TIE2_HUMAN
ID TIE2_HUMAN Reviewed; 1124 AA.
AC Q02763; A8K6W0; B4DH20; B4DHD3; D3DRK5; E7EWI2; Q5TCU2; Q8IV34;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 229.
DE RecName: Full=Angiopoietin-1 receptor;
DE EC=2.7.10.1;
DE AltName: Full=Endothelial tyrosine kinase;
DE AltName: Full=Tunica interna endothelial cell kinase;
DE AltName: Full=Tyrosine kinase with Ig and EGF homology domains-2;
DE AltName: Full=Tyrosine-protein kinase receptor TEK;
DE AltName: Full=Tyrosine-protein kinase receptor TIE-2;
DE Short=hTIE2;
DE AltName: Full=p140 TEK;
DE AltName: CD_antigen=CD202b;
DE Flags: Precursor;
GN Name=TEK; Synonyms=TIE2, VMCM, VMCM1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND VARIANT PRO-346.
RC TISSUE=Placenta;
RX PubMed=8382358;
RA Ziegler S.F., Bird T.A., Schneringer J.A., Schooley K.A., Baum P.R.;
RT "Molecular cloning and characterization of a novel receptor protein
RT tyrosine kinase from human placenta.";
RL Oncogene 8:663-670(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP PRO-346.
RC TISSUE=Brain, and Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT PRO-346.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-346.
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 23-37.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [7]
RP FUNCTION AS RECEPTOR FOR ANGPT1 AND ANGPT2, INTERACTION WITH ANGPT1 AND
RP ANGPT2, AND AUTOPHOSPHORYLATION.
RX PubMed=9204896; DOI=10.1126/science.277.5322.55;
RA Maisonpierre P.C., Suri C., Jones P.F., Bartunkova S., Wiegand S.J.,
RA Radziejewski C., Compton D.L., McClain J., Aldrich T.H., Papadopoulos N.,
RA Daly T.J., Davis S., Sato T.N., Yancopoulos G.D.;
RT "Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo
RT angiogenesis.";
RL Science 277:55-60(1997).
RN [8]
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, AND TISSUE SPECIFICITY.
RX PubMed=11806244; DOI=10.1023/a:1012226627813;
RA Reusch P., Barleon B., Weindel K., Martiny-Baron G., Godde A.,
RA Siemeister G., Marme D.;
RT "Identification of a soluble form of the angiopoietin receptor TIE-2
RT released from endothelial cells and present in human blood.";
RL Angiogenesis 4:123-131(2001).
RN [9]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND PHOSPHORYLATION AT TYR-860; TYR-992 AND TYR-1108.
RX PubMed=11513602; DOI=10.1021/bi010959e;
RA Murray B.W., Padrique E.S., Pinko C., McTigue M.A.;
RT "Mechanistic effects of autophosphorylation on receptor tyrosine kinase
RT catalysis: enzymatic characterization of Tie2 and phospho-Tie2.";
RL Biochemistry 40:10243-10253(2001).
RN [10]
RP FUNCTION IN REGULATION OF PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY;
RP ENDOTHELIAL CELL MIGRATION AND REORGANIZATION OF THE ACTIN CYTOSKELETON.
RX PubMed=12816861; DOI=10.1182/blood-2003-03-0670;
RA Cascone I., Audero E., Giraudo E., Napione L., Maniero F., Philips M.R.,
RA Collard J.G., Serini G., Bussolino F.;
RT "Tie-2-dependent activation of RhoA and Rac1 participates in endothelial
RT cell motility triggered by angiopoietin-1.";
RL Blood 102:2482-2490(2003).
RN [11]
RP INTERACTION WITH TNIP2, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF LYS-855.
RX PubMed=12609966; DOI=10.1161/01.res.0000063422.38690.dc;
RA Hughes D.P., Marron M.B., Brindle N.P.;
RT "The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a
RT novel nuclear factor-kappaB inhibitor ABIN-2.";
RL Circ. Res. 92:630-636(2003).
RN [12]
RP FUNCTION IN REGULATION OF ANGIOGENESIS; CELL SURVIVAL; CELL MIGRATION AND
RP ACTIVATION OF AKT1, DOMAIN, AND INTERACTION WITH ANGPT1; ANGPT2 AND ANGPT4.
RX PubMed=15284220; DOI=10.1096/fj.03-1466com;
RA Lee H.J., Cho C.H., Hwang S.J., Choi H.H., Kim K.T., Ahn S.Y., Kim J.H.,
RA Oh J.L., Lee G.M., Koh G.Y.;
RT "Biological characterization of angiopoietin-3 and angiopoietin-4.";
RL FASEB J. 18:1200-1208(2004).
RN [13]
RP FUNCTION AS ANGPT1 RECEPTOR IN PHOSPHORYLATION OF SHC1 AND PIK3R1;
RP REGULATION OF CELL MIGRATION AND ANGIOGENESIS, AUTOPHOSPHORYLATION,
RP MUTAGENESIS OF TYR-1102, PHOSPHORYLATION AT TYR-1102, CATALYTIC ACTIVITY,
RP AND INTERACTION WITH SHC1.
RX PubMed=14665640; DOI=10.1074/jbc.m307456200;
RA Audero E., Cascone I., Maniero F., Napione L., Arese M., Lanfrancone L.,
RA Bussolino F.;
RT "Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates
RT migration and sprouting but not survival of endothelial cells.";
RL J. Biol. Chem. 279:13224-13233(2004).
RN [14]
RP INTERACTION WITH TIE1, SUBCELLULAR LOCATION, FUNCTION AS RECEPTOR FOR
RP ANGPT1 IN PHOSPHORYLATION OF TIE1, AUTOPHOSPHORYLATION, CATALYTIC ACTIVITY,
RP AND MUTAGENESIS OF LYS-855.
RX PubMed=15851516; DOI=10.1083/jcb.200411105;
RA Saharinen P., Kerkela K., Ekman N., Marron M., Brindle N., Lee G.M.,
RA Augustin H., Koh G.Y., Alitalo K.;
RT "Multiple angiopoietin recombinant proteins activate the Tie1 receptor
RT tyrosine kinase and promote its interaction with Tie2.";
RL J. Cell Biol. 169:239-243(2005).
RN [15]
RP FUNCTION AS ANGPT1 RECEPTOR IN ACTIVATION OF AKT1 OR MAPK1/ERK2 AND
RP MAPK3/ERK1; REGULATION OF ENDOTHELIAL CELL MIGRATION AND CELL SPREADING,
RP AND SUBCELLULAR LOCATION.
