Q14393 (GAS6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Growth arrest-specific protein 6
Short name=GAS-6

Alternative name(s):
AXL receptor tyrosine kinase ligand

Gene names

Name:	GAS6
Synonyms:	AXLLG

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	721 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.13 Ref.14
Subunit structure	Heterodimer and heterotetramer with AXL. Ref.16
Subcellular location	Secreted Ref.12.
Tissue specificity	Plasma. Isoform 1 and isoform 2 are widely expressed. Isoform 1 is the predominant form in spleen. Ref.1 Ref.10
Post-translational modification	Isoform 1 is 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. Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium By similarity.
Sequence similarities	Contains 4 EGF-like domains. Contains 1 Gla (gamma-carboxy-glutamate) domain. Contains 2 laminin G-like domains.

Ontologies

Keywords
Biological process	Growth regulation
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Repeat Signal
Ligand	Calcium Metal-binding
PTM	Disulfide bond Gamma-carboxyglutamic acid Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell chemotaxis Inferred from direct assay PubMed 19922767. Source: UniProtKB activation of protein kinase B activity Inferred from sequence or structural similarity. Source: UniProtKB apoptotic cell clearance Inferred from direct assay PubMed 21501828. Source: UniProtKB cell cycle arrest Traceable author statement PubMed 16564713. Source: UniProtKB cell proliferation Traceable author statement PubMed 16564713. Source: UniProtKB cell-substrate adhesion Inferred from electronic annotation. Source: Compara cellular response to drug Inferred from direct assay PubMed 16359517. Source: UniProtKB cellular response to glucose stimulus Inferred from sequence or structural similarity. Source: UniProtKB cellular response to growth factor stimulus Inferred from electronic annotation. Source: Compara cellular response to interferon-alpha Inferred from direct assay PubMed 19657094. Source: UniProtKB cellular response to starvation Inferred from electronic annotation. Source: Compara cellular response to vitamin K Inferred from direct assay PubMed 16359517. Source: UniProtKB dendritic cell differentiation Inferred from expression pattern PubMed 19657094. Source: UniProtKB enzyme linked receptor protein signaling pathway Inferred from electronic annotation. Source: Compara extracellular matrix assembly Inferred from sequence or structural similarity. Source: UniProtKB hematopoietic stem cell migration to bone marrow Inferred from direct assay PubMed 19922767. Source: UniProtKB macrophage cytokine production Inferred from electronic annotation. Source: Compara negative regulation of biomineral tissue development Inferred from direct assay PubMed 20048160. Source: UniProtKB negative regulation of dendritic cell apoptotic process Inferred from direct assay PubMed 19657094. Source: UniProtKB negative regulation of endothelial cell apoptotic process Inferred from direct assay PubMed 16359517PubMed 18680538PubMed 18760998. Source: UniProtKB negative regulation of fibroblast apoptotic process Inferred from direct assay PubMed 16359517. Source: UniProtKB negative regulation of interferon-gamma production Inferred from direct assay Ref.14. Source: UniProtKB negative regulation of interleukin-1 secretion Inferred from direct assay PubMed 20103767. Source: UniProtKB negative regulation of interleukin-6 production Inferred from direct assay PubMed 19657094. Source: UniProtKB negative regulation of interleukin-6 secretion Inferred from direct assay PubMed 20103767. Source: UniProtKB negative regulation of oligodendrocyte apoptotic process Inferred from direct assay PubMed 16723520. Source: UniProtKB negative regulation of protein import into nucleus, translocation Inferred from direct assay PubMed 20103767. Source: UniProtKB negative regulation of renal albumin absorption Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 18680538. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 18680538. Source: UniProtKB negative regulation of tumor necrosis factor production Inferred from direct assay PubMed 19657094PubMed 20103767. Source: UniProtKB negative regulation of tumor necrosis factor-mediated signaling pathway Inferred from direct assay PubMed 19657094. Source: UniProtKB neuron migration Inferred from electronic annotation. Source: Compara organ regeneration Inferred from electronic annotation. Source: Compara peptidyl-glutamic acid carboxylation Traceable author statement. Source: Reactome peptidyl-serine phosphorylation Inferred from direct assay PubMed 18680538PubMed 20103767. Source: UniProtKB platelet aggregation Traceable author statement PubMed 16564713. Source: UniProtKB platelet degranulation Traceable author statement. Source: Reactome positive regulation of ERK1 and ERK2 cascade Inferred from direct assay PubMed 15184064. Source: MGI positive regulation of TOR signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cytokine-mediated signaling pathway Inferred from mutant phenotype Ref.14. Source: UniProtKB positive regulation of dendritic cell chemotaxis Inferred from direct assay PubMed 19657094. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of gene expression Inferred from direct assay PubMed 19657094. Source: UniProtKB positive regulation of glomerular filtration Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of natural killer cell differentiation Inferred from direct assay Ref.14. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation Inferred from direct assay PubMed 16723520. Source: UniProtKB positive regulation of phagocytosis Inferred from direct assay PubMed 18395422. Source: UniProtKB positive regulation of protein export from nucleus Inferred from direct assay PubMed 18680538. Source: UniProtKB positive regulation of protein kinase B signaling cascade Inferred from direct assay PubMed 16359517PubMed 16723520PubMed 18680538. Source: UniProtKB post-translational protein modification Traceable author statement. Source: Reactome protein kinase B signaling cascade Inferred from direct assay PubMed 16723520PubMed 20103767. Source: UniProtKB protein targeting to plasma membrane Inferred from direct assay PubMed 16359517. Source: UniProtKB proteolysis Traceable author statement. Source: Reactome regulation of growth Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via membrane fusion with the plasma membrane Inferred from direct assay PubMed 21501828. Source: UniProtKB viral genome replication Inferred from direct assay PubMed 21501828. Source: UniProtKB virion attachment, binding of host cell surface receptor Inferred from direct assay PubMed 21501828. Source: UniProtKB
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome endoplasmic reticulum lumen Traceable author statement. Source: Reactome extracellular space Inferred from direct assay PubMed 18395422PubMed 19922767PubMed 20088931. Source: UniProtKB platelet alpha granule lumen Traceable author statement. Source: Reactome
Molecular_function	binding, bridging Inferred from direct assay PubMed 21501828. Source: UniProtKB calcium ion binding Inferred from electronic annotation. Source: InterPro cysteine-type endopeptidase inhibitor activity involved in apoptotic process Inferred from direct assay PubMed 16723520. Source: UniProtKB phosphatidylserine binding Inferred from direct assay PubMed 21501828. Source: UniProtKB protein tyrosine kinase activator activity Inferred from direct assay PubMed 20103767. Source: UniProtKB receptor agonist activity Inferred from direct assay PubMed 15184064. Source: MGI voltage-gated calcium channel activity Inferred from direct assay PubMed 18395422. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q14393-1)

