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UniProtKB - Q14393 (GAS6_HUMAN)

Protein

Growth arrest-specific protein 6

Gene

GAS6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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.2 Publications
(Microbial infection) Can bridges virus envelope phosphatidylserine to the TAM receptor tyrosine kinase Axl to mediate viral entry by apoptotic mimicry (PubMed:21501828). Plays a role in Dengue cell entry by apoptotic mimicry (PubMed:23084921). Plays a role in Vaccinia virus cell entry by apoptotic mimicry (PubMed:21501828). Plays a role in ebolavirus and marburgvirus cell entry by apoptotic mimicry (PubMed:17005688).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi329Calcium1
Metal bindingi331Calcium; via carbonyl oxygen1
Metal bindingi440Calcium; via carbonyl oxygen1
Metal bindingi656Calcium1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Biological processGrowth regulation, Host-virus interaction
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-159740 Gamma-carboxylation of protein precursors
R-HSA-159763 Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-HSA-159782 Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-202733 Cell surface interactions at the vascular wall
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
SignaLinkiQ14393
SIGNORiQ14393

Names & Taxonomyi

Protein namesi
Recommended name:
Growth arrest-specific protein 6Curated
Short name:
GAS-6
Alternative name(s):
AXL receptor tyrosine kinase ligand
Gene namesi
Name:GAS6Imported
Synonyms:AXLLG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

EuPathDBiHostDB:ENSG00000183087.14
HGNCiHGNC:4168 GAS6
MIMi600441 gene
neXtProtiNX_Q14393

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi310R → E: Strongly reduced affinity for AXL. Abolishes phosphorylation of AXL. 1 Publication1
Mutagenesisi312K → E: Strongly reduced affinity for AXL. Abolishes phosphorylation of AXL. 1 Publication1
Mutagenesisi487F → A: Decreases activation of AXL. 1 Publication1
Mutagenesisi620L → A: Reduces affinity for AXL 15-fold and decreases activation of AXL. 1 Publication1
Mutagenesisi660Y → A: Reduces affinity for AXL 3-fold. 1 Publication1

Organism-specific databases

DisGeNETi2621
OpenTargetsiENSG00000183087
PharmGKBiPA28582

Polymorphism and mutation databases

BioMutaiGAS6
DMDMi48427995

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000000758931 – 678Growth arrest-specific protein 6Add BLAST648

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi65 ↔ 70By similarity
Modified residuei71Phosphoserine; by FAM20C1 Publication1
Disulfide bondi120 ↔ 133By similarity
Disulfide bondi125 ↔ 142By similarity
Disulfide bondi144 ↔ 153By similarity
Disulfide bondi160 ↔ 171By similarity
Disulfide bondi167 ↔ 180By similarity
Disulfide bondi182 ↔ 195By similarity
Disulfide bondi201 ↔ 212By similarity
Disulfide bondi207 ↔ 221By similarity
Disulfide bondi223 ↔ 236By similarity
Disulfide bondi242 ↔ 251By similarity
Disulfide bondi247 ↔ 260By similarity
Disulfide bondi262 ↔ 277
Disulfide bondi283 ↔ 570
Glycosylationi420N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi444 ↔ 470
Modified residuei621PhosphothreonineBy similarity1
Modified residuei637PhosphothreonineBy similarity1
Modified residuei640PhosphotyrosineBy similarity1
Disulfide bondi643 ↔ 670

Post-translational modificationi

Isoform 2: Proteolytically processed after secretion to yield a N-terminal 36 kDa protein and a C-terminal 50 kDa protein including the laminin G-like domains which activates AXL.1 Publication
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

EPDiQ14393
MaxQBiQ14393
PeptideAtlasiQ14393
PRIDEiQ14393
ProteomicsDBi59975
59976 [Q14393-2]
59977 [Q14393-3]
59978 [Q14393-4]

PTM databases

iPTMnetiQ14393
PhosphoSitePlusiQ14393

Expressioni

Tissue specificityi

Plasma. Isoform 1 and isoform 2 are widely expressed, isoform 1 being expressed at higher levels than isoform 2 in most tissues. Isoform 2 is the predominant form in spleen.2 Publications