RX PubMed=18425120; DOI=10.1038/ncb1714;
RA Fukuhara S., Sako K., Minami T., Noda K., Kim H.Z., Kodama T., Shibuya M.,
RA Takakura N., Koh G.Y., Mochizuki N.;
RT "Differential function of Tie2 at cell-cell contacts and cell-substratum
RT contacts regulated by angiopoietin-1.";
RL Nat. Cell Biol. 10:513-526(2008).
RN [16]
RP FUNCTION AS ANGPT1 RECEPTOR IN ACTIVATION OF AKT1 OR MAPK1/ERK2 AND
RP MAPK3/ERK1; REGULATION OF ENDOTHELIAL CELL MIGRATION AND REGULATION OF
RP FOCAL ADHESION ASSEMBLY, INTERACTION WITH TIE1, AUTOPHOSPHORYLATION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18425119; DOI=10.1038/ncb1715;
RA Saharinen P., Eklund L., Miettinen J., Wirkkala R., Anisimov A.,
RA Winderlich M., Nottebaum A., Vestweber D., Deutsch U., Koh G.Y.,
RA Olsen B.R., Alitalo K.;
RT "Angiopoietins assemble distinct Tie2 signalling complexes in endothelial
RT cell-cell and cell-matrix contacts.";
RL Nat. Cell Biol. 10:527-537(2008).
RN [17]
RP PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPRB.
RX PubMed=19116766; DOI=10.1007/s10456-008-9126-0;
RA Yacyshyn O.K., Lai P.F.H., Forse K., Teichert-Kuliszewska K., Jurasz P.,
RA Stewart D.J.;
RT "Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human
RT endothelial cells.";
RL Angiogenesis 12:25-33(2009).
RN [18]
RP INTERACTION WITH CBL, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=19689429; DOI=10.1042/bj20091010;
RA Wehrle C., Van Slyke P., Dumont D.J.;
RT "Angiopoietin-1-induced ubiquitylation of Tie2 by c-Cbl is required for
RT internalization and degradation.";
RL Biochem. J. 423:375-380(2009).
RN [19]
RP INTERACTION WITH PTPRB.
RX PubMed=19451274; DOI=10.1083/jcb.200811159;
RA Winderlich M., Keller L., Cagna G., Broermann A., Kamenyeva O., Kiefer F.,
RA Deutsch U., Nottebaum A.F., Vestweber D.;
RT "VE-PTP controls blood vessel development by balancing Tie-2 activity.";
RL J. Cell Biol. 185:657-671(2009).
RN [20]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-596.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [21]
RP FUNCTION AS RECEPTOR FOR ANGPT1 AND ANGPT2 IN ACTIVATION OF
RP PHOSPHATIDYLINOSITOL 3-KINASE AND AKT1; STIMULATION OF ENDOTHELIAL CELL
RP SURVIVAL AND MIGRATION, CATALYTIC ACTIVITY, AND AUTOPHOSPHORYLATION.
RX PubMed=19223473; DOI=10.1128/mcb.01472-08;
RA Yuan H.T., Khankin E.V., Karumanchi S.A., Parikh S.M.;
RT "Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the
RT endothelium.";
RL Mol. Cell. Biol. 29:2011-2022(2009).
RN [22]
RP REVIEW ON FUNCTION; INTERACTION WITH EFFECTOR AND SCAFFOLDING PROTEINS, AND
RP ROLE IN DISEASE.
RX PubMed=18366015; DOI=10.14670/hh-23.773;
RA Martin V., Liu D., Fueyo J., Gomez-Manzano C.;
RT "Tie2: a journey from normal angiogenesis to cancer and beyond.";
RL Histol. Histopathol. 23:773-780(2008).
RN [23]
RP REVIEW ON SUBCELLULAR LOCATION AND CONTEXT-SPECIFIC SIGNALING.
RX PubMed=19293632; DOI=10.3858/emm.2009.41.3.016;
RA Fukuhara S., Sako K., Noda K., Nagao K., Miura K., Mochizuki N.;
RT "Tie2 is tied at the cell-cell contacts and to extracellular matrix by
RT angiopoietin-1.";
RL Exp. Mol. Med. 41:133-139(2009).
RN [24]
RP REVIEW.
RX PubMed=19234476; DOI=10.1038/nrm2639;
RA Augustin H.G., Koh G.Y., Thurston G., Alitalo K.;
RT "Control of vascular morphogenesis and homeostasis through the
RT angiopoietin-Tie system.";
RL Nat. Rev. Mol. Cell Biol. 10:165-177(2009).
RN [25]
RP REVIEW.
RX PubMed=20054809; DOI=10.14670/hh-25.387;
RA Fukuhara S., Sako K., Noda K., Zhang J., Minami M., Mochizuki N.;
RT "Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and
RT angiogenesis.";
RL Histol. Histopathol. 25:387-396(2010).
RN [26]
RP REVIEW ON SIGNALING, ACTIVITY REGULATION, AND ROLE IN DISEASE.
RX PubMed=20651738; DOI=10.1038/nrc2894;
RA Huang H., Bhat A., Woodnutt G., Lappe R.;
RT "Targeting the ANGPT-TIE2 pathway in malignancy.";
RL Nat. Rev. Cancer 10:575-585(2010).
RN [27]
RP INTERACTION WITH ANGPT2.
RX PubMed=32908006; DOI=10.1126/scitranslmed.aax8013;
RA Leppaenen V.M., Brouillard P., Korhonen E.A., Sipilae T., Jha S.K.,
RA Revencu N., Labarque V., Fastre E., Schloegel M., Ravoet M., Singer A.,
RA Luzzatto C., Angelone D., Crichiutti G., D'Elia A., Kuurne J., Elamaa H.,
RA Koh G.Y., Saharinen P., Vikkula M., Alitalo K.;
RT "Characterization of ANGPT2 mutations associated with primary lymphedema.";
RL Sci. Transl. Med. 12:0-0(2020).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 808-1124, ACTIVE SITE, ACTIVITY
RP REGULATION, AND PREDICTION OF ATP-BINDING REGION.
RX PubMed=11080633; DOI=10.1016/s0969-2126(00)00516-5;
RA Shewchuk L.M., Hassell A.M., Ellis B., Holmes W.D., Davis R., Horne E.L.,
RA Kadwell S.H., McKee D.D., Moore J.T.;
RT "Structure of the Tie2 RTK domain: self-inhibition by the nucleotide
RT binding loop, activation loop, and C-terminal tail.";
RL Structure 8:1105-1113(2000).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 23-445 ALONE AND IN COMPLEX WITH
RP ANGPT2, GLYCOSYLATION AT ASN-140, AND DISULFIDE BONDS.