Also known as: gas6SV;

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.

Isoform 2 (identifier: Q14393-2)

The sequence of this isoform differs from the canonical sequence as follows:
     279-321: Missing.

Isoform 3 (identifier: Q14393-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: Missing.
     55-94: EAKQGHLERE...TDYFYPRYLD → MCMCQASPPP...AFSKAEWLSN
     279-321: Missing.

Note: No experimental confirmation available.

Isoform 4 (identifier: Q14393-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-273: Missing.
     279-321: Missing.

Isoform 5 (identifier: Q14393-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-342: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Potential

Chain

31 – 721

691

Growth arrest-specific protein 6

PRO_0000007589

Regions

Domain

53 – 94

42

Gla

Domain

116 – 154

39

EGF-like 1; calcium-binding Potential

Domain

156 – 196

41

EGF-like 2; calcium-binding Potential

Domain

197 – 237

41

EGF-like 3; calcium-binding Potential

Domain

238 – 278

41

EGF-like 4; calcium-binding Potential

Domain

341 – 513

173

Laminin G-like 1

Domain

520 – 713

194

Laminin G-like 2

Sites

Metal binding

372

1

Calcium

Metal binding

374

1

Calcium; via carbonyl oxygen

Metal binding

483

1

Calcium; via carbonyl oxygen

Metal binding

699

1

Calcium

Amino acid modifications

Glycosylation

463

1

N-linked (GlcNAc...) Ref.16

Disulfide bond

65 ↔ 70

By similarity

Disulfide bond

120 ↔ 133

By similarity

Disulfide bond

125 ↔ 142

By similarity

Disulfide bond

144 ↔ 153

By similarity

Disulfide bond

160 ↔ 171

By similarity

Disulfide bond

167 ↔ 180

By similarity

Disulfide bond

182 ↔ 195

By similarity

Disulfide bond

201 ↔ 212

By similarity

Disulfide bond

207 ↔ 221

By similarity

Disulfide bond

223 ↔ 236

By similarity

Disulfide bond

242 ↔ 251

By similarity

Disulfide bond

247 ↔ 260

By similarity

Disulfide bond

262 ↔ 277

Disulfide bond

326 ↔ 613

Disulfide bond

487 ↔ 513

Disulfide bond

686 ↔ 713

Natural variations

Alternative sequence

1 – 342

342

Missing in isoform 5.

VSP_045685

Alternative sequence

1 – 273

273

Missing in isoform 4.

VSP_043832

Alternative sequence

1 – 54

54

Missing in isoform 3.

VSP_010492

Alternative sequence

55 – 94

40

EAKQG…PRYLD → MCMCQASPPPAALAGCLLSS CVQPAREHGGAFSKAEWLSN in isoform 3.

VSP_010493

Alternative sequence

279 – 321

43

Missing in isoform 2, isoform 3 and isoform 4.

VSP_010494

Natural variant

41

1

F → L. Ref.4

VAR_038823

Natural variant

231

1

S → Y. Ref.4

VAR_038824

Natural variant

390

1

V → M. Ref.4

VAR_038825

Natural variant

543

1

G → R. Ref.4

VAR_038826

Natural variant

623

1

S → L. Ref.4

VAR_038827

Natural variant

655

1

E → K. Ref.4

VAR_038828

Natural variant

659

1

R → Q. Ref.4

VAR_038829

Experimental info

Mutagenesis

353

1

R → E: Strongly reduced affinity for AXL. Abolishes phosphorylation of AXL. Ref.16

Mutagenesis

355

1

K → E: Strongly reduced affinity for AXL. Abolishes phosphorylation of AXL. Ref.16

Mutagenesis

530

1

F → A: Decreases activation of AXL. Ref.15

Mutagenesis

663

1

L → A: Reduces affinity for AXL 15-fold and decreases activation of AXL. Ref.15

Mutagenesis

703

1

Y → A: Reduces affinity for AXL 3-fold. Ref.15

Sequence conflict

399

1

E → K in BAG52469. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

721

Helix Strand Turn

Details...

