinase B signaling Source: MGI
  56. protein phosphorylation Source: UniProtKB
  57. protein targeting to plasma membrane Source: UniProtKB
  58. receptor-mediated virion attachment to host cell Source: UniProtKB
  59. regulation of growth Source: UniProtKB-KW
  60. signal transduction Source: MGI
  61. viral entry into host cell Source: UniProtKB
  62. viral genome replication Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Growth regulation

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_278886. Cell surface interactions at the vascular wall.
REACT_281620. Gamma-carboxylation of protein precursors.
REACT_307071. Platelet degranulation.
REACT_351509. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
REACT_352087. Removal of aminoterminal propeptides from gamma-carboxylated proteins.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth arrest-specific protein 6
Short name:
GAS-6
Alternative name(s):
AXL receptor tyrosine kinase ligand
Gene namesi
Name:Gas6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:95660. Gas6.

Subcellular locationi

Secreted By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extracellular space Source: MGI
  3. extracellular vesicular exosome Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 674647Growth arrest-specific protein 6PRO_0000007590Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi62 ↔ 67By similarity
Disulfide bondi117 ↔ 130By similarity
Disulfide bondi122 ↔ 139By similarity
Disulfide bondi141 ↔ 150By similarity
Disulfide bondi157 ↔ 168By similarity
Disulfide bondi164 ↔ 177By similarity
Disulfide bondi179 ↔ 192By similarity
Disulfide bondi198 ↔ 209By similarity
Disulfide bondi204 ↔ 218By similarity
Disulfide bondi220 ↔ 233By similarity
Disulfide bondi239 ↔ 248By similarity
Disulfide bondi244 ↔ 257By similarity
Disulfide bondi259 ↔ 274By similarity
Disulfide bondi280 ↔ 566By similarity
Glycosylationi417 – 4171N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi441 ↔ 467By similarity
Glycosylationi488 – 4881N-linked (GlcNAc...)Sequence Analysis
Modified residuei609 – 6091PhosphothreonineBy similarity
Modified residuei614 – 6141PhosphoserineBy similarity
Modified residuei617 – 6171PhosphothreonineBy similarity
Modified residuei633 – 6331PhosphothreonineBy similarity
Modified residuei636 – 6361PhosphotyrosineBy similarity
Disulfide bondi639 ↔ 666By similarity

Post-translational modificationi

Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Gamma-carboxyglutamic acid, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ61592.
PaxDbiQ61592.
PRIDEiQ61592.

Expressioni

Gene expression databases

BgeeiQ61592.
CleanExiMM_GAS6.
GenevestigatoriQ61592.

Interactioni

Subunit structurei

Heterodimer and heterotetramer with AXL.

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000033828.

Structurei

3D structure databases

ProteinModelPortaliQ61592.
SMRiQ61592. Positions 50-672.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini50 – 9142GlaPROSITE-ProRule annotationAdd
BLAST
Domaini113 – 15139EGF-like 1; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini153 – 19341EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini194 – 23441EGF-like 3; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini235 – 27541EGF-like 4; calcium-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini295 – 467173Laminin G-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini474 – 666193Laminin G-like 2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 4 EGF-like domains.PROSITE-ProRule annotation
Contains 1 Gla (gamma-carboxy-glutamate) domain.PROSITE-ProRule annotation
Contains 2 laminin G-like domains.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiNOG149502.
GeneTreeiENSGT00530000063339.
HOGENOMiHOG000065758.
HOVERGENiHBG051702.
InParanoidiQ61592.
KOiK05464.
OMAiMEIKVCD.
OrthoDBiEOG7F5119.
PhylomeDBiQ61592.
TreeFamiTF352157.