RX PubMed=16732286; DOI=10.1038/nsmb1101;
RA Barton W.A., Tzvetkova-Robev D., Miranda E.P., Kolev M.V.,
RA Rajashankar K.R., Himanen J.P., Nikolov D.B.;
RT "Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-
RT Tie2 complex.";
RL Nat. Struct. Mol. Biol. 13:524-532(2006).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 808-1124 IN COMPLEX WITH TRIAZINE
RP DERIVATIVE, AND ACTIVITY REGULATION.
RX PubMed=17350837; DOI=10.1016/j.bmcl.2007.02.067;
RA Hodous B.L., Geuns-Meyer S.D., Hughes P.E., Albrecht B.K., Bellon S.,
RA Caenepeel S., Cee V.J., Chaffee S.C., Emery M., Fretland J., Gallant P.,
RA Gu Y., Johnson R.E., Kim J.L., Long A.M., Morrison M., Olivieri P.R.,
RA Patel V.F., Polverino A., Rose P., Wang L., Zhao H.;
RT "Synthesis, structural analysis, and SAR studies of triazine derivatives as
RT potent, selective Tie-2 inhibitors.";
RL Bioorg. Med. Chem. Lett. 17:2886-2889(2007).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 808-1124 IN COMPLEX WITH TRIAZINE
RP DERIVATIVE, AND ACTIVITY REGULATION.
RX PubMed=17253678; DOI=10.1021/jm061107l;
RA Hodous B.L., Geuns-Meyer S.D., Hughes P.E., Albrecht B.K., Bellon S.,
RA Bready J., Caenepeel S., Cee V.J., Chaffee S.C., Coxon A., Emery M.,
RA Fretland J., Gallant P., Gu Y., Hoffman D., Johnson R.E., Kendall R.,
RA Kim J.L., Long A.M., Morrison M., Olivieri P.R., Patel V.F., Polverino A.,
RA Rose P., Tempest P., Wang L., Whittington D.A., Zhao H.;
RT "Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine
RT Tie-2 kinase inhibitor.";
RL J. Med. Chem. 50:611-626(2007).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 802-1124 IN COMPLEX WITH
RP THIAZOLOPYRIMIDINE DERIVATIVE, AND ACTIVITY REGULATION.
RX PubMed=19854647; DOI=10.1016/j.bmcl.2009.10.001;
RA Luke R.W., Ballard P., Buttar D., Campbell L., Curwen J., Emery S.C.,
RA Griffen A.M., Hassall L., Hayter B.R., Jones C.D., McCoull W., Mellor M.,
RA Swain M.L., Tucker J.A.;
RT "Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with
RT activity against Tie-2 in vitro and in vivo.";
RL Bioorg. Med. Chem. Lett. 19:6670-6674(2009).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 808-1124 IN COMPLEX WITH
RP CEP11207.
RA Fedorov A.A., Fedorov E.V., Pauletti D., Meyer S.L., Hudkins R.L.,
RA Almo S.C.;
RT "Crystal structure of cytoplasmic kinase domain of Tie2 complexed with
RT inhibitor CEP11207.";
RL Submitted (JAN-2010) to the PDB data bank.
RN [34]
RP VARIANT VMCM TRP-849.
RX PubMed=8980225; DOI=10.1016/s0092-8674(00)81814-0;
RA Vikkula M., Boon L.M., Carraway K.L. III, Calvert J.T., Diamonti A.J.,
RA Goumnerov B., Pasyk K.A., Marchuk D.A., Warman M.L., Cantley L.C.,
RA Mulliken J.B., Olse B.R.;
RT "Vascular dysmorphogenesis caused by an activating mutation in the receptor
RT tyrosine kinase TIE2.";
RL Cell 87:1181-1190(1996).
RN [35]
RP VARIANTS VMCM TRP-849 AND SER-897.
RX PubMed=10369874; DOI=10.1093/hmg/8.7.1279;
RA Calvert J.T., Riney T.J., Kontos C.D., Cha E.H., Prieto V.G., Shea C.R.,
RA Berg J.N., Nevin N.C., Simpson S.A., Pasyk K.A., Speer M.C., Peters K.G.,
RA Marchuk D.A.;
RT "Allelic and locus heterogeneity in inherited venous malformations.";
RL Hum. Mol. Genet. 8:1279-1289(1999).
RN [36]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-117.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [37]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-117; THR-148; VAL-226; ILE-486;
RP LEU-600; PHE-634; ILE-676; THR-724; ALA-883 AND VAL-1124.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [38]
RP INVOLVEMENT IN VMCM, INVOLVEMENT IN DISEASE, SUBCELLULAR LOCATION,
RP CHARACTERIZATION OF VARIANTS VMCM TRP-849, VARIANTS HIS-897; PHE-897;
RP SER-897; PHE-914; CYS-915; LEU-915 AND ILE-917, CHARACTERIZATION OF
RP VARIANTS HIS-897; PHE-897; SER-897; PHE-914; CYS-915; LEU-915 AND ILE-917,
RP AND PHOSPHORYLATION AT TYR-1102.
RX PubMed=19079259; DOI=10.1038/ng.272;
RA Limaye N., Wouters V., Uebelhoer M., Tuominen M., Wirkkala R.,
RA Mulliken J.B., Eklund L., Boon L.M., Vikkula M.;
RT "Somatic mutations in angiopoietin receptor gene TEK cause solitary and
RT multiple sporadic venous malformations.";
RL Nat. Genet. 41:118-124(2009).
RN [39]
RP VARIANTS VMCM TRP-849; CYS-897; HIS-915; CYS-918; LEU-919; SER-925 AND
RP ASN-1100, AND CHARACTERIZATION OF VARIANTS VMCM TRP-849; SER-897; HIS-915;
RP CYS-918; LEU-919; SER-925 AND ASN-1100.
RX PubMed=19888299; DOI=10.1038/ejhg.2009.193;
RA Wouters V., Limaye N., Uebelhoer M., Irrthum A., Boon L.M., Mulliken J.B.,
RA Enjolras O., Baselga E., Berg J., Dompmartin A., Ivarsson S.A., Kangesu L.,
RA Lacassie Y., Murphy J., Teebi A.S., Penington A., Rieu P., Vikkula M.;
RT "Hereditary cutaneomucosal venous malformations are caused by TIE2
RT mutations with widely variable hyper-phosphorylating effects.";
RL Eur. J. Hum. Genet. 18:414-420(2010).
RN [40]
RP INVOLVEMENT IN GLC3E, VARIANTS GLC3E 19-THR--ARG-210 DEL; TYR-233; ASN-294
RP AND CYS-611, CHARACTERIZATION OF VARIANTS GLC3E 19-THR--ARG-210 DEL;
RP TYR-233; ASN-294 AND CYS-611, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP CYS-224.
