Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tyrosine-protein kinase receptor UFO

Gene

AXL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 TNS2. 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.8 Publications
(Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.4 Publications
(Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Activity regulationi

Activated by GAS6-binding and subsequent autophosphorylation.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei567ATPPROSITE-ProRule annotation1
Active sitei672Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi542 – 550ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHost cell receptor for virus entry, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processDifferentiation, Host-virus interaction, Immunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-4420097 VEGFA-VEGFR2 Pathway
SignaLinkiP30530
SIGNORiP30530

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase receptor UFO (EC:2.7.10.1)
Alternative name(s):
AXL oncogene
Gene namesi
Name:AXL
Synonyms:UFO
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000167601.11
HGNCiHGNC:905 AXL
MIMi109135 gene
neXtProtiNX_P30530

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 451ExtracellularSequence analysisAdd BLAST426
Transmembranei452 – 472HelicalSequence analysisAdd BLAST21
Topological domaini473 – 894CytoplasmicSequence analysisAdd BLAST422

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi63E → R: Slightly reduced affinity for GAS6. 1 Publication1
Mutagenesisi66E → R: Reduced affinity for GAS6. 1 Publication1
Mutagenesisi84T → R: Reduced affinity for GAS6. 1 Publication1

Keywords - Diseasei

Oncogene, Proto-oncogene

Organism-specific databases

DisGeNETi558
MalaCardsiAXL
OpenTargetsiENSG00000167601
PharmGKBiPA25197

Chemistry databases

ChEMBLiCHEMBL4895
GuidetoPHARMACOLOGYi1835

Polymorphism and mutation databases

BioMutaiAXL
DMDMi239938818

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000002448126 – 894Tyrosine-protein kinase receptor UFOAdd BLAST869

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi43N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi56 ↔ 117PROSITE-ProRule annotation
Glycosylationi157N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi160 ↔ 205PROSITE-ProRule annotation
Glycosylationi198N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi339N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi345N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi401N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei703Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei779Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei821Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei866Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei884PhosphoserineCombined sources1

Post-translational modificationi

Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion.1 Publication
Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP30530
MaxQBiP30530
PaxDbiP30530
PeptideAtlasiP30530
PRIDEiP30530
ProteomicsDBi54712
54713 [P30530-2]

PTM databases

iPTMnetiP30530
PhosphoSitePlusiP30530

Expressioni

Tissue specificityi

Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.1 Publication

Gene expression databases

BgeeiENSG00000167601 Expressed in 228 organ(s), highest expression level in synovial joint
CleanExiHS_AXL
ExpressionAtlasiP30530 baseline and differential
GenevisibleiP30530 HS

Organism-specific databases

HPAiCAB032501
HPA037422
HPA037423

Interactioni

Subunit structurei

Heterodimer and heterotetramer with ligand GAS6. Interacts with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and TNS2. Part of a complex including AXL, TNK2 and GRB2, in which GRB2 promotes AXL recruitment by TNK2.8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107036, 18 interactors
CORUMiP30530
IntActiP30530, 16 interactors
MINTiP30530
STRINGi9606.ENSP00000301178

Chemistry databases

BindingDBiP30530

Structurei

Secondary structure

1894
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP30530
SMRiP30530
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30530

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 128Ig-like C2-type 1Add BLAST102
Domaini139 – 222Ig-like C2-type 2Add BLAST84
Domaini227 – 331Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST105
Domaini336 – 428Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST93
Domaini536 – 807Protein kinasePROSITE-ProRule annotationAdd BLAST272

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni26 – 92Interaction with GAS6Add BLAST67

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IG6I Eukaryota
COG0515 LUCA
GeneTreeiENSGT00810000125384
HOGENOMiHOG000231685
HOVERGENiHBG006346
InParanoidiP30530
KOiK05115
OrthoDBiEOG091G016X
PhylomeDBiP30530
TreeFamiTF317402

Family and domain databases

CDDicd00063 FN3, 2 hits
Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF00041 fn3, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SM00409 IG, 2 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF49265 SSF49265, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.iShow all