Gene expression databases

BgeeiENSG00000183087 Expressed in 225 organ(s), highest expression level in thoracic aorta
CleanExiHS_GAS6
GenevisibleiQ14393 HS

Organism-specific databases

HPAiHPA008275
HPA056080

Interactioni

Subunit structurei

Heterodimer and heterotetramer with AXL.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
AXLP305308EBI-2802811,EBI-2850927

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108891, 33 interactors
IntActiQ14393, 13 interactors
MINTiQ14393

Structurei

Secondary structure

1678
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ14393
SMRiQ14393
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ14393

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini53 – 94GlaPROSITE-ProRule annotationAdd BLAST42
Domaini116 – 154EGF-like 1; calcium-bindingPROSITE-ProRule annotationAdd BLAST39
Domaini156 – 196EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST41
Domaini197 – 237EGF-like 3; calcium-bindingPROSITE-ProRule annotationAdd BLAST41
Domaini238 – 278EGF-like 4; calcium-bindingPROSITE-ProRule annotationAdd BLAST41
Domaini298 – 470Laminin G-like 1PROSITE-ProRule annotationAdd BLAST173
Domaini477 – 670Laminin G-like 2PROSITE-ProRule annotationAdd BLAST194

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

GeneTreeiENSGT00930000150853
HOGENOMiHOG000065758
HOVERGENiHBG051702
InParanoidiQ14393
KOiK05464
OMAiDEAAYKH
OrthoDBiEOG091G034Z
PhylomeDBiQ14393
TreeFamiTF352157

Family and domain databases

Gene3Di4.10.740.10, 1 hit
InterProiView protein in InterPro
IPR026823 cEGF
IPR017857 Coagulation_fac-like_Gla_dom
IPR013320 ConA-like_dom_sf
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR035972 GLA-like_dom_SF
IPR000294 GLA_domain
IPR009030 Growth_fac_rcpt_cys_sf
IPR001791 Laminin_G
PfamiView protein in Pfam
PF12662 cEGF, 1 hit
PF07645 EGF_CA, 1 hit
PF00594 Gla, 1 hit
PF12661 hEGF, 2 hits
PF00054 Laminin_G_1, 1 hit
PF02210 Laminin_G_2, 1 hit
PRINTSiPR00001 GLABLOOD
SMARTiView protein in SMART
SM00181 EGF, 4 hits
SM00179 EGF_CA, 4 hits
SM00069 GLA, 1 hit
SM00282 LamG, 2 hits
SUPFAMiSSF49899 SSF49899, 2 hits
SSF57184 SSF57184, 1 hit
SSF57630 SSF57630, 1 hit
PROSITEiView protein in PROSITE
PS00010 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

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q14393-2) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAPSLSPGPA ALRRAPQLLL LLLAAECALA ALLPAREATQ FLRPRQRRAF 
        60         70         80         90        100
QVFEEAKQGH LERECVEELC SREEAREVFE NDPETDYFYP RYLDCINKYG 
       110        120        130        140        150
SPYTKNSGFA TCVQNLPDQC TPNPCDRKGT QACQDLMGNF FCLCKAGWGG 
       160        170        180        190        200
RLCDKDVNEC SQENGGCLQI CHNKPGSFHC SCHSGFELSS DGRTCQDIDE 
       210        220        230        240        250
CADSEACGEA RCKNLPGSYS CLCDEGFAYS SQEKACRDVD ECLQGRCEQV 
       260        270        280        290        300
CVNSPGSYTC HCDGRGGLKL SQDMDTCEDI LPCVPFSVAK SVKSLYLGRM 
       310        320        330        340        350
FSGTPVIRLR FKRLQPTRLV AEFDFRTFDP EGILLFAGGH QDSTWIVLAL 
       360        370        380        390        400
RAGRLELQLR YNGVGRVTSS GPVINHGMWQ TISVEELARN LVIKVNRDAV 
       410        420        430        440        450
MKIAVAGDLF QPERGLYHLN LTVGGIPFHE KDLVQPINPR LDGCMRSWNW 
       460        470        480        490        500
LNGEDTTIQE TVKVNTRMQC FSVTERGSFY PGSGFAFYSL DYMRTPLDVG 
       510        520        530        540        550
TESTWEVEVV AHIRPAADTG VLFALWAPDL RAVPLSVALV DYHSTKKLKK 
       560        570        580        590        600
QLVVLAVEHT ALALMEIKVC DGQEHVVTVS LRDGEATLEV DGTRGQSEVS 
       610        620        630        640        650
AAQLQERLAV LERHLRSPVL TFAGGLPDVP VTSAPVTAFY RGCMTLEVNR 
       660        670 
RLLDLDEAAY KHSDITAHSC PPVEPAAA
Length:678
Mass (Da):74,925
Last modified:September 12, 2018 - v3
Checksum:iBB6D8AB0F6C48EA9
GO
Isoform 2 (identifier: Q14393-1) [UniParc]FASTAAdd to basket
Also known as: gas6SV1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     278-278: E → ELEAGWPCPRHRRDGSPAARPGRGAQGSRSEGHIPDRRGPRPWQ