Helix

264 – 266

3

Beta strand

268 – 271

4

Turn

272 – 275

4

Beta strand

276 – 278

3

Beta strand

337 – 339

3

Beta strand

350 – 353

4

Beta strand

356 – 358

3

Beta strand

363 – 370

8

Beta strand

373 – 382

10

Beta strand

386 – 394

9

Beta strand

397 – 404

8

Beta strand

407 – 416

10

Beta strand

419 – 421

3

Beta strand

423 – 429

7

Beta strand

431 – 438

8

Beta strand

441 – 447

7

Beta strand

452 – 456

5

Beta strand

459 – 461

3

Beta strand

463 – 468

6

Helix

473 – 475

3

Beta strand

476 – 478

3

Beta strand

486 – 493

8

Helix

501 – 507

7

Helix

509 – 511

3

Beta strand

512 – 516

5

Beta strand

518 – 523

6

Beta strand

529 – 531

3

Beta strand

550 – 561

12

Beta strand

563 – 570

8

Helix

571 – 573

3

Beta strand

575 – 584

10

Beta strand

595 – 600

6

Beta strand

603 – 609

7

Beta strand

618 – 625

8

Beta strand

628 – 633

6

Beta strand

639 – 642

4

Helix

644 – 658

15

Beta strand

663 – 667

5

Beta strand

676 – 678

3

Beta strand

685 – 691

7

Helix

698 – 700

3

Beta strand

701 – 704

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (gas6SV) [UniParc]. Last modified June 7, 2004. Version 2. Checksum: E7B22B0E010930F9	FASTA	721	79,677
	10 20 30 40 50 60 MAPSLSPGPA ALRRAPQLLL LLLAAECALA ALLPAREATQ FLRPRQRRAF QVFEEAKQGH 70 80 90 100 110 120 LERECVEELC SREEAREVFE NDPETDYFYP RYLDCINKYG SPYTKNSGFA TCVQNLPDQC 130 140 150 160 170 180 TPNPCDRKGT QACQDLMGNF FCLCKAGWGG RLCDKDVNEC SQENGGCLQI CHNKPGSFHC 190 200 210 220 230 240 SCHSGFELSS DGRTCQDIDE CADSEACGEA RCKNLPGSYS CLCDEGFAYS SQEKACRDVD 250 260 270 280 290 300 ECLQGRCEQV CVNSPGSYTC HCDGRGGLKL SQDMDTCELE AGWPCPRHRR DGSPAARPGR 310 320 330 340 350 360 GAQGSRSEGH IPDRRGPRPW QDILPCVPFS VAKSVKSLYL GRMFSGTPVI RLRFKRLQPT 370 380 390 400 410 420 RLVAEFDFRT FDPEGILLFA GGHQDSTWIV LALRAGRLEL QLRYNGVGRV TSSGPVINHG 430 440 450 460 470 480 MWQTISVEEL ARNLVIKVNR DAVMKIAVAG DLFQPERGLY HLNLTVGGIP FHEKDLVQPI 490 500 510 520 530 540 NPRLDGCMRS WNWLNGEDTT IQETVKVNTR MQCFSVTERG SFYPGSGFAF YSLDYMRTPL 550 560 570 580 590 600 DVGTESTWEV EVVAHIRPAA DTGVLFALWA PDLRAVPLSV ALVDYHSTKK LKKQLVVLAV 610 620 630 640 650 660 EHTALALMEI KVCDGQEHVV TVSLRDGEAT LEVDGTRGQS EVSAAQLQER LAVLERHLRS 670 680 690 700 710 720 PVLTFAGGLP DVPVTSAPVT AFYRGCMTLE VNRRLLDLDE AAYKHSDITA HSCPPVEPAA A
	Isoform 2 [UniParc]. Checksum: BB6D8AB0F6C48EA9	FASTA	678	74,925
	10 20 30 40 50 60 MAPSLSPGPA ALRRAPQLLL LLLAAECALA ALLPAREATQ FLRPRQRRAF QVFEEAKQGH 70 80 90 100 110 120 LERECVEELC SREEAREVFE NDPETDYFYP RYLDCINKYG SPYTKNSGFA TCVQNLPDQC 130 140 150 160 170 180 TPNPCDRKGT QACQDLMGNF FCLCKAGWGG RLCDKDVNEC SQENGGCLQI CHNKPGSFHC 190 200 210 220 230 240 SCHSGFELSS DGRTCQDIDE CADSEACGEA RCKNLPGSYS CLCDEGFAYS SQEKACRDVD 250 260 270 280 290 300 ECLQGRCEQV CVNSPGSYTC HCDGRGGLKL SQDMDTCEDI LPCVPFSVAK SVKSLYLGRM 310 320 330 340 350 360 FSGTPVIRLR FKRLQPTRLV AEFDFRTFDP EGILLFAGGH QDSTWIVLAL RAGRLELQLR 370 380 390 400 410 420 YNGVGRVTSS GPVINHGMWQ TISVEELARN LVIKVNRDAV MKIAVAGDLF QPERGLYHLN 430 440 450 460 470 480 LTVGGIPFHE KDLVQPINPR LDGCMRSWNW LNGEDTTIQE TVKVNTRMQC FSVTERGSFY 490 500 510 520 530 540 PGSGFAFYSL DYMRTPLDVG TESTWEVEVV AHIRPAADTG VLFALWAPDL RAVPLSVALV 550 560 570 580 590 600 DYHSTKKLKK QLVVLAVEHT ALALMEIKVC DGQEHVVTVS LRDGEATLEV DGTRGQSEVS 610 620 630 640 650 660 AAQLQERLAV LERHLRSPVL TFAGGLPDVP VTSAPVTAFY RGCMTLEVNR RLLDLDEAAY 670 KHSDITAHSC PPVEPAAA