RX PubMed=27270174; DOI=10.1172/jci85830;
RA Souma T., Tompson S.W., Thomson B.R., Siggs O.M., Kizhatil K.,
RA Yamaguchi S., Feng L., Limviphuvadh V., Whisenhunt K.N., Maurer-Stroh S.,
RA Yanovitch T.L., Kalaydjieva L., Azmanov D.N., Finzi S., Mauri L.,
RA Javadiyan S., Souzeau E., Zhou T., Hewitt A.W., Kloss B., Burdon K.P.,
RA Mackey D.A., Allen K.F., Ruddle J.B., Lim S.H., Rozen S., Tran-Viet K.N.,
RA Liu X., John S., Wiggs J.L., Pasutto F., Craig J.E., Jin J., Quaggin S.E.,
RA Young T.L.;
RT "Angiopoietin receptor TEK mutations underlie primary congenital glaucoma
RT with variable expressivity.";
RL J. Clin. Invest. 126:2575-2587(2016).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial
CC cell survival, proliferation, migration, adhesion and cell spreading,
CC reorganization of the actin cytoskeleton, but also maintenance of
CC vascular quiescence. Has anti-inflammatory effects by preventing the
CC leakage of pro-inflammatory plasma proteins and leukocytes from blood
CC vessels. Required for normal angiogenesis and heart development during
CC embryogenesis. Required for post-natal hematopoiesis. After birth,
CC activates or inhibits angiogenesis, depending on the context. Inhibits
CC angiogenesis and promotes vascular stability in quiescent vessels,
CC where endothelial cells have tight contacts. In quiescent vessels,
CC ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes
CC with TEK molecules from adjoining cells, and this leads to preferential
CC activation of phosphatidylinositol 3-kinase and the AKT1 signaling
CC cascades. In migrating endothelial cells that lack cell-cell adhesions,
CC ANGT1 recruits TEK to contacts with the extracellular matrix, leading
CC to the formation of focal adhesion complexes, activation of PTK2/FAK
CC and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately
CC to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers
CC receptor dimerization and autophosphorylation at specific tyrosine
CC residues that then serve as binding sites for scaffold proteins and
CC effectors. Signaling is modulated by ANGPT2 that has lower affinity for
CC TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but
CC inhibits ANGPT1-mediated signaling by competing for the same binding
CC site. Signaling is also modulated by formation of heterodimers with
CC TIE1, and by proteolytic processing that gives rise to a soluble TEK
CC extracellular domain. The soluble extracellular domain modulates
CC signaling by functioning as decoy receptor for angiopoietins. TEK
CC phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1.
CC {ECO:0000269|PubMed:12816861, ECO:0000269|PubMed:14665640,
CC ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516,
CC ECO:0000269|PubMed:18366015, ECO:0000269|PubMed:18425119,
CC ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19223473,
CC ECO:0000269|PubMed:20651738, ECO:0000269|PubMed:9204896}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:11513602, ECO:0000269|PubMed:12609966,
CC ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15851516,
CC ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:8382358};
CC -!- ACTIVITY REGULATION: Angiopoietin binding leads to receptor
CC dimerization and activation by autophosphorylation at Tyr-992 on the
CC kinase activation loop. Inhibited by staurosporine, K252a, PP2,
CC damnacanthal, SB203580, CEP-11207, CEP-11981 and CE-245677. Inhibited
CC by triazine, thienopyrimidine and thiazolopyrimidine derivatives.
CC {ECO:0000269|PubMed:11080633, ECO:0000269|PubMed:11513602,
CC ECO:0000269|PubMed:17253678, ECO:0000269|PubMed:17350837,
CC ECO:0000269|PubMed:19854647, ECO:0000269|PubMed:20651738}.
CC -!- SUBUNIT: Homodimer. Heterodimer with TIE1. Interacts with ANGPT1,
CC ANGPT2 and ANGPT4 (PubMed:9204896, PubMed:15284220, PubMed:32908006).
CC At cell-cell contacts in quiescent cells, forms a signaling complex
CC composed of ANGPT1 plus TEK molecules from two adjoining cells. In the
CC absence of endothelial cell-cell contacts, interaction with ANGPT1
CC mediates contacts with the extracellular matrix. Interacts with PTPRB;
CC this promotes endothelial cell-cell adhesion. Interacts with DOK2,
CC GRB2, GRB7, GRB14, PIK3R1 and PTPN11/SHP2. Colocalizes with DOK2 at
CC contacts with the extracellular matrix in migrating cells. Interacts
CC (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine
CC phosphorylated) with SHC1 (via SH2 domain).
CC {ECO:0000269|PubMed:12609966, ECO:0000269|PubMed:14665640,
CC ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516,
CC ECO:0000269|PubMed:16732286, ECO:0000269|PubMed:17253678,
CC ECO:0000269|PubMed:17350837, ECO:0000269|PubMed:18425119,
CC ECO:0000269|PubMed:19451274, ECO:0000269|PubMed:19689429,
CC ECO:0000269|PubMed:19854647, ECO:0000269|PubMed:32908006,
CC ECO:0000269|PubMed:9204896, ECO:0000269|Ref.33}.
CC -!- INTERACTION:
CC Q02763; Q15389: ANGPT1; NbExp=2; IntAct=EBI-2257090, EBI-2922365;
CC Q02763; O15123: ANGPT2; NbExp=4; IntAct=EBI-2257090, EBI-2912111;
CC Q02763; O15123-1: ANGPT2; NbExp=5; IntAct=EBI-2257090, EBI-15552475;
CC Q02763; Q16678: CYP1B1; NbExp=6; IntAct=EBI-2257090, EBI-1055133;
CC Q02763; Q05209: PTPN12; NbExp=2; IntAct=EBI-2257090, EBI-2266035;
CC Q02763; P23467: PTPRB; NbExp=3; IntAct=EBI-2257090, EBI-1265766;
CC Q02763; P08575: PTPRC; NbExp=3; IntAct=EBI-2257090, EBI-1341;
CC Q02763; Q12913: PTPRJ; NbExp=2; IntAct=EBI-2257090, EBI-2264500;
CC Q02763; Q15262: PTPRK; NbExp=2; IntAct=EBI-2257090, EBI-474052;
CC Q02763; Q16827: PTPRO; NbExp=2; IntAct=EBI-2257090, EBI-723739;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18425119,
CC ECO:0000269|PubMed:18425120, ECO:0000269|PubMed:19079259,
CC ECO:0000269|PubMed:27270174}; Single-pass type I membrane protein. Cell
CC junction {ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120,
CC ECO:0000269|PubMed:27270174}. Cell junction, focal adhesion
CC {ECO:0000305|PubMed:19293632}. Cytoplasm, cytoskeleton. Secreted
CC {ECO:0000269|PubMed:11806244}. Note=Recruited to cell-cell contacts in
CC quiescent endothelial cells (PubMed:18425120, PubMed:18425119).