Show »
Length:721
Mass (Da):79,677
Checksum:iE7B22B0E010930F9
GO
Isoform 3 (identifier: Q14393-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-94: MAPSLSPGPA...TDYFYPRYLD → MCMCQASPPP...AFSKAEWLSN

Note: No experimental confirmation available.
Show »
Length:624
Mass (Da):68,256
Checksum:i6CCEBDDE139C9F53
GO
Isoform 4 (identifier: Q14393-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-273: Missing.

Show »
Length:405
Mass (Da):44,841
Checksum:iECF30C620FA69B60
GO
Isoform 5 (identifier: Q14393-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-299: Missing.

Note: No experimental confirmation available.
Show »
Length:379
Mass (Da):41,986
Checksum:iA0EE62BA476927C6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti356E → K in BAG52469 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03882341F → L1 Publication1
Natural variantiVAR_038824231S → Y1 PublicationCorresponds to variant dbSNP:rs146159446Ensembl.1
Natural variantiVAR_038825347V → M1 Publication1
Natural variantiVAR_038826500G → R1 Publication1
Natural variantiVAR_038827580S → L1 Publication1
Natural variantiVAR_038828612E → K1 Publication1
Natural variantiVAR_038829616R → Q1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0597671 – 299Missing in isoform 5. Add BLAST299
Alternative sequenceiVSP_0597681 – 273Missing in isoform 4. Add BLAST273
Alternative sequenceiVSP_0597691 – 94MAPSL…PRYLD → MCMCQASPPPAALAGCLLSS CVQPAREHGGAFSKAEWLSN in isoform 3. Add BLAST94
Alternative sequenceiVSP_059770278E → ELEAGWPCPRHRRDGSPAAR PGRGAQGSRSEGHIPDRRGP RPWQ in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13720 mRNA Translation: AAA58494.1
AY256843
, AY256830, AY256831, AY256832, AY256833, AY256834, AY256835, AY256836, AY256837, AY256838, AY256839, AY256840, AY256841, AY256842 Genomic DNA Translation: AAO84057.1
AK092028 mRNA Translation: BAG52469.1
AK122969 mRNA Translation: BAG53826.1
AK126533 mRNA Translation: BAC86580.1
AK290803 mRNA Translation: BAF83492.1
EF631974 Genomic DNA Translation: ABR09277.1
BX072579 Genomic DNA No translation available.
BC038984 mRNA Translation: AAH38984.1
AY170372 Genomic DNA Translation: AAO41859.1
BK001240 Genomic DNA Translation: DAA01155.1
CCDSiCCDS45072.1 [Q14393-2]
PIRiB48089
RefSeqiNP_000811.1, NM_000820.3 [Q14393-2]
UniGeneiHs.646346

Genome annotation databases

EnsembliENST00000327773; ENSP00000331831; ENSG00000183087 [Q14393-2]
GeneIDi2621
KEGGihsa:2621
UCSCiuc001vud.4 human [Q14393-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13720 mRNA Translation: AAA58494.1
AY256843
, AY256830, AY256831, AY256832, AY256833, AY256834, AY256835, AY256836, AY256837, AY256838, AY256839, AY256840, AY256841, AY256842 Genomic DNA Translation: AAO84057.1
AK092028 mRNA Translation: BAG52469.1
AK122969 mRNA Translation: BAG53826.1
AK126533 mRNA Translation: BAC86580.1
AK290803 mRNA Translation: BAF83492.1
EF631974 Genomic DNA Translation: ABR09277.1
BX072579 Genomic DNA No translation available.
BC038984 mRNA Translation: AAH38984.1
AY170372 Genomic DNA Translation: AAO41859.1
BK001240 Genomic DNA Translation: DAA01155.1
CCDSiCCDS45072.1 [Q14393-2]
PIRiB48089
RefSeqiNP_000811.1, NM_000820.3 [Q14393-2]
UniGeneiHs.646346

