Reviewed, UniProtKB/Swiss-Prot P30530 (UFO_HUMAN)

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	May function as a signal transducer between specific cell types of mesodermal origin. In case of filovirus infection, seems to function as a cell entry factor. Ref.8
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Subunit structure	Heterodimer and heterotetramer with GAS6. Ref.12
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.
Involvement in disease	Has transforming potential in patients with chronic myeloproliferative disorder or chronic myelocytic leukemia.
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
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Proto-oncogene
Domain	Immunoglobulin domain Repeat Signal Transmembrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro signal transduction Ref.2 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.2 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase activity Ref.2 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

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 SKP1 and 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

Modified residue

702

1

Phosphotyrosine

Modified residue

703

1

Phosphotyrosine; by autocatalysis By similarity

Modified residue

875

1

Phosphoserine

Modified residue

884

1

Phosphoserine

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

VAR_045596

Natural variant

266

1

N → D: dbSNP rs7249222.

VAR_057990

Natural variant

295

1

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

VAR_045597

Natural variant

499

1

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

VAR_041877

Natural variant

515

1

S → G

VAR_041878

Experimental info

Mutagenesis

63

1

E → R: Slightly reduced affinity for GAS6.

Mutagenesis

66

1

E → R: Reduced affinity for GAS6.

Mutagenesis

84

1

T → R: Reduced affinity for GAS6.

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. 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. 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]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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

EMBLGenBankDDBJ

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.

UniGene

Hs.590970

3D structure databases

PDBPDBe

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

ModBase

Search...

PTM databases

PhosphoSite

P30530.

Proteomic databases

PRIDE

P30530.

Genome annotation databases

Ensembl

ENSG00000167601. Homo sapiens. [Contig view]

Organism-specific databases

GeneCards

GC19P046416.

HGNC

HGNC:905. AXL.

MIM

109135. gene.

PharmGKB

PA25197.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P30530.

Enzyme and pathway databases

BRENDA

2.7.10.1. 247.

Gene expression databases

ArrayExpress

P30530.

Bgee

P30530.

CleanEx

HS_AXL.

GermOnline

ENSG00000167601. Homo sapiens.

Family and domain databases

InterPro

IPR015775. Axl_RTKs.
IPR008957. Fibronectin_typ-III-like_fold.
IPR003961. FN_III.
IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Tyr_pkinase.
IPR008266. Tyr_pkinase_AS.
[Graphical view]

Gene3D

G3DSA:2.60.40.30. FN_III-like. 1 hit.
G3DSA:2.60.40.10. Ig-like_fold. 2 hits.

PANTHER

PTHR23256:SF156. Axl_RTKs. 1 hit.

Pfam

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

PRINTS

PR00109. TYRKINASE.

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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

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 Resources

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:	June 16, 2009
This is version 103 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)