P30530 (UFO_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase receptor UFO
EC=2.7.10.1

Alternative name(s):
AXL oncogene

Gene names

Name:	AXL
Synonyms:	UFO

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	894 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	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TENC1. Recruitment of GRB2 and phosphatidylinositol-3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. 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. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. In case of filovirus infection, seems to function as a cell entry factor. Ref.2 Ref.11 Ref.12 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.25
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Enzyme regulation	Activated by GAS6-binding and subsequent autophosphorylation. Ref.9 Ref.17
Subunit structure	Heterodimer and heterotetramer with ligand GAS6. Interacts with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and TENC1. Part a complex including AXL, TNK2 and GRB2, in which GRB2 promotes AXL recruitment by TNK2. Ref.8 Ref.9 Ref.10 Ref.13 Ref.16 Ref.23 Ref.26 Ref.28
Subcellular location	Cell membrane; Single-pass type I membrane protein Ref.7.
Tissue specificity	Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue. Ref.7
Post-translational modification	Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion. Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity. Ref.10 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.27
Involvement in disease	Note=AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thiroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloptoliferative disorders, prostatic carcinoma cells, or breast cancer.
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily. Contains 2 fibronectin type-III domains. Contains 2 Ig-like C2-type (immunoglobulin-like) domains. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Differentiation Immunity Innate immunity
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Oncogene Proto-oncogene
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	innate immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Long (identifier: P30530-1)

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 Short (identifier: P30530-2)

The sequence of this isoform differs from the canonical sequence as follows:
     429-437: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Potential

Chain

26 – 894

869

Tyrosine-protein kinase receptor UFO

PRO_0000024481

Regions

Topological domain

26 – 451

426

Extracellular Potential

Transmembrane

452 – 472

21

Helical; Potential

Topological domain

473 – 894

422

Cytoplasmic Potential

Domain

27 – 128

102

Ig-like C2-type 1

Domain

139 – 222

84

Ig-like C2-type 2

Domain

225 – 332

108

Fibronectin type-III 1

Domain

333 – 427

95

Fibronectin type-III 2

Domain

536 – 807

272

Protein kinase

Nucleotide binding

542 – 550

9

ATP By similarity

Region

26 – 92

67

Interaction with GAS6

Sites

Active site

672

1

Proton acceptor By similarity

Binding site

567

1

ATP By similarity

Amino acid modifications

Modified residue

100

1

Phosphoserine Ref.22

Modified residue

702

1

Phosphotyrosine Ref.20 Ref.27

Modified residue

703

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

779

1

Phosphotyrosine; by autocatalysis Ref.23

Modified residue

821

1

Phosphotyrosine; by autocatalysis Ref.23

Modified residue

866

1

Phosphotyrosine; by autocatalysis Ref.21 Ref.23

Modified residue

875

1

Phosphoserine Ref.24

Modified residue

884

1

Phosphoserine Ref.24

Glycosylation

43

1

N-linked (GlcNAc...) Potential

Glycosylation

157

1

N-linked (GlcNAc...) Potential

Glycosylation

198

1

N-linked (GlcNAc...) Potential

Glycosylation

339

1

N-linked (GlcNAc...) Potential

Glycosylation

345

1

N-linked (GlcNAc...) Potential

Glycosylation

401

1

N-linked (GlcNAc...) Potential

Disulfide bond

56 ↔ 117

By similarity

Disulfide bond

160 ↔ 205

By similarity

Natural variations

Alternative sequence

429 – 437

9

Missing in isoform Short.

VSP_005017

Natural variant

112

1

T → M. Ref.29
Corresponds to variant rs35202236 [ dbSNP | Ensembl ].

VAR_045596

Natural variant

266

1

N → D. Ref.1 Ref.2 Ref.3 Ref.5
Corresponds to variant rs7249222 [ dbSNP | Ensembl ].