CC Colocalizes with the actin cytoskeleton and at actin stress fibers
CC during cell spreading. Recruited to the lower surface of migrating
CC cells, especially the rear end of the cell. Proteolytic processing
CC gives rise to a soluble extracellular domain that is secreted
CC (PubMed:11806244). {ECO:0000269|PubMed:11806244,
CC ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:18425120}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q02763-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q02763-2; Sequence=VSP_042138;
CC Name=3;
CC IsoId=Q02763-3; Sequence=VSP_042137, VSP_042138, VSP_042139;
CC -!- TISSUE SPECIFICITY: Detected in umbilical vein endothelial cells.
CC Proteolytic processing gives rise to a soluble extracellular domain
CC that is detected in blood plasma (at protein level). Predominantly
CC expressed in endothelial cells and their progenitors, the angioblasts.
CC Has been directly found in placenta and lung, with a lower level in
CC umbilical vein endothelial cells, brain and kidney.
CC {ECO:0000269|PubMed:11806244, ECO:0000269|PubMed:8382358}.
CC -!- DOMAIN: The soluble extracellular domain is functionally active in
CC angiopoietin binding and can modulate the activity of the membrane-
CC bound form by competing for angiopoietins.
CC {ECO:0000269|PubMed:15284220}.
CC -!- PTM: Proteolytic processing leads to the shedding of the extracellular
CC domain (soluble TIE-2 alias sTIE-2). {ECO:0000269|PubMed:11806244}.
CC -!- PTM: Autophosphorylated on tyrosine residues in response to ligand
CC binding. Autophosphorylation occurs in trans, i.e. one subunit of the
CC dimeric receptor phosphorylates tyrosine residues on the other subunit.
CC Autophosphorylation occurs in a sequential manner, where Tyr-992 in the
CC kinase activation loop is phosphorylated first, followed by
CC autophosphorylation at Tyr-1108 and at additional tyrosine residues.
CC ANGPT1-induced phosphorylation is impaired during hypoxia, due to
CC increased expression of ANGPT2. Phosphorylation is important for
CC interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1102
CC is important for interaction with SHC1, GRB2 and GRB7. Phosphorylation
CC at Tyr-1108 is important for interaction with DOK2 and for coupling to
CC downstream signal transduction pathways in endothelial cells.
CC Dephosphorylated by PTPRB. {ECO:0000269|PubMed:11513602,
CC ECO:0000269|PubMed:14665640}.
CC -!- PTM: Ubiquitinated. The phosphorylated receptor is ubiquitinated and
CC internalized, leading to its degradation.
CC {ECO:0000269|PubMed:19689429}.
CC -!- DISEASE: Dominantly inherited venous malformations (VMCM) [MIM:600195]:
CC An error of vascular morphogenesis characterized by dilated,
CC serpiginous channels. {ECO:0000269|PubMed:10369874,
CC ECO:0000269|PubMed:19079259, ECO:0000269|PubMed:19888299,
CC ECO:0000269|PubMed:8980225}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Somatic mutations of TEK are associated with solitary and
CC multiple sporadic venous malformations. {ECO:0000269|PubMed:19079259}.
CC -!- DISEASE: Note=May play a role in a range of diseases with a vascular
CC component, including neovascularization of tumors, psoriasis and
CC inflammation.
CC -!- DISEASE: Glaucoma 3, primary congenital, E (GLC3E) [MIM:617272]: An
CC autosomal dominant form of primary congenital glaucoma (PCG). PCG is
CC characterized by marked increase of intraocular pressure at birth or
CC early childhood, large ocular globes (buphthalmos) and corneal edema.
CC It results from developmental defects of the trabecular meshwork and
CC anterior chamber angle of the eye that prevent adequate drainage of
CC aqueous humor. {ECO:0000269|PubMed:27270174}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Tie subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TEKID42517ch9p21.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L06139; AAA61139.1; -; mRNA.
DR EMBL; AK291775; BAF84464.1; -; mRNA.
DR EMBL; AK294887; BAG57981.1; -; mRNA.
DR EMBL; AK295043; BAG58094.1; -; mRNA.
DR EMBL; AL133411; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355432; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58571.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58572.1; -; Genomic_DNA.
DR EMBL; BC035514; AAH35514.2; -; mRNA.
DR CCDS; CCDS6519.1; -. [Q02763-1]
DR CCDS; CCDS75825.1; -. [Q02763-2]
DR CCDS; CCDS78389.1; -. [Q02763-3]
DR PIR; I58388; I58388.
DR RefSeq; NP_000450.2; NM_000459.4. [Q02763-1]
DR RefSeq; NP_001277006.1; NM_001290077.1.
DR RefSeq; NP_001277007.1; NM_001290078.1.
DR PDB; 1FVR; X-ray; 2.20 A; A/B=808-1124.
DR PDB; 2GY5; X-ray; 2.90 A; A=23-445.
DR PDB; 2GY7; X-ray; 3.70 A; B=23-445.
DR PDB; 2OO8; X-ray; 2.20 A; X=808-1124.
DR PDB; 2OSC; X-ray; 2.80 A; A=808-1124.
DR PDB; 2P4I; X-ray; 2.50 A; A/B=808-1124.
DR PDB; 2WQB; X-ray; 2.95 A; A=802-1124.
DR PDB; 3BEA; X-ray; 2.02 A; A=917-935.
DR PDB; 3L8P; X-ray; 2.40 A; A=808-1124.
DR PDB; 4K0V; X-ray; 4.51 A; A=23-542.
DR PDB; 4X3J; X-ray; 2.50 A; A=802-1122.
DR PDB; 5MYA; X-ray; 2.90 A; A/B=443-742.
DR PDB; 5MYB; X-ray; 2.60 A; A/B=443-742.
DR PDB; 5UTK; X-ray; 2.50 A; A/B=442-741.
DR PDB; 6MWE; X-ray; 2.05 A; A/B=808-1124.
DR PDB; 7E72; X-ray; 2.09 A; E/F=541-735.
DR PDBsum; 1FVR; -.
DR PDBsum; 2GY5; -.
DR PDBsum; 2GY7; -.
DR PDBsum; 2OO8; -.
DR PDBsum; 2OSC; -.
DR PDBsum; 2P4I; -.
DR PDBsum; 2WQB; -.
DR PDBsum; 3BEA; -.
DR PDBsum; 3L8P; -.
DR PDBsum; 4K0V; -.
DR PDBsum; 4X3J; -.
DR PDBsum; 5MYA; -.