	Isoform 3 [UniParc]. Checksum: 6CCEBDDE139C9F53	FASTA	624	68,256
	10 20 30 40 50 60 MCMCQASPPP AALAGCLLSS CVQPAREHGG AFSKAEWLSN CINKYGSPYT KNSGFATCVQ 70 80 90 100 110 120 NLPDQCTPNP CDRKGTQACQ DLMGNFFCLC KAGWGGRLCD KDVNECSQEN GGCLQICHNK 130 140 150 160 170 180 PGSFHCSCHS GFELSSDGRT CQDIDECADS EACGEARCKN LPGSYSCLCD EGFAYSSQEK 190 200 210 220 230 240 ACRDVDECLQ GRCEQVCVNS PGSYTCHCDG RGGLKLSQDM DTCEDILPCV PFSVAKSVKS 250 260 270 280 290 300 LYLGRMFSGT PVIRLRFKRL QPTRLVAEFD FRTFDPEGIL LFAGGHQDST WIVLALRAGR 310 320 330 340 350 360 LELQLRYNGV GRVTSSGPVI NHGMWQTISV EELARNLVIK VNRDAVMKIA VAGDLFQPER 370 380 390 400 410 420 GLYHLNLTVG GIPFHEKDLV QPINPRLDGC MRSWNWLNGE DTTIQETVKV NTRMQCFSVT 430 440 450 460 470 480 ERGSFYPGSG FAFYSLDYMR TPLDVGTEST WEVEVVAHIR PAADTGVLFA LWAPDLRAVP 490 500 510 520 530 540 LSVALVDYHS TKKLKKQLVV LAVEHTALAL MEIKVCDGQE HVVTVSLRDG EATLEVDGTR 550 560 570 580 590 600 GQSEVSAAQL QERLAVLERH LRSPVLTFAG GLPDVPVTSA PVTAFYRGCM TLEVNRRLLD 610 620 LDEAAYKHSD ITAHSCPPVE PAAA
	Isoform 4 [UniParc]. Checksum: ECF30C620FA69B60	FASTA	405	44,841
	10 20 30 40 50 60 MDTCEDILPC VPFSVAKSVK SLYLGRMFSG TPVIRLRFKR LQPTRLVAEF DFRTFDPEGI 70 80 90 100 110 120 LLFAGGHQDS TWIVLALRAG RLELQLRYNG VGRVTSSGPV INHGMWQTIS VEELARNLVI 130 140 150 160 170 180 KVNRDAVMKI AVAGDLFQPE RGLYHLNLTV GGIPFHEKDL VQPINPRLDG CMRSWNWLNG 190 200 210 220 230 240 EDTTIQETVK VNTRMQCFSV TERGSFYPGS GFAFYSLDYM RTPLDVGTES TWEVEVVAHI 250 260 270 280 290 300 RPAADTGVLF ALWAPDLRAV PLSVALVDYH STKKLKKQLV VLAVEHTALA LMEIKVCDGQ 310 320 330 340 350 360 EHVVTVSLRD GEATLEVDGT RGQSEVSAAQ LQERLAVLER HLRSPVLTFA GGLPDVPVTS 370 380 390 400 APVTAFYRGC MTLEVNRRLL DLDEAAYKHS DITAHSCPPV EPAAA
	Isoform 5 [UniParc]. Checksum: A0EE62BA476927C6	FASTA	379	41,986
	10 20 30 40 50 60 MFSGTPVIRL RFKRLQPTRL VAEFDFRTFD PEGILLFAGG HQDSTWIVLA LRAGRLELQL 70 80 90 100 110 120 RYNGVGRVTS SGPVINHGMW QTISVEELAR NLVIKVNRDA VMKIAVAGDL FQPERGLYHL 130 140 150 160 170 180 NLTVGGIPFH EKDLVQPINP RLDGCMRSWN WLNGEDTTIQ ETVKVNTRMQ CFSVTERGSF 190 200 210 220 230 240 YPGSGFAFYS LDYMRTPLDV GTESTWEVEV VAHIRPAADT GVLFALWAPD LRAVPLSVAL 250 260 270 280 290 300 VDYHSTKKLK KQLVVLAVEH TALALMEIKV CDGQEHVVTV SLRDGEATLE VDGTRGQSEV 310 320 330 340 350 360 SAAQLQERLA VLERHLRSPV LTFAGGLPDV PVTSAPVTAF YRGCMTLEVN RRLLDLDEAA 370 YKHSDITAHS CPPVEPAAA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY. Tissue: Cervix carcinoma.
[2]	"Human vitamin K-dependent GAS6: gene structure, allelic variation, and association with stroke." Munoz X., Sumoy L., Ramirez-Lorca R., Villar J., de Frutos P.G., Sala N. Hum. Mutat. 23:506-512(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3; 4 AND 5). Tissue: Kidney and Uterus.
[4]	SeattleSNPs variation discovery resource Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-41; TYR-231; MET-390; ARG-543; LEU-623; LYS-655 AND GLN-659.
[5]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Fetal lung and Fetal spleen.