VAR_057990

Natural variant

295

1

R → W in a lung neuroendocrine carcinoma sample; somatic mutation. Ref.29

VAR_045597

Natural variant

499

1

R → C in a gastric adenocarcinoma sample; somatic mutation. Ref.29

VAR_041877

Natural variant

515

1

S → G. Ref.29

VAR_041878

Experimental info

Mutagenesis

63

1

E → R: Slightly reduced affinity for GAS6. Ref.28

Mutagenesis

66

1

E → R: Reduced affinity for GAS6. Ref.28

Mutagenesis

84

1

T → R: Reduced affinity for GAS6. Ref.28

Sequence conflict

303

1

T → P in AAB20305. Ref.3

Sequence conflict

303

1

T → P in CAA40338. Ref.3

Sequence conflict

338

1

E → K in AAA61243. Ref.2

Sequence conflict

430

1

Q → E in AAB20305. Ref.3

Sequence conflict

430

1

Q → E in CAA40338. Ref.3

Sequence conflict

639

1

D → G in AAB20305. Ref.3

Sequence conflict

639

1

D → G in CAA40338. Ref.3

Sequence conflict

696

1

K → I Ref.7

Sequence conflict

764

1

Q → R in AAH32229. Ref.5

Secondary structure

1

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894

Helix Strand Turn

Details...

