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Protein

Tyrosine-protein kinase receptor UFO

Gene

Axl

Organism
Mus musculus (Mouse)
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.2 Publications

Catalytic activityi

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

Enzyme regulationi

Activated by GAS6-binding and subsequent autophosphorylation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei561ATPPROSITE-ProRule annotation1
Active sitei666Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi536 – 544ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • animal organ regeneration Source: Ensembl
  • apoptotic cell clearance Source: MGI
  • blood vessel remodeling Source: MGI
  • cell maturation Source: Ensembl
  • cellular response to extracellular stimulus Source: MGI
  • cellular response to hydrogen peroxide Source: Ensembl
  • cellular response to interferon-alpha Source: MGI
  • cellular response to lipopolysaccharide Source: MGI
  • dendritic cell differentiation Source: Ensembl
  • enzyme linked receptor protein signaling pathway Source: MGI
  • erythrocyte homeostasis Source: MGI
  • forebrain cell migration Source: MGI
  • inflammatory response Source: MGI
  • innate immune response Source: UniProtKB-KW
  • natural killer cell differentiation Source: MGI
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cytokine production Source: MGI
  • negative regulation of dendritic cell apoptotic process Source: MGI
  • negative regulation of interferon-gamma production Source: MGI
  • negative regulation of lymphocyte activation Source: MGI
  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of tumor necrosis factor production Source: MGI
  • neuron migration Source: MGI
  • neutrophil clearance Source: MGI
  • ovulation cycle Source: MGI
  • phagocytosis Source: MGI
  • platelet activation Source: MGI
  • positive regulation of cytokine-mediated signaling pathway Source: MGI
  • positive regulation of natural killer cell differentiation Source: MGI
  • positive regulation of pinocytosis Source: MGI
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • protein kinase B signaling Source: MGI
  • secretion by cell Source: MGI
  • spermatogenesis Source: MGI
  • substrate adhesion-dependent cell spreading Source: MGI
  • vagina development Source: MGI
  • viral entry into host cell Source: MGI

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processDifferentiation, Immunity, Innate immunity
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 3474
ReactomeiR-MMU-4420097 VEGFA-VEGFR2 Pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase receptor UFO (EC:2.7.10.1)
Alternative name(s):
Adhesion-related kinase
Gene namesi
Name:Axl
Synonyms:Ark, Ufo
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1347244 Axl

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 domaini19 – 445ExtracellularSequence analysisAdd BLAST427
Transmembranei446 – 466HelicalSequence analysisAdd BLAST21
Topological domaini467 – 888CytoplasmicSequence analysisAdd BLAST422

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Keywords - Diseasei

Oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000002448219 – 888Tyrosine-protein kinase receptor UFOAdd BLAST870

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi37N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi50 ↔ 111PROSITE-ProRule annotation
Glycosylationi151N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi154 ↔ 199PROSITE-ProRule annotation
Glycosylationi192N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi333N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi339N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi395N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei697Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei773Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei815Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei860Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ00993
PaxDbiQ00993
PeptideAtlasiQ00993
PRIDEiQ00993

PTM databases

iPTMnetiQ00993
PhosphoSitePlusiQ00993

Miscellaneous databases

PMAP-CutDBQ80YQ3

Expressioni

Tissue specificityi

In distinct substructures of a broad spectrum of developing tissues (in the late embryogenesis). In cells forming organ capsules as well as in connective tissue structures (in adult).

Gene expression databases

BgeeiENSMUSG00000002602
CleanExiMM_AXL
ExpressionAtlasiQ00993 baseline and differential
GenevisibleiQ00993 MM

Interactioni

Subunit structurei

Heterodimer and heterotetramer with ligand GAS6 (By similarity). 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 (By similarity).By similarity

GO - Molecular functioni

  • protein heterodimerization activity Source: MGI

Protein-protein interaction databases

BioGridi204922, 5 interactors
IntActiQ00993, 2 interactors
MINTiQ00993
STRINGi10090.ENSMUSP00000002677

Structurei

3D structure databases

ProteinModelPortaliQ00993
SMRiQ00993
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 122Ig-like C2-type 1Add BLAST93
Domaini133 – 216Ig-like C2-type 2Add BLAST84
Domaini221 – 325Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST105
Domaini330 – 422Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST93
Domaini530 – 801Protein kinasePROSITE-ProRule annotationAdd BLAST272

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni19 – 86Interaction with GAS6By similarityAdd BLAST68

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
InParanoidiQ00993
KOiK05115
OMAiWKVVSQL
OrthoDBiEOG091G016X
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
PF13895 Ig_2, 1 hit
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

Sequencei

Sequence statusi: Complete.