[7]	Maree A.O., Hillmann A., McRedmond J.P., Fitzgerald D.J. Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-85.
[8]	"Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6." Varnum B.C., Young C., Elliott G., Garcia A., Bartley T.D., Fridell Y.W., Hunt R.W., Trail G., Clogston C., Toso R.J., Yanagihara D., Bennett L., Silber M., Merewether L.A., Tseng A., Escobar E., Liu E.T., Yamane H.K. Nature 373:623-626(1995) [PubMed] [Europe PMC] [Abstract] Cited for: RECEPTOR INTERACTION.
[9]	"The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases." Stitt T.N., Conn G., Gore M., Lai C., Bruno J., Radziejewski C., Mattsson K., Fisher J., Gies D.R., Jones P.F., Masiakowski P., Ryan T.E., Tobkes N.J., Chen D.H., DiStefano P.S., Long G.L., Basilico C., Goldfarb M.P. , Lemke G., Glass D.J., Yancopoulos G.D. Cell 80:661-670(1995) [PubMed] [Europe PMC] [Abstract] Cited for: RECEPTOR INTERACTION.
[10]	"Identification and tissue expression of a splice variant for the growth arrest-specific gene gas6." Marcandalli P., Gostissa M., Varnum B., Goruppi S., Schneider C. FEBS Lett. 415:56-58(1997) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 1), TISSUE SPECIFICITY.
[11]	"Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases." Nagata K., Ohashi K., Nakano T., Arita H., Zong C., Hanafusa H., Mizuno K. J. Biol. Chem. 271:30022-30027(1996) [PubMed] [Europe PMC] [Abstract] Cited for: RECEPTOR INTERACTION.
[12]	"The product of a gas6 splice variant allows the release of the domain responsible for Axl tyrosine kinase receptor activation." Goruppi S., Yamane H., Marcandalli P., Garcia A., Clogston C., Gostissa M., Varnum B., Schneider C. FEBS Lett. 415:59-63(1997) [PubMed] [Europe PMC] [Abstract] Cited for: RECEPTOR INTERACTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[13]	"Acidification prevents endothelial cell apoptosis by Axl activation." D'Arcangelo D., Gaetano C., Capogrossi M.C. Circ. Res. 91:E4-12(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE GAS6/AXL SIGNALING PATHWAY.
[14]	"The Axl/Gas6 pathway is required for optimal cytokine signaling during human natural killer cell development." Park I.K., Giovenzana C., Hughes T.L., Yu J., Trotta R., Caligiuri M.A. Blood 113:2470-2477(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION OF THE GAS6/AXL SIGNALING PATHWAY.
[15]	"Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl." Mark M.R., Chen J., Hammonds R.G., Sadick M., Godowski P.J. J. Biol. Chem. 271:9785-9789(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 261-721 (ISOFORM 2), MUTAGENESIS OF PHE-530; LEU-663 AND TYR-703, INTERACTION WITH AXL.
[16]	"Structural basis for Gas6-Axl signalling." Sasaki T., Knyazev P.G., Clout N.J., Cheburkin Y., Goehring W., Ullrich A., Timpl R., Hohenester E. EMBO J. 25:80-87(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 322-721 IN COMPLEX WITH AXL, SUBUNIT, GLYCOSYLATION AT ASN-463, MUTAGENESIS OF ARG-353 AND LYS-355.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. Translation: CAH71174.1.
BC038984 mRNA. Translation: AAH38984.1.
AY170372 Genomic DNA. Translation: AAO41859.1.
BK001240 Genomic DNA. Translation: DAA01155.1.