Isoform Long (identifier: P30530-1) [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
MAWRCPRMGR VPLAWCLALC GWACMAPRGT QAEESPFVGN PGNITGARGL
60 70 80 90 100
TGTLRCQLQV QGEPPEVHWL RDGQILELAD STQTQVPLGE DEQDDWIVVS
110 120 130 140 150
QLRITSLQLS DTGQYQCLVF LGHQTFVSQP GYVGLEGLPY FLEEPEDRTV
160 170 180 190 200
AANTPFNLSC QAQGPPEPVD LLWLQDAVPL ATAPGHGPQR SLHVPGLNKT
210 220 230 240 250
SSFSCEAHNA KGVTTSRTAT ITVLPQQPRN LHLVSRQPTE LEVAWTPGLS
260 270 280 290 300
GIYPLTHCTL QAVLSDDGMG IQAGEPDPPE EPLTSQASVP PHQLRLGSLH
310 320 330 340 350
PHTPYHIRVA CTSSQGPSSW THWLPVETPE GVPLGPPENI SATRNGSQAF
360 370 380 390 400
VHWQEPRAPL QGTLLGYRLA YQGQDTPEVL MDIGLRQEVT LELQGDGSVS
410 420 430 440 450
NLTVCVAAYT AAGDGPWSLP VPLEAWRPGQ AQPVHQLVKE PSTPAFSWPW
460 470 480 490 500
WYVLLGAVVA AACVLILALF LVHRRKKETR YGEVFEPTVE RGELVVRYRV
510 520 530 540 550
RKSYSRRTTE ATLNSLGISE ELKEKLRDVM VDRHKVALGK TLGEGEFGAV
560 570 580 590 600
MEGQLNQDDS ILKVAVKTMK IAICTRSELE DFLSEAVCMK EFDHPNVMRL
610 620 630 640 650
IGVCFQGSER ESFPAPVVIL PFMKHGDLHS FLLYSRLGDQ PVYLPTQMLV
660 670 680 690 700
KFMADIASGM EYLSTKRFIH RDLAARNCML NENMSVCVAD FGLSKKIYNG
710 720 730 740 750
DYYRQGRIAK MPVKWIAIES LADRVYTSKS DVWSFGVTMW EIATRGQTPY
760 770 780 790 800
PGVENSEIYD YLRQGNRLKQ PADCLDGLYA LMSRCWELNP QDRPSFTELR
810 820 830 840 850
EDLENTLKAL PPAQEPDEIL YVNMDEGGGY PEPPGAAGGA DPPTQPDPKD
860 870 880 890
SCSCLTAAEV HPAGRYVLCP STTPSPAQPA DRGSPAAPGQ EDGA
Length:894
Mass (Da):98,337
Last modified:March 28, 2018 - v4
Checksum:i262D3659218E3202
GO
Isoform Short (identifier: P30530-2) [UniParc]FASTAAdd to basket

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

Show »
Length:885
Mass (Da):97,378
Checksum:i89293527B3D05B6E
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0R0W6M0R0W6_HUMAN
Tyrosine-protein kinase receptor UF...
AXL
626Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti303T → P in AAB20305 (PubMed:1834974).Curated1
Sequence conflicti303T → P in CAA40338 (PubMed:1834974).Curated1
Sequence conflicti338E → K in AAA61243 (PubMed:1656220).Curated1
Sequence conflicti430Q → E in AAB20305 (PubMed:1834974).Curated1
Sequence conflicti430Q → E in CAA40338 (PubMed:1834974).Curated1
Sequence conflicti639D → G in AAB20305 (PubMed:1834974).Curated1
Sequence conflicti639D → G in CAA40338 (PubMed:1834974).Curated1
Sequence conflicti696K → I no nucleotide entry (PubMed:7896447).Curated1
Sequence conflicti764Q → R in AAH32229 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_045596112T → M1 PublicationCorresponds to variant dbSNP:rs35202236Ensembl.1
Natural variantiVAR_057990266D → N. Corresponds to variant dbSNP:rs7249222Ensembl.1
Natural variantiVAR_045597295R → W in a lung neuroendocrine carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs751738506Ensembl.1
Natural variantiVAR_041877499R → C in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs747576071Ensembl.1
Natural variantiVAR_041878515S → G1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005017429 – 437Missing in isoform Short. 1 Publication9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS12574.1 [P30530-2]
CCDS12575.1 [P30530-1]
PIRiA41527
RefSeqiNP_001690.2, NM_001699.5 [P30530-2]
NP_068713.2, NM_021913.4 [P30530-1]
UniGeneiHs.590970