DR PDBsum; 5MYB; -.
DR PDBsum; 5UTK; -.
DR PDBsum; 6MWE; -.
DR PDBsum; 7E72; -.
DR AlphaFoldDB; Q02763; -.
DR SMR; Q02763; -.
DR BioGRID; 112869; 25.
DR DIP; DIP-6047N; -.
DR IntAct; Q02763; 28.
DR MINT; Q02763; -.
DR STRING; 9606.ENSP00000369375; -.
DR BindingDB; Q02763; -.
DR ChEMBL; CHEMBL4128; -.
DR DrugBank; DB00415; Ampicillin.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB08221; N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE.
DR DrugBank; DB08901; Ponatinib.
DR DrugBank; DB08896; Regorafenib.
DR DrugBank; DB14840; Ripretinib.
DR DrugBank; DB11800; Tivozanib.
DR DrugBank; DB05294; Vandetanib.
DR DrugCentral; Q02763; -.
DR GuidetoPHARMACOLOGY; 1842; -.
DR GlyConnect; 769; 10 N-Linked glycans (5 sites).
DR GlyGen; Q02763; 10 sites, 11 N-linked glycans (5 sites).
DR iPTMnet; Q02763; -.
DR PhosphoSitePlus; Q02763; -.
DR BioMuta; TEK; -.
DR DMDM; 218511853; -.
DR EPD; Q02763; -.
DR MassIVE; Q02763; -.
DR PaxDb; Q02763; -.
DR PeptideAtlas; Q02763; -.
DR PRIDE; Q02763; -.
DR ProteomicsDB; 58121; -. [Q02763-1]
DR ProteomicsDB; 58122; -. [Q02763-2]
DR ProteomicsDB; 58123; -. [Q02763-3]
DR ABCD; Q02763; 9 sequenced antibodies.
DR Antibodypedia; 2050; 1376 antibodies from 44 providers.
DR DNASU; 7010; -.
DR Ensembl; ENST00000380036.10; ENSP00000369375.4; ENSG00000120156.22. [Q02763-1]
DR Ensembl; ENST00000406359.8; ENSP00000383977.4; ENSG00000120156.22. [Q02763-2]
DR Ensembl; ENST00000519097.5; ENSP00000430686.1; ENSG00000120156.22. [Q02763-3]
DR GeneID; 7010; -.
DR KEGG; hsa:7010; -.
DR MANE-Select; ENST00000380036.10; ENSP00000369375.4; NM_000459.5; NP_000450.3.
DR UCSC; uc003zqi.5; human. [Q02763-1]
DR CTD; 7010; -.
DR DisGeNET; 7010; -.
DR GeneCards; TEK; -.
DR GeneReviews; TEK; -.
DR HGNC; HGNC:11724; TEK.
DR HPA; ENSG00000120156; Tissue enhanced (placenta).
DR MalaCards; TEK; -.
DR MIM; 600195; phenotype.
DR MIM; 600221; gene.
DR MIM; 617272; phenotype.
DR neXtProt; NX_Q02763; -.
DR OpenTargets; ENSG00000120156; -.
DR Orphanet; 1059; Blue rubber bleb nevus.
DR Orphanet; 98976; Congenital glaucoma.
DR Orphanet; 2451; Mucocutaneous venous malformations.
DR PharmGKB; PA36441; -.
DR VEuPathDB; HostDB:ENSG00000120156; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000158840; -.
DR HOGENOM; CLU_008888_0_0_1; -.
DR InParanoid; Q02763; -.
DR OMA; PEGITLF; -.
DR OrthoDB; 707342at2759; -.
DR PhylomeDB; Q02763; -.
DR TreeFam; TF317568; -.
DR BRENDA; 2.7.10.1; 2681.
DR PathwayCommons; Q02763; -.
DR Reactome; R-HSA-210993; Tie2 Signaling.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR SignaLink; Q02763; -.
DR SIGNOR; Q02763; -.
DR BioGRID-ORCS; 7010; 3 hits in 1105 CRISPR screens.
DR ChiTaRS; TEK; human.
DR EvolutionaryTrace; Q02763; -.
DR GeneWiki; TEK_tyrosine_kinase; -.
DR GenomeRNAi; 7010; -.
DR Pharos; Q02763; Tclin.
DR PRO; PR:Q02763; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q02763; protein.
DR Bgee; ENSG00000120156; Expressed in right lung and 154 other tissues.
DR ExpressionAtlas; Q02763; baseline and differential.
DR Genevisible; Q02763; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0060216; P:definitive hemopoiesis; TAS:UniProtKB.
DR GO; GO:0001935; P:endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0072012; P:glomerulus vasculature development; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0060347; P:heart trabecula formation; ISS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; TAS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; TAS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IMP:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:2000351; P:regulation of endothelial cell apoptotic process; TAS:UniProtKB.
DR GO; GO:0032878; P:regulation of establishment or maintenance of cell polarity; IMP:UniProtKB.
DR GO; GO:0043114; P:regulation of vascular permeability; TAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0002040; P:sprouting angiogenesis; IMP:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IMP:UniProtKB.
DR GO; GO:0048014; P:Tie signaling pathway; IDA:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IDA:UniProtKB.
DR CDD; cd00055; EGF_Lam; 2.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 2.60.40.10; -; 6.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002049; LE_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR018941; Tyr_kin_Tie2_Ig-like_dom-1_N.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF00041; fn3; 3.
DR Pfam; PF10430; Ig_Tie2_1; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00181; EGF; 3.
DR SMART; SM00060; FN3; 3.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF49265; SSF49265; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00022; EGF_1; 3.