IPI

IPI00032532.
IPI00412410.
IPI00412412.
IPI00921021.

PIR

B48089.

RefSeq

NP_000811.1. NM_000820.2.
NP_001137417.1. NM_001143945.1.
NP_001137418.1. NM_001143946.1.

UniGene

Hs.646346.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H30	X-ray	2.20	A	261-721	[»]
2C5D	X-ray	3.30	A/B	261-721	[»]

ProteinModelPortal

Q14393.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14393. 2 interactions.

MINT

MINT-2735698.

STRING

9606.ENSP00000331831.

PTM databases

PhosphoSite

Q14393.

Polymorphism databases

DMDM

48427995.

Proteomic databases

PaxDb

Q14393.

PRIDE

Q14393.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000327773; ENSP00000331831; ENSG00000183087.
ENST00000355761; ENSP00000348003; ENSG00000183087.
ENST00000418959; ENSP00000400117; ENSG00000183087.
ENST00000450766; ENSP00000416498; ENSG00000183087.

GeneID

2621.

KEGG

hsa:2621.

UCSC

uc001vud.3. human.
uc001vug.3. human.

Organism-specific databases

CTD

2621.

GeneCards

GC13M114523.

HGNC

HGNC:4168. GAS6.

HPA

HPA008275.

MIM

600441. gene.

neXtProt

NX_Q14393.

PharmGKB

PA28582.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG149502.

HOGENOM

HOG000065758.

HOVERGEN

HBG051702.

InParanoid

Q14393.

KO

K05464.

Enzyme and pathway databases

Reactome

REACT_17015. Metabolism of proteins.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

Q14393.

Bgee

Q14393.

CleanEx

HS_GAS6.

Genevestigator

Q14393.

GermOnline

ENSG00000183087. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.200. 2 hits.
4.10.740.10. 1 hit.

InterPro

IPR026823. cEGF.
IPR017857. Coagulation_fac_subgr_Gla_dom.
IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR001791. Laminin_G.
[Graphical view]

Pfam

PF12662. cEGF. 1 hit.
PF07645. EGF_CA. 1 hit.
PF00594. Gla. 1 hit.
PF00054. Laminin_G_1. 1 hit.
PF02210. Laminin_G_2. 1 hit.
[Graphical view]

PRINTS

PR00001. GLABLOOD.

SMART

SM00181. EGF. 1 hit.
SM00179. EGF_CA. 3 hits.
SM00069. GLA. 1 hit.
SM00282. LamG. 2 hits.
[Graphical view]

SUPFAM

SSF49899. ConA_like_lec_gl. 2 hits.
SSF57630. VitK_dep_GLA. 1 hit.

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.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

GAS6. human.

EvolutionaryTrace

Q14393.

GenomeRNAi

2621.

NextBio

10323.

SOURCE

Search...

Entry information

Entry name

GAS6_HUMAN

Accession

Primary (citable) accession number: Q14393
Secondary accession number(s): B3KRQ7 , B3KVL4, E9PBL7, Q6IMN1, Q7Z7N3

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	June 7, 2004
Last modified:	May 1, 2013
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.