Beta strand

36 – 39

4

Beta strand

44 – 46

3

Beta strand

52 – 63

12

Beta strand

68 – 71

4

Beta strand

80 – 87

8

Beta strand

89 – 91

3

Beta strand

94 – 106

13

Beta strand

113 – 121

9

Beta strand

124 – 127

4

Beta strand

131 – 135

5

Beta strand

140 – 143

4

Beta strand

148 – 150

3

Beta strand

156 – 163

8

Beta strand

170 – 177

8

Beta strand

179 – 183

5

Beta strand

190 – 194

5

Beta strand

201 – 209

9

Beta strand

212 – 215

4

Beta strand

219 – 223

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified June 16, 2009. Version 3. Checksum: 2C2D3574EADA4116	FASTA	894	98,336
	10 20 30 40 50 60 MAWRCPRMGR VPLAWCLALC GWACMAPRGT QAEESPFVGN PGNITGARGL TGTLRCQLQV 70 80 90 100 110 120 QGEPPEVHWL RDGQILELAD STQTQVPLGE DEQDDWIVVS QLRITSLQLS DTGQYQCLVF 130 140 150 160 170 180 LGHQTFVSQP GYVGLEGLPY FLEEPEDRTV AANTPFNLSC QAQGPPEPVD LLWLQDAVPL 190 200 210 220 230 240 ATAPGHGPQR SLHVPGLNKT SSFSCEAHNA KGVTTSRTAT ITVLPQQPRN LHLVSRQPTE 250 260 270 280 290 300 LEVAWTPGLS GIYPLTHCTL QAVLSNDGMG IQAGEPDPPE EPLTSQASVP PHQLRLGSLH 310 320 330 340 350 360 PHTPYHIRVA CTSSQGPSSW THWLPVETPE GVPLGPPENI SATRNGSQAF VHWQEPRAPL 370 380 390 400 410 420 QGTLLGYRLA YQGQDTPEVL MDIGLRQEVT LELQGDGSVS NLTVCVAAYT AAGDGPWSLP 430 440 450 460 470 480 VPLEAWRPGQ AQPVHQLVKE PSTPAFSWPW WYVLLGAVVA AACVLILALF LVHRRKKETR 490 500 510 520 530 540 YGEVFEPTVE RGELVVRYRV RKSYSRRTTE ATLNSLGISE ELKEKLRDVM VDRHKVALGK 550 560 570 580 590 600 TLGEGEFGAV MEGQLNQDDS ILKVAVKTMK IAICTRSELE DFLSEAVCMK EFDHPNVMRL 610 620 630 640 650 660 IGVCFQGSER ESFPAPVVIL PFMKHGDLHS FLLYSRLGDQ PVYLPTQMLV KFMADIASGM 670 680 690 700 710 720 EYLSTKRFIH RDLAARNCML NENMSVCVAD FGLSKKIYNG DYYRQGRIAK MPVKWIAIES 730 740 750 760 770 780 LADRVYTSKS DVWSFGVTMW EIATRGQTPY PGVENSEIYD YLRQGNRLKQ PADCLDGLYA 790 800 810 820 830 840 LMSRCWELNP QDRPSFTELR EDLENTLKAL PPAQEPDEIL YVNMDEGGGY PEPPGAAGGA 850 860 870 880 890 DPPTQPDPKD SCSCLTAAEV HPAGRYVLCP STTPSPAQPA DRGSPAAPGQ EDGA
	Isoform Short [UniParc]. Checksum: AFF0212BA8EAEAA1	FASTA	885	97,377
	10 20 30 40 50 60 MAWRCPRMGR VPLAWCLALC GWACMAPRGT QAEESPFVGN PGNITGARGL TGTLRCQLQV 70 80 90 100 110 120 QGEPPEVHWL RDGQILELAD STQTQVPLGE DEQDDWIVVS QLRITSLQLS DTGQYQCLVF 130 140 150 160 170 180 LGHQTFVSQP GYVGLEGLPY FLEEPEDRTV AANTPFNLSC QAQGPPEPVD LLWLQDAVPL 190 200 210 220 230 240 ATAPGHGPQR SLHVPGLNKT SSFSCEAHNA KGVTTSRTAT ITVLPQQPRN LHLVSRQPTE 250 260 270 280 290 300 LEVAWTPGLS GIYPLTHCTL QAVLSNDGMG IQAGEPDPPE EPLTSQASVP PHQLRLGSLH 310 320 330 340 350 360 PHTPYHIRVA CTSSQGPSSW THWLPVETPE GVPLGPPENI SATRNGSQAF VHWQEPRAPL 370 380 390 400 410 420 QGTLLGYRLA YQGQDTPEVL MDIGLRQEVT LELQGDGSVS NLTVCVAAYT AAGDGPWSLP 430 440 450 460 470 480 VPLEAWRPVK EPSTPAFSWP WWYVLLGAVV AAACVLILAL FLVHRRKKET RYGEVFEPTV 490 500 510 520 530 540 ERGELVVRYR VRKSYSRRTT EATLNSLGIS EELKEKLRDV MVDRHKVALG KTLGEGEFGA 550 560 570 580 590 600 VMEGQLNQDD SILKVAVKTM KIAICTRSEL EDFLSEAVCM KEFDHPNVMR LIGVCFQGSE 610 620 630 640 650 660 RESFPAPVVI LPFMKHGDLH SFLLYSRLGD QPVYLPTQML VKFMADIASG MEYLSTKRFI 670 680 690 700 710 720 HRDLAARNCM LNENMSVCVA DFGLSKKIYN GDYYRQGRIA KMPVKWIAIE SLADRVYTSK 730 740 750 760 770 780 SDVWSFGVTM WEIATRGQTP YPGVENSEIY DYLRQGNRLK QPADCLDGLY ALMSRCWELN 790 800 810 820 830 840 PQDRPSFTEL REDLENTLKA LPPAQEPDEI LYVNMDEGGG YPEPPGAAGG ADPPTQPDPK 850 860 870 880 DSCSCLTAAE VHPAGRYVLC PSTTPSPAQP ADRGSPAAPG QEDGA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Putative tyrosine kinases expressed in K-562 human leukemia cells." Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K. Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990) [PubMed: 2247464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASP-266.
[2]	"AXL, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase." O'Bryan J.P., Frye R.A., Cogswell P.C., Neubauer A., Kitch B., Prokop C., Espinosa R., le Beau M.M., Earp H., Liu E.T. Mol. Cell. Biol. 11:5016-5031(1991) [PubMed: 1656220] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), VARIANT ASP-266, ROLE IN MYELOID LEUKEMIA. Tissue: Fibroblast.
[3]	"A novel putative tyrosine kinase receptor with oncogenic potential." Janssen J.W.G., Schulz A.S., Steenvoorden A.C.M., Schmidberger M., Strehl S., Ambros P., Bartram C.R. Oncogene 6:2113-2120(1991) [PubMed: 1834974] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), VARIANT ASP-266.
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), VARIANT ASP-266.
[6]	"A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes." Lee S.-T., Strunk K.M., Spritz R.A. Oncogene 8:3403-3410(1993) [PubMed: 8247543] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 674-730.
[7]	"Receptor tyrosine kinases expressed in metastatic colon cancer." Craven R.J., Xu L.H., Weiner T.M., Fridell Y.-W., Dent G.A., Srivastava S., Varnum B., Liu E.T., Cance W.G. Int. J. Cancer 60:791-797(1995) [PubMed: 7896447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 677-730, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Colon tumor.