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H30X-ray2.20A261-678[»]
2C5DX-ray3.30A/B261-678[»]
4RA0X-ray3.07A/B279-678[»]
5VXZX-ray2.30A/B281-675[»]
ProteinModelPortaliQ14393
SMRiQ14393
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108891, 33 interactors
IntActiQ14393, 13 interactors
MINTiQ14393

PTM databases

iPTMnetiQ14393
PhosphoSitePlusiQ14393

Polymorphism and mutation databases

BioMutaiGAS6
DMDMi48427995

Proteomic databases

EPDiQ14393
MaxQBiQ14393
PeptideAtlasiQ14393
PRIDEiQ14393
ProteomicsDBi59975
59976 [Q14393-2]
59977 [Q14393-3]
59978 [Q14393-4]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000327773; ENSP00000331831; ENSG00000183087 [Q14393-2]
GeneIDi2621
KEGGihsa:2621
UCSCiuc001vud.4 human [Q14393-2]

Organism-specific databases

CTDi2621
DisGeNETi2621
EuPathDBiHostDB:ENSG00000183087.14
GeneCardsiGAS6
HGNCiHGNC:4168 GAS6
HPAiHPA008275
HPA056080
MIMi600441 gene
neXtProtiNX_Q14393
OpenTargetsiENSG00000183087
PharmGKBiPA28582
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00930000150853
HOGENOMiHOG000065758
HOVERGENiHBG051702
InParanoidiQ14393
KOiK05464
OMAiDEAAYKH
OrthoDBiEOG091G034Z
PhylomeDBiQ14393
TreeFamiTF352157

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
R-HSA-159740 Gamma-carboxylation of protein precursors
R-HSA-159763 Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus
R-HSA-159782 Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-202733 Cell surface interactions at the vascular wall
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
SignaLinkiQ14393
SIGNORiQ14393

Miscellaneous databases

ChiTaRSiGAS6 human
EvolutionaryTraceiQ14393
GeneWikiiGAS6
GenomeRNAii2621
PROiPR:Q14393
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183087 Expressed in 225 organ(s), highest expression level in thoracic aorta
CleanExiHS_GAS6
GenevisibleiQ14393 HS

Family and domain databases

Gene3Di4.10.740.10, 1 hit
InterProiView protein in InterPro
IPR026823 cEGF
IPR017857 Coagulation_fac-like_Gla_dom
IPR013320 ConA-like_dom_sf
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR035972 GLA-like_dom_SF
IPR000294 GLA_domain
IPR009030 Growth_fac_rcpt_cys_sf
IPR001791 Laminin_G
PfamiView protein in Pfam
PF12662 cEGF, 1 hit
PF07645 EGF_CA, 1 hit
PF00594 Gla, 1 hit
PF12661 hEGF, 2 hits
PF00054 Laminin_G_1, 1 hit
PF02210 Laminin_G_2, 1 hit
PRINTSiPR00001 GLABLOOD
SMARTiView protein in SMART
SM00181 EGF, 4 hits
SM00179 EGF_CA, 4 hits
SM00069 GLA, 1 hit
SM00282 LamG, 2 hits
SUPFAMiSSF49899 SSF49899, 2 hits
SSF57184 SSF57184, 1 hit
SSF57630 SSF57630, 1 hit
PROSITEiView protein in PROSITE
PS00010 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
ProtoNetiSearch...

Entry informationi

Entry nameiGAS6_HUMAN
AccessioniPrimary (citable) accession number: Q14393
Secondary accession number(s): B3KRQ7
, B3KVL4, E9PBL7, Q6IMN1, Q7Z7N3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: September 12, 2018
Last modified: November 7, 2018
This is version 190 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
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