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

Q00993-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRVPLAWWL ALCCWGCAAH KDTQTEAGSP FVGNPGNITG ARGLTGTLRC
60 70 80 90 100
ELQVQGEPPE VVWLRDGQIL ELADNTQTQV PLGEDWQDEW KVVSQLRISA
110 120 130 140 150
LQLSDAGEYQ CMVHLEGRTF VSQPGFVGLE GLPYFLEEPE DKAVPANTPF
160 170 180 190 200
NLSCQAQGPP EPVTLLWLQD AVPLAPVTGH SSQHSLQTPG LNKTSSFSCE
210 220 230 240 250
AHNAKGVTTS RTATITVLPQ RPHHLHVVSR QPTELEVAWT PGLSGIYPLT
260 270 280 290 300
HCNLQAVLSD DGVGIWLGKS DPPEDPLTLQ VSVPPHQLRL EKLLPHTPYH
310 320 330 340 350
IRISCSSSQG PSPWTHWLPV ETTEGVPLGP PENVSAMRNG SQVLVRWQEP
360 370 380 390 400
RVPLQGTLLG YRLAYRGQDT PEVLMDIGLT REVTLELRGD RPVANLTVSV
410 420 430 440 450
TAYTSAGDGP WSLPVPLEPW RPGQGQPLHH LVSEPPPRAF SWPWWYVLLG
460 470 480 490 500
ALVAAACVLI LALFLVHRRK KETRYGEVFE PTVERGELVV RYRVRKSYSR
510 520 530 540 550
RTTEATLNSL GISEELKEKL RDVMVDRHKV ALGKTLGEGE FGAVMEGQLN
560 570 580 590 600
QDDSILKVAV KTMKIAICTR SELEDFLSEA VCMKEFDHPN VMRLIGVCFQ
610 620 630 640 650
GSDREGFPEP VVILPFMKHG DLHSFLLYSR LGDQPVFLPT QMLVKFMADI
660 670 680 690 700
ASGMEYLSTK RFIHRDLAAR NCMLNENMSV CVADFGLSKK IYNGDYYRQG
710 720 730 740 750
RIAKMPVKWI AIESLADRVY TSKSDVWSFG VTMWEIATRG QTPYPGVENS
760 770 780 790 800
EIYDYLRQGN RLKQPVDCLD GLYALMSRCW ELNPRDRPSF AELREDLENT
810 820 830 840 850
LKALPPAQEP DEILYVNMDE GGSHLEPRGA AGGADPPTQP DPKDSCSCLT
860 870 880
AADVHSAGRY VLCPSTAPGP TLSADRGCPA PPGQEDGA
Length:888
Mass (Da):98,191
Last modified:July 27, 2011 - v2
Checksum:iC5350E3A8995E975
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti394A → R in CAA42158 (PubMed:1840679).Curated1
Sequence conflicti486G → P in CAA42158 (PubMed:1840679).Curated1
Sequence conflicti566A → V in CAA42158 (PubMed:1840679).Curated1
Sequence conflicti768C → F in CAA45097 (PubMed:1320243).Curated1
Sequence conflicti774A → S in CAA45097 (PubMed:1320243).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X63535 mRNA Translation: CAA45097.1
X59560 Genomic DNA Translation: CAA42158.1
AK155567 mRNA Translation: BAE33327.1
CH466593 Genomic DNA Translation: EDL24236.1
BC046618 mRNA Translation: AAH46618.1
BC050914 mRNA Translation: AAH50914.1
CCDSiCCDS20996.1
PIRiS23065
S23251
RefSeqiNP_033491.2, NM_009465.4
XP_006540052.1, XM_006539989.3
UniGeneiMm.4128

Genome annotation databases

EnsembliENSMUST00000002677; ENSMUSP00000002677; ENSMUSG00000002602
GeneIDi26362
KEGGimmu:26362
UCSCiuc009ftx.2 mouse

Similar proteinsi

Entry informationi

Entry nameiUFO_MOUSE
AccessioniPrimary (citable) accession number: Q00993
Secondary accession number(s): Q80YQ3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 175 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health