[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: 7854420] [Abstract] Cited for: INTERACTION WITH LIGAND GAS6.
[9]	"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: 8621659] [Abstract] Cited for: INTERACTION WITH GAS6, ENZYME REGULATION.
[10]	"Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site." Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., Ullrich A., Bartram C.R., Janssen J.W. Oncogene 14:2619-2631(1997) [PubMed: 9178760] [Abstract] Cited for: PHOSPHORYLATION, INTERACTION WITH GRB2; LCK; PIK3R1; PIK3R2 AND PLCG1.
[11]	"A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145." Jacob A.N., Kalapurakal J., Davidson W.R., Kandpal G., Dunson N., Prashar Y., Kandpal R.P. Cancer Detect. Prev. 23:325-332(1999) [PubMed: 10403904] [Abstract] Cited for: ROLE IN PROSTATIC CARCINOMA.
[12]	"Estrogen dependent expression of the receptor tyrosine kinase axl in normal and malignant human breast." Berclaz G., Altermatt H.J., Rohrbach V., Kieffer I., Dreher E., Andres A.C. Ann. Oncol. 12:819-824(2001) [PubMed: 11484958] [Abstract] Cited for: ROLE IN BREAST CANCER.
[13]	"Interaction of Axl receptor tyrosine kinase with C1-TEN, a novel C1 domain-containing protein with homology to tensin." Hafizi S., Alindri F., Karlsson R., Dahlbaeck B. Biochem. Biophys. Res. Commun. 299:793-800(2002) [PubMed: 12470648] [Abstract] Cited for: INTERACTION WITH NCK2; PIK3R3; SOCS1 AND TENC1.
[14]	"Acidification prevents endothelial cell apoptosis by Axl activation." D'Arcangelo D., Gaetano C., Capogrossi M.C. Circ. Res. 91:E4-12(2002) [PubMed: 12364394] [Abstract] Cited for: FUNCTION OF THE GAS6/AXL SIGNALING PATHWAY.
[15]	"Expression of receptor-type tyrosine kinase, Axl, and its ligand, Gas6, in pediatric thyroid carcinomas around chernobyl." Ito M., Nakashima M., Nakayama T., Ohtsuru A., Nagayama Y., Takamura N., Demedchik E.P., Sekine I., Yamashita S. Thyroid 12:971-975(2002) [PubMed: 12490074] [Abstract] Cited for: ROLE IN THYROID CARCINOMAS.
[16]	"Effects of Gas6 and hydrogen peroxide in Axl ubiquitination and downregulation." Valverde P. Biochem. Biophys. Res. Commun. 333:180-185(2005) [PubMed: 15958209] [Abstract] Cited for: INTERACTION WITH CBL AND GAS6, UBIQUITINATION.
[17]	"Inhibition of vascular endothelial growth factor receptor 2-mediated endothelial cell activation by Axl tyrosine kinase receptor." Gallicchio M., Mitola S., Valdembri D., Fantozzi R., Varnum B., Avanzi G.C., Bussolino F. Blood 105:1970-1976(2005) [PubMed: 15507525] [Abstract] Cited for: ENZYME REGULATION, FUNCTION.
[18]	"Gas6 receptors Axl, Sky and Mer enhance platelet activation and regulate thrombotic responses." Gould W.R., Baxi S.M., Schroeder R., Peng Y.W., Leadley R.J., Peterson J.T., Perrin L.A. J. Thromb. Haemost. 3:733-741(2005) [PubMed: 15733062] [Abstract] Cited for: FUNCTION IN PLATELET ACTIVATION AND THROMBOTIC RESPONSE REGULATION.
[19]	"Tyro3 family-mediated cell entry of Ebola and Marburg viruses." Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T., Jones S., Feldmann H., Kawaoka Y. J. Virol. 80:10109-10116(2006) [PubMed: 17005688] [Abstract] Cited for: FUNCTION AS CELL ENTRY FACTOR IN FILOVIRUS INFECTION.
[20]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-702 AND TYR-703, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[21]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-866, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[22]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-100, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[23]	"In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in vitro mutagenesis defines the requisite binding sites for downstream Akt activation." Weinger J.G., Gohari P., Yan Y., Backer J.M., Varnum B., Shafit-Zagardo B. J. Neurochem. 106:134-146(2008) [PubMed: 18346204] [Abstract] Cited for: INTERACTION WITH GRB2; PIK3R1 AND PIK3R2, PHOSPHORYLATION AT TYR-779; TYR-821 AND TYR-866.
[24]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-875 AND SER-884, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"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: 18840707] [Abstract] Cited for: FUNCTION OF THE GAS6/AXL SIGNALING PATHWAY.
[26]	"Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling." Pao-Chun L., Chan P.M., Chan W., Manser E. J. Biol. Chem. 284:34954-34963(2009) [PubMed: 19815557] [Abstract] Cited for: INTERACTION WITH GRB2 AND TNK2.
[27]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-702, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[28]	"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: 16362042] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 33-227 IN COMPLEX WITH GAS6, MUTAGENESIS OF GLU-63; GLU-66 AND THR-84, SUBUNIT.
[29]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-112; TRP-295; CYS-499 AND GLY-515.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M76125 mRNA. Translation: AAA61243.1.
S65125 mRNA. Translation: AAB20305.1.
X57019 mRNA. Translation: CAA40338.1.
AC011510 Genomic DNA. No translation available.
BC032229 mRNA. Translation: AAH32229.1.