Family and domain databases

Gene3Di2.60.120.200. 2 hits.
4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR013320. ConA-like_dom.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR009030. Growth_fac_rcpt_N_dom.
IPR001791. Laminin_G.
[Graphical view]
PfamiPF07645. EGF_CA. 1 hit.
PF00594. Gla. 1 hit.
PF02210. Laminin_G_2. 2 hits.
[Graphical view]
PRINTSiPR00001. GLABLOOD.
SMARTiSM00181. EGF. 1 hit.
SM00179. EGF_CA. 3 hits.
SM00069. GLA. 1 hit.
SM00282. LamG. 2 hits.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 2 hits.
SSF57184. SSF57184. 1 hit.
SSF57630. SSF57630. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 4 hits.
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 3 hits.
PS50026. EGF_3. 4 hits.
PS01187. EGF_CA. 3 hits.
PS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS50025. LAM_G_DOMAIN. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q61592-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPPPPGPAAA LGTALLLLLL ASESSHTVLL RAREAAQFLR PRQRRAYQVF
60 70 80 90 100
EEAKQGHLER ECVEEVCSKE EAREVFENDP ETEYFYPRYQ ECMRKYGRPE
110 120 130 140 150
EKNPDFAKCV QNLPDQCTPN PCDKKGTHIC QDLMGNFFCV CTDGWGGRLC
160 170 180 190 200
DKDVNECVQK NGGCSQVCHN KPGSFQCACH SGFSLASDGQ TCQDIDECTD
210 220 230 240 250
SDTCGDARCK NLPGSYSCLC DEGYTYSSKE KTCQDVDECQ QDRCEQTCVN
260 270 280 290 300
SPGSYTCHCD GRGGLKLSPD MDTCEDILPC VPFSMAKSVK SLYLGRMFSG
310 320 330 340 350
TPVIRLRFKR LQPTRLLAEF DFRTFDPEGV LFFAGGRSDS TWIVLGLRAG
360 370 380 390 400
RLELQLRYNG VGRITSSGPT INHGMWQTIS VEELERNLVI KVNKDAVMKI
410 420 430 440 450
AVAGELFQLE RGLYHLNLTV GGIPFKESEL VQPINPRLDG CMRSWNWLNG
460 470 480 490 500
EDSAIQETVK ANTKMQCFSV TERGSFFPGN GFATYRLNYT RTSLDVGTET
510 520 530 540 550
TWEVKVVARI RPATDTGVLL ALVGDDDVVP ISVALVDYHS TKKLKKQLVV
560 570 580 590 600
LAVEDVALAL MEIKVCDSQE HTVTVSLREG EATLEVDGTK GQSEVSTAQL
610 620 630 640 650
QERLDTLKTH LQGSVHTYVG GLPEVSVISA PVTAFYRGCM TLEVNGKILD
660 670
LDTASYKHSD ITSHSCPPVE HATP
Length:674
Mass (Da):74,610
Last modified:June 6, 2004 - v2
Checksum:i7C41F7693903F401
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti530 – 5301Missing in CAA42507 (PubMed:8336730).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59846 mRNA. Translation: CAA42507.1.
BC005444 mRNA. Translation: AAH05444.1.
CCDSiCCDS40232.1.
PIRiA48089.
RefSeqiNP_062394.2. NM_019521.2.
UniGeneiMm.3982.

Genome annotation databases

EnsembliENSMUST00000033828; ENSMUSP00000033828; ENSMUSG00000031451.
GeneIDi14456.
KEGGimmu:14456.
UCSCiuc009kya.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59846 mRNA. Translation: CAA42507.1.
BC005444 mRNA. Translation: AAH05444.1.
CCDSiCCDS40232.1.
PIRiA48089.
RefSeqiNP_062394.2. NM_019521.2.
UniGeneiMm.3982.

3D structure databases

ProteinModelPortaliQ61592.
SMRiQ61592. Positions 50-672.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000033828.

Proteomic databases

MaxQBiQ61592.
PaxDbiQ61592.
PRIDEiQ61592.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000033828; ENSMUSP00000033828; ENSMUSG00000031451.
GeneIDi14456.
KEGGimmu:14456.
UCSCiuc009kya.1. mouse.

Organism-specific databases

CTDi2621.
MGIiMGI:95660. Gas6.

Phylogenomic databases

eggNOGiNOG149502.
GeneTreeiENSGT00530000063339.
HOGENOMiHOG000065758.
HOVERGENiHBG051702.
InParanoidiQ61592.
KOiK05464.
OMAiMEIKVCD.
OrthoDBiEOG7F5119.
PhylomeDBiQ61592.
TreeFamiTF352157.

Enzyme and pathway databases

ReactomeiREACT_278886. Cell surface interactions at the vascular wall.
REACT_281620. Gamma-carboxylation of protein precursors.
REACT_307071. Platelet degranulation.
REACT_351509. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
REACT_352087. Removal of aminoterminal propeptides from gamma-carboxylated proteins.

Miscellaneous databases

ChiTaRSiGas6. mouse.
NextBioi286080.
PROiQ61592.
SOURCEiSearch...

Gene expression databases

BgeeiQ61592.
CleanExiMM_GAS6.
GenevestigatoriQ61592.

Family and domain databases

Gene3Di2.60.120.200. 2 hits.
4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR013320. ConA-like_dom.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR009030. Growth_fac_rcpt_N_dom.
IPR001791. Laminin_G.
[Graphical view]
PfamiPF07645. EGF_CA. 1 hit.
PF00594. Gla. 1 hit.
PF02210. Laminin_G_2. 2 hits.
[Graphical view]
PRINTSiPR00001. GLABLOOD.
SMARTiSM00181. EGF. 1 hit.
SM00179. EGF_CA. 3 hits.
SM00069. GLA. 1 hit.
SM00282. LamG. 2 hits.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 2 hits.
SSF57184. SSF57184. 1 hit.
SSF57630. SSF57630. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 4 hits.
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 3 hits.
PS50026. EGF_3. 4 hits.
PS01187. EGF_CA. 3 hits.
PS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS50025. LAM_G_DOMAIN. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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."
    Manfioletti G., Brancolini C., Avanzi G., Schneider C.
    Mol. Cell. Biol. 13:4976-4985(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis."
    Angelillo-Scherrer A., de Frutos P., Aparicio C., Melis E., Savi P., Lupu F., Arnout J., Dewerchin M., Hoylaerts M., Herbert J., Collen D., Dahlback B., Carmeliet P.
    Nat. Med. 7:215-221(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiGAS6_MOUSE
AccessioniPrimary (citable) accession number: Q61592
Secondary accession number(s): Q99K57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2004
Last sequence update: June 6, 2004
Last modified: March 31, 2015
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

GAS6 deficient mice show protection against thrombosis, but no spontaneous bleeding.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.