UniProt Accession

 UFO_HUMAN; P30530; Q8N5L2; Q9UD27 

Genbank Protein ID

 M76125; S65125; X57019; AC011510; BC032229 

Genbank Nucleotide ID

 AAA61243.1; AAB20305.1; CAA40338.1; AAH32229.1 

Protein Name

 Tyrosine-protein kinase receptor UFO 

Protein Synonyms/Alias

 AXL oncogene 

Gene Name

 AXL 

Gene Synonyms/Alias

 UFO 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
523	LGISEELKEKLRDVM	ubiquitination	[1]
540	RHKVALGKTLGEGEF	ubiquitination	[1, 2, 3, 4, 5]
563	NQDDSILKVAVKTMK	ubiquitination	[1]
666	GMEYLSTKRFIHRDL	ubiquitination	[1, 3]
696	ADFGLSKKIYNGDYY	ubiquitination	[4]
714	RIAKMPVKWIAIESL	ubiquitination	[1, 3]
769	LRQGNRLKQPADCLD	ubiquitination	[3]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [3] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 27 128 Ig-like C2-type 1.
 DOMAIN 139 222 Ig-like C2-type 2.
 DOMAIN 225 332 Fibronectin type-III 1.
 DOMAIN 333 427 Fibronectin type-III 2.
 DOMAIN 536 807 Protein kinase.
 NP_BIND 542 550 ATP (By similarity).
 REGION 26 92 Interaction with GAS6.
 ACT_SITE 672 672 Proton acceptor (By similarity).
 BINDING 567 567 ATP (By similarity).
 MOD_RES 703 703 Phosphotyrosine; by autocatalysis (By
 MOD_RES 779 779 Phosphotyrosine; by autocatalysis.
 MOD_RES 821 821 Phosphotyrosine; by autocatalysis.
 MOD_RES 866 866 Phosphotyrosine; by autocatalysis.
 MOD_RES 884 884 Phosphoserine.
 CARBOHYD 43 43 N-linked (GlcNAc...) (Potential).
 CARBOHYD 157 157 N-linked (GlcNAc...) (Potential).
 CARBOHYD 198 198 N-linked (GlcNAc...) (Potential).
 CARBOHYD 339 339 N-linked (GlcNAc...) (Potential).
 CARBOHYD 345 345 N-linked (GlcNAc...) (Potential).
 CARBOHYD 401 401 N-linked (GlcNAc...) (Potential).
 DISULFID 56 117 By similarity.
 DISULFID 160 205 By similarity.  

Keyword

 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Complete proteome; Differentiation; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Innate immunity; Kinase; Membrane; Nucleotide-binding; Oncogene; Phosphoprotein; Polymorphism; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 894 AA 

Protein Sequence

Gene Ontology

 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0005615; C:extracellular space; IDA:UniProtKB.
 GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0001786; F:phosphatidylserine binding; IDA:UniProtKB.
 GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; TAS:ProtInc.
 GO:0043277; P:apoptotic cell clearance; IEA:Compara.
 GO:0001974; P:blood vessel remodeling; IEA:Compara.
 GO:0048469; P:cell maturation; IEP:UniProtKB.
 GO:0031668; P:cellular response to extracellular stimulus; IEA:Compara.
 GO:0035457; P:cellular response to interferon-alpha; IDA:UniProtKB.
 GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
 GO:0097028; P:dendritic cell differentiation; IEP:UniProtKB.
 GO:0007167; P:enzyme linked receptor protein signaling pathway; IEA:Compara.
 GO:0034101; P:erythrocyte homeostasis; IEA:Compara.
 GO:0021885; P:forebrain cell migration; IEA:Compara.
 GO:0006954; P:inflammatory response; IEA:Compara.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0001779; P:natural killer cell differentiation; IEA:Compara.
 GO:2000669; P:negative regulation of dendritic cell apoptotic process; IDA:UniProtKB.
 GO:0032689; P:negative regulation of interferon-gamma production; IDA:UniProtKB.
 GO:0051250; P:negative regulation of lymphocyte activation; IEA:Compara.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Compara.
 GO:0001764; P:neuron migration; IEA:Compara.
 GO:0042698; P:ovulation cycle; IEA:Compara.
 GO:0006909; P:phagocytosis; IDA:UniProtKB.
 GO:0030168; P:platelet activation; IEA:Compara.
 GO:0001961; P:positive regulation of cytokine-mediated signaling pathway; IDA:UniProtKB.
 GO:0032825; P:positive regulation of natural killer cell differentiation; IDA:UniProtKB.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Compara.
 GO:0043491; P:protein kinase B signaling cascade; IEA:Compara.
 GO:0032940; P:secretion by cell; IEA:Compara.
 GO:0007283; P:spermatogenesis; IEA:Compara.
 GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Compara.
 GO:0060068; P:vagina development; IEA:Compara. 

Interpro

 IPR003961; Fibronectin_type3.
 IPR007110; Ig-like_dom.
 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_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 

Pfam

 PF00041; fn3
 PF07714; Pkinase_Tyr
 PF07686; V-set 

SMART

 SM00060; FN3
 SM00409; IG
 SM00219; TyrKc 

PROSITE

 PS50853; FN3
 PS50835; IG_LIKE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR 

PRINTS

 PR00109; TYRKINASE.