DR PROSITE; PS01186; EGF_2; 3.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS50853; FN3; 3.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; ATP-binding;
KW Cell junction; Cell membrane; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW EGF-like domain; Glaucoma; Glycoprotein; Immunoglobulin domain; Kinase;
KW Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 23..1124
FT /note="Angiopoietin-1 receptor"
FT /id="PRO_0000024474"
FT TOPO_DOM 23..748
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 749..769
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 770..1124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 44..123
FT /note="Ig-like C2-type 1"
FT DOMAIN 210..252
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 254..299
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 301..341
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 350..440
FT /note="Ig-like C2-type 2"
FT DOMAIN 447..541
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 545..636
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 641..735
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 824..1096
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 964
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:11080633"
FT BINDING 830..838
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT BINDING 855
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 860
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11513602"
FT MOD_RES 992
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11513602"
FT MOD_RES 1102
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:14665640,
FT ECO:0000269|PubMed:27270174"
FT MOD_RES 1108
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11513602"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16732286"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 399
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 438
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 560
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 596
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 649
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 691
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..102
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 211..220
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 224..233
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 227..240
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 242..251
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 255..264
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 268..274
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 280..287
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 289..298
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 302..311
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 315..323
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 317..329
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 331..340
FT /evidence="ECO:0000269|PubMed:16732286"
FT DISULFID 370..424
FT /evidence="ECO:0000269|PubMed:16732286"
FT VAR_SEQ 18..121
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042137"
FT VAR_SEQ 300..342
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042138"
FT VAR_SEQ 788
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042139"
FT VARIANT 19..210
FT /note="Missing (in GLC3E; formation of protein aggregates)"
FT /evidence="ECO:0000269|PubMed:27270174"
FT /id="VAR_078045"
FT VARIANT 117
FT /note="K -> N (in breast cancer samples; infiltrating
FT ductal carcinoma; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:16959974,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_035714"
FT VARIANT 148
FT /note="I -> T (in dbSNP:rs35969327)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041855"
FT VARIANT 226
FT /note="A -> V (in dbSNP:rs35814893)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041856"
FT VARIANT 233
FT /note="C -> Y (in GLC3E; enhanced proteasomal degradation)"
FT /evidence="ECO:0000269|PubMed:27270174"
FT /id="VAR_078046"
FT VARIANT 294
FT /note="K -> N (in GLC3E; unknown pathological significance;
FT 10-fold decrease of Tyr-1102 phosphorylation; no effect on
FT membrane location; dbSNP:rs146169480)"
FT /evidence="ECO:0000269|PubMed:27270174"
FT /id="VAR_078047"
FT VARIANT 346
FT /note="Q -> P (in dbSNP:rs682632)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8382358,
FT ECO:0000269|Ref.4"
FT /id="VAR_048002"
FT VARIANT 391
FT /note="T -> I (in dbSNP:rs34032300)"
FT /id="VAR_048003"
FT VARIANT 486
FT /note="V -> I (in dbSNP:rs1334811)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_024578"
FT VARIANT 600
FT /note="V -> L (in dbSNP:rs35030851)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041857"
FT VARIANT 611
FT /note="Y -> C (in GLC3E; reduced response to ligand; loss
FT of ligand-induced phosphorylation; no effect on basal
FT membrane location; dbSNP:rs1306527531)"
FT /evidence="ECO:0000269|PubMed:27270174"
FT /id="VAR_078048"
FT VARIANT 634
FT /note="L -> F (in dbSNP:rs35378598)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041858"
FT VARIANT 676
FT /note="V -> I (in dbSNP:rs56367117)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041859"
FT VARIANT 724
FT /note="A -> T (in dbSNP:rs4631561)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041860"
FT VARIANT 849
FT /note="R -> W (in VMCM; increased ligand-independent
FT autophosphorylation and kinase activation; no effect on
FT location at membrane; dbSNP:rs80338908)"
FT /evidence="ECO:0000269|PubMed:10369874,
FT ECO:0000269|PubMed:19079259, ECO:0000269|PubMed:19888299,
FT ECO:0000269|PubMed:8980225"
FT /id="VAR_006352"
FT VARIANT 883
FT /note="P -> A (in an ovarian serous carcinoma sample;
FT somatic mutation; dbSNP:rs1490428165)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041861"
FT VARIANT 897
FT /note="Y -> C (in VMCM; increased ligand-independent
FT autophosphorylation and kinase activation;
FT dbSNP:rs80338909)"
FT /evidence="ECO:0000269|PubMed:19888299"
FT /id="VAR_066606"
FT VARIANT 897
FT /note="Y -> F (found in a patient with multiple sporadic
FT venous malformations; increased ligand-independent
FT autophosphorylation; the hyperphosphorylation increases
FT when associated with Leu-915)"
FT /evidence="ECO:0000269|PubMed:19079259"
FT /id="VAR_078049"
FT VARIANT 897
FT /note="Y -> H (found in a patient with solitary sporadic
FT venous malformations; increased ligand-independent
FT autophosphorylation)"
FT /evidence="ECO:0000269|PubMed:19079259"
FT /id="VAR_078050"
FT VARIANT 897
FT /note="Y -> S (in VMCM; also found in a patient with
FT solitary sporadic venous malformations; increased ligand-
FT independent autophosphorylation and kinase activation;
FT dbSNP:rs80338909)"
FT /evidence="ECO:0000269|PubMed:10369874,
FT ECO:0000269|PubMed:19079259, ECO:0000269|PubMed:19888299"
FT /id="VAR_008716"
FT VARIANT 914
FT /note="L -> F (found in patients with solitary and multiple
FT sporadic venous malformations; increased ligand-independent
FT autophosphorylation; novel location at endoplasmic
FT reticulum and Golgi apparatus; partially retained at
FT endoplasmic reticulum and Golgi apparatus)"
FT /evidence="ECO:0000269|PubMed:19079259"
FT /id="VAR_078051"
FT VARIANT 915
FT /note="R -> C (found in a patient with solitary sporadic
FT venous malformations; increased ligand-independent
FT autophosphorylation)"
FT /evidence="ECO:0000269|PubMed:19079259"
FT /id="VAR_078052"
FT VARIANT 915
FT /note="R -> H (in VMCM; strongly increased ligand-
FT independent autophosphorylation and kinase activation;
FT dbSNP:rs387906745)"
FT /evidence="ECO:0000269|PubMed:19888299"
FT /id="VAR_066607"
FT VARIANT 915
FT /note="R -> L (found in a patient with multiple sporadic
FT venous malformations; increased ligand-independent
FT autophosphorylation; the autophosphorylation increases when
FT associated with Phe-897)"
FT /evidence="ECO:0000269|PubMed:19079259"
FT /id="VAR_078053"
FT VARIANT 917
FT /note="S -> I (found in a patient with solitary sporadic
FT venous malformations; increased ligand-independent
FT autophosphorylation)"
FT /evidence="ECO:0000269|PubMed:19079259"
FT /id="VAR_078054"
FT VARIANT 918
FT /note="R -> C (in VMCM; strongly increased ligand-
FT independent autophosphorylation and kinase activation)"
FT /evidence="ECO:0000269|PubMed:19888299"
FT /id="VAR_066608"
FT VARIANT 919
FT /note="V -> L (in VMCM; increased ligand-independent
FT autophosphorylation and kinase activation)"
FT /evidence="ECO:0000269|PubMed:19888299"
FT /id="VAR_066609"
FT VARIANT 925
FT /note="A -> S (in VMCM; increased ligand-independent
FT autophosphorylation and kinase activation)"
FT /evidence="ECO:0000269|PubMed:19888299"
FT /id="VAR_066610"
FT VARIANT 1100
FT /note="K -> N (in VMCM; strongly increased ligand-
FT independent autophosphorylation and kinase activation)"
FT /evidence="ECO:0000269|PubMed:19888299"
FT /id="VAR_066611"
FT VARIANT 1124
FT /note="A -> V (in a renal clear cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041862"
FT MUTAGEN 224
FT /note="C->S: Reduces protein abundance."