IPI

IPI00296992.
IPI00397361.

PIR

A41527.

RefSeq

NP_001690.2. NM_001699.4.
NP_068713.2. NM_021913.3.

UniGene

Hs.590970.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2C5D	X-ray	3.30	C/D	33-227	[»]

ProteinModelPortal

P30530.

SMR

P30530. Positions 8-427, 525-811.

ModBase

Search...

Protein-protein interaction databases

IntAct

P30530. 1 interaction.

MINT

MINT-2735752.

STRING

P30530.

PTM databases

PhosphoSite

P30530.

Polymorphism databases

DMDM

239938818.

Proteomic databases

PRIDE

P30530.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301178; ENSP00000301178; ENSG00000167601.

GeneID

558.

KEGG

hsa:558.

UCSC

uc010ehj.1. human.
uc010ehk.1. human.

Organism-specific databases

CTD

558.

GeneCards

GC19P041725.

HGNC

HGNC:905. AXL.

HPA

HPA037422.

MIM

109135. gene.

neXtProt

NX_P30530.

PharmGKB

PA25197.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12486.

HOGENOM

HBG444090.

HOVERGEN

HBG006346.

InParanoid

P30530.

OMA

GSLHPHT.

OrthoDB

EOG44BB1N.

PhylomeDB

P30530.

Enzyme and pathway databases

BRENDA

2.7.10.1. 2681.

Gene expression databases

ArrayExpress

P30530.

Bgee

P30530.

CleanEx

HS_AXL.

Genevestigator

P30530.

GermOnline

ENSG00000167601. Homo sapiens.

Family and domain databases

InterPro

IPR003961. Fibronectin_type3.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 4 hits.

KO

K05115.

Pfam

PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF07686. V-set. 1 hit.
[Graphical view]

PRINTS

PR00109. TYRKINASE.

SMART

SM00060. FN3. 2 hits.
SM00409. IG. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]

SUPFAM

SSF49265. FN_III-like. 2 hits.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS50853. FN3. 2 hits.
PS50835. IG_LIKE. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

SOURCE

Search...

Entry information

Entry name

UFO_HUMAN

Accession

Primary (citable) accession number: P30530
Secondary accession number(s): Q8N5L2, Q9UD27

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	June 16, 2009
Last modified:	January 25, 2012
This is version 133 of the entry and version 3 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.