Genome annotation databases

EnsembliENST00000301178; ENSP00000301178; ENSG00000167601 [P30530-1]
ENST00000359092; ENSP00000351995; ENSG00000167601 [P30530-2]
GeneIDi558
KEGGihsa:558
UCSCiuc010ehj.5 human [P30530-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS12574.1 [P30530-2]
CCDS12575.1 [P30530-1]
PIRiA41527
RefSeqiNP_001690.2, NM_001699.5 [P30530-2]
NP_068713.2, NM_021913.4 [P30530-1]
UniGeneiHs.590970

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2C5DX-ray3.30C/D33-227[»]
4RA0X-ray3.07C/D33-227[»]
5U6BX-ray2.84A/B/C/D514-818[»]
5VXZX-ray2.30C/D34-135[»]
ProteinModelPortaliP30530
SMRiP30530
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107036, 18 interactors
CORUMiP30530
IntActiP30530, 16 interactors
MINTiP30530
STRINGi9606.ENSP00000301178

Chemistry databases

BindingDBiP30530
ChEMBLiCHEMBL4895
GuidetoPHARMACOLOGYi1835

PTM databases

iPTMnetiP30530
PhosphoSitePlusiP30530

Polymorphism and mutation databases

BioMutaiAXL
DMDMi239938818

Proteomic databases

EPDiP30530
MaxQBiP30530
PaxDbiP30530
PeptideAtlasiP30530
PRIDEiP30530
ProteomicsDBi54712
54713 [P30530-2]

Protocols and materials databases

DNASUi558
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301178; ENSP00000301178; ENSG00000167601 [P30530-1]
ENST00000359092; ENSP00000351995; ENSG00000167601 [P30530-2]
GeneIDi558
KEGGihsa:558
UCSCiuc010ehj.5 human [P30530-1]

Organism-specific databases

CTDi558
DisGeNETi558
EuPathDBiHostDB:ENSG00000167601.11
GeneCardsiAXL
HGNCiHGNC:905 AXL
HPAiCAB032501
HPA037422
HPA037423
MalaCardsiAXL
MIMi109135 gene
neXtProtiNX_P30530
OpenTargetsiENSG00000167601
PharmGKBiPA25197
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IG6I Eukaryota
COG0515 LUCA
GeneTreeiENSGT00810000125384
HOGENOMiHOG000231685
HOVERGENiHBG006346
InParanoidiP30530
KOiK05115
OrthoDBiEOG091G016X
PhylomeDBiP30530
TreeFamiTF317402

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-4420097 VEGFA-VEGFR2 Pathway
SignaLinkiP30530
SIGNORiP30530

Miscellaneous databases

ChiTaRSiAXL human
EvolutionaryTraceiP30530
GeneWikiiAXL_receptor_tyrosine_kinase
GenomeRNAii558
PROiPR:P30530
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167601 Expressed in 228 organ(s), highest expression level in synovial joint
CleanExiHS_AXL
ExpressionAtlasiP30530 baseline and differential
GenevisibleiP30530 HS

Family and domain databases

CDDicd00063 FN3, 2 hits
Gene3Di2.60.40.10, 4 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003599 Ig_sub
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF00041 fn3, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SM00409 IG, 2 hits
SM00219 TyrKc, 1 hit
SUPFAMiSSF48726 SSF48726, 2 hits
SSF49265 SSF49265, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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
ProtoNetiSearch...

Entry informationi

Entry nameiUFO_HUMAN
AccessioniPrimary (citable) accession number: P30530
Secondary accession number(s): Q8N5L2, Q9UD27
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: March 28, 2018
Last modified: September 12, 2018
This is version 199 of the entry and version 4 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again