FT /evidence="ECO:0000269|PubMed:27270174"
FT MUTAGEN 855
FT /note="K->R: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12609966,
FT ECO:0000269|PubMed:15851516"
FT MUTAGEN 1102
FT /note="Y->F: Abolishes interaction with SHC1."
FT /evidence="ECO:0000269|PubMed:14665640"
FT CONFLICT 536
FT /note="F -> L (in Ref. 2; BAG58094)"
FT /evidence="ECO:0000305"
FT CONFLICT 695
FT /note="T -> I (in Ref. 1; AAA61139)"
FT /evidence="ECO:0000305"
FT CONFLICT 939..940
FT /note="QQ -> HH (in Ref. 5; AAH35514)"
FT /evidence="ECO:0000305"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 40..46
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:2GY5"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 80..88
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 98..106
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 109..119
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 139..145
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 160..165
FT /evidence="ECO:0007829|PDB:2GY5"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:2GY5"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 187..193
FT /evidence="ECO:0007829|PDB:2GY5"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 202..208
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 215..217
FT /evidence="ECO:0007829|PDB:2GY5"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:2GY5"
FT TURN 271..276
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:2GY5"
FT TURN 282..285
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:2GY5"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:2GY5"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 361..366
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 369..373
FT /evidence="ECO:0007829|PDB:2GY5"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 396..400
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 405..408
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 411..414
FT /evidence="ECO:0007829|PDB:2GY5"
FT HELIX 416..418
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 420..428
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 431..439
FT /evidence="ECO:0007829|PDB:2GY5"
FT STRAND 446..449
FT /evidence="ECO:0007829|PDB:5UTK"
FT STRAND 452..456
FT /evidence="ECO:0007829|PDB:5UTK"
FT STRAND 461..464
FT /evidence="ECO:0007829|PDB:5UTK"
FT STRAND 469..472
FT /evidence="ECO:0007829|PDB:5UTK"
FT STRAND 476..485
FT /evidence="ECO:0007829|PDB:5UTK"
FT STRAND 493..504
FT /evidence="ECO:0007829|PDB:5UTK"
FT STRAND 512..521
FT /evidence="ECO:0007829|PDB:5UTK"
FT STRAND 534..537
FT /evidence="ECO:0007829|PDB:5UTK"
FT STRAND 550..555
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 558..562
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 569..572
FT /evidence="ECO:0007829|PDB:5MYA"
FT STRAND 575..585
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 588..594
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 598..602
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 610..621
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 629..632
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 643..648
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 655..660
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 663..665
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 669..677
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 683..689
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 696..699
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 707..715
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 727..730
FT /evidence="ECO:0007829|PDB:7E72"
FT STRAND 816..818
FT /evidence="ECO:0007829|PDB:1FVR"
FT HELIX 821..823
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 824..833
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 836..845
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 848..857
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 864..866
FT /evidence="ECO:0007829|PDB:2P4I"
FT HELIX 872..879
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 888..894
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 897..903
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 910..916
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 919..922
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 924..929
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 932..936
FT /evidence="ECO:0007829|PDB:2OO8"
FT HELIX 938..957
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 967..969
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 970..972
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 974..976
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 978..980
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 985..987
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1000..1004
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1007..1012
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1017..1032
FT /evidence="ECO:0007829|PDB:6MWE"
FT TURN 1038..1041
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1044..1050
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1051..1053
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1065..1074
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1079..1081
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1085..1097
FT /evidence="ECO:0007829|PDB:6MWE"
FT STRAND 1098..1100
FT /evidence="ECO:0007829|PDB:6MWE"
FT HELIX 1118..1120
FT /evidence="ECO:0007829|PDB:6MWE"
SQ SEQUENCE 1124 AA; 125830 MW; E739DEC3E4FEB124 CRC64;
MDSLASLVLC GVSLLLSGTV EGAMDLILIN SLPLVSDAET SLTCIASGWR PHEPITIGRD
FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY FCEGRVRGEA IRIRTMKMRQ
QASFLPATLT MTVDKGDNVN ISFKKVLIKE EDAVIYKNGS FIHSVPRHEV PDILEVHLPH
AQPQDAGVYS ARYIGGNLFT SAFTRLIVRR CEAQKWGPEC NHLCTACMNN GVCHEDTGEC
ICPPGFMGRT CEKACELHTF GRTCKERCSG QEGCKSYVFC LPDPYGCSCA TGWKGLQCNE
ACHPGFYGPD CKLRCSCNNG EMCDRFQGCL CSPGWQGLQC EREGIQRMTP KIVDLPDHIE
VNSGKFNPIC KASGWPLPTN EEMTLVKPDG TVLHPKDFNH TDHFSVAIFT IHRILPPDSG
VWVCSVNTVA GMVEKPFNIS VKVLPKPLNA PNVIDTGHNF AVINISSEPY FGDGPIKSKK
LLYKPVNHYE AWQHIQVTNE IVTLNYLEPR TEYELCVQLV RRGEGGEGHP GPVRRFTTAS
IGLPPPRGLN LLPKSQTTLN LTWQPIFPSS EDDFYVEVER RSVQKSDQQN IKVPGNLTSV
LLNNLHPREQ YVVRARVNTK AQGEWSEDLT AWTLSDILPP QPENIKISNI THSSAVISWT
ILDGYSISSI TIRYKVQGKN EDQHVDVKIK NATITQYQLK GLEPETAYQV DIFAENNIGS
SNPAFSHELV TLPESQAPAD LGGGKMLLIA ILGSAGMTCL TVLLAFLIIL QLKRANVQRR
MAQAFQNVRE EPAVQFNSGT LALNRKVKNN PDPTIYPVLD WNDIKFQDVI GEGNFGQVLK
ARIKKDGLRM DAAIKRMKEY ASKDDHRDFA GELEVLCKLG HHPNIINLLG ACEHRGYLYL
AIEYAPHGNL LDFLRKSRVL ETDPAFAIAN STASTLSSQQ LLHFAADVAR GMDYLSQKQF
IHRDLAARNI LVGENYVAKI ADFGLSRGQE VYVKKTMGRL PVRWMAIESL NYSVYTTNSD
VWSYGVLLWE IVSLGGTPYC GMTCAELYEK LPQGYRLEKP LNCDDEVYDL MRQCWREKPY
ERPSFAQILV SLNRMLEERK TYVNTTLYEK FTYAGIDCSA EEAA
