UFO_HUMAN » Tyrosine-protein kinase receptor UFO

UFO_HUMAN » Tyrosine-protein kinase receptor UFO
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
UFO_HUMAN » Tyrosine-protein kinase receptor UFO » AXL oncogene;
Hydrophobic Thickness 33.6 ± 2.2 Å
Tilt Angle 0 ± 2°
ΔGtransfer -52.1 kcal/mol
ΔGfold -24.7 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 448-473 (447-478)
Pathways none
PDB 2c5d (C/D=33-227), 4ra0 (C/D=33-227)
OPM none
Complexes none
Interactions

ADA10, Complex: ADA10:UFO, PubMed

I15RA, Complex: UFO:I15RA, PubMed

IL2RG, Complex: IL2RG:UFO, PubMed

MERTK, Complex: UFO:MERTK, PubMed

TYRO3, Complex: TYRO3:UFO

Domains

AA: 37-120, PDBID: 2C5D, Subunit D, Seq Identity:100%, Immunoglobulin domain

AA: 226-321, PDBID: 1X5Z, Subunit A, Seq Identity:24%, Fibronectin type III domain

AA: 335-418, PDBID: 1QG3, Subunit A, Seq Identity:28%, Fibronectin type III domain

AA: 536-803, PDBID: 2P0C, Subunit A, Seq Identity:62%, Protein tyrosine kinase

UniProt annotation for UFO_HUMAN » Tyrosine-protein kinase receptor UFO
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 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. In case of filovirus infection, seems to function as a cell entry factor.

CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

ENZYME REGULATION: Activated by GAS6-binding and subsequent autophosphorylation.

SUBUNIT: 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.

TISSUE SPECIFICITY: Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.

DISEASE: Note=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.

UniProt features for UFO_HUMAN » Tyrosine-protein kinase receptor UFO
SIGNAL 1 25 Potential.
CHAIN 26 894 Tyrosine-protein kinase receptor UFO.
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.
REGION 26 92 Interaction with GAS6.
ACT_SITE 672 672 Proton acceptor (By similarity).
DISULFID 56 117 By similarity.
DISULFID 160 205 By similarity.
Amino Acid Sequence for UFO_HUMAN » Tyrosine-protein kinase receptor UFO
MAWRCPRMGR VPLAWCLALC GWACMAPRGT QAEESPFVGN PGNITGARGL TGTLRCQLQV QGEPPEVHWL RDGQILELAD STQTQVPLGE DEQDDWIVVS QLRITSLQLS DTGQYQCLVF LGHQTFVSQP GYVGLEGLPY FLEEPEDRTV AANTPFNLSC QAQGPPEPVD LLWLQDAVPL ATAPGHGPQR SLHVPGLNKT SSFSCEAHNA KGVTTSRTAT ITVLPQQPRN LHLVSRQPTE LEVAWTPGLS GIYPLTHCTL QAVLSNDGMG IQAGEPDPPE EPLTSQASVP PHQLRLGSLH PHTPYHIRVA CTSSQGPSSW THWLPVETPE GVPLGPPENI SATRNGSQAF VHWQEPRAPL QGTLLGYRLA YQGQDTPEVL MDIGLRQEVT LELQGDGSVS NLTVCVAAYT AAGDGPWSLP VPLEAWRPGQ AQPVHQLVKE PSTPAFSWPW WYVLLGAVVA AACVLILALF LVHRRKKETR YGEVFEPTVE RGELVVRYRV RKSYSRRTTE ATLNSLGISE ELKEKLRDVM VDRHKVALGK TLGEGEFGAV MEGQLNQDDS ILKVAVKTMK IAICTRSELE DFLSEAVCMK EFDHPNVMRL IGVCFQGSER ESFPAPVVIL PFMKHGDLHS FLLYSRLGDQ PVYLPTQMLV KFMADIASGM EYLSTKRFIH RDLAARNCML NENMSVCVAD FGLSKKIYNG DYYRQGRIAK MPVKWIAIES LADRVYTSKS DVWSFGVTMW EIATRGQTPY PGVENSEIYD YLRQGNRLKQ PADCLDGLYA LMSRCWELNP QDRPSFTELR EDLENTLKAL PPAQEPDEIL YVNMDEGGGY PEPPGAAGGA DPPTQPDPKD SCSCLTAAEV HPAGRYVLCP STTPSPAQPA DRGSPAAPGQ EDGA