TIE2_MOUSE
ID TIE2_MOUSE Reviewed; 1122 AA.
AC Q02858;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Angiopoietin-1 receptor;
DE EC=2.7.10.1;
DE AltName: Full=Endothelial tyrosine kinase;
DE AltName: Full=HYK;
DE AltName: Full=STK1;
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=mTIE2;
DE AltName: Full=p140 TEK;
DE AltName: CD_antigen=CD202b;
DE Flags: Precursor;
GN Name=Tek; Synonyms=Hyk, Tie-2, Tie2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Lung;
RX PubMed=8415706; DOI=10.1073/pnas.90.20.9355;
RA Sato T.N., Qin Y., Kozak C.A., Andus K.L.;
RT "Tie-1 and tie-2 define another class of putative receptor tyrosine kinase
RT genes expressed in early embryonic vascular system.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:9355-9358(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CD-1; TISSUE=Embryonic heart;
RX PubMed=8386827;
RA Dumont D.J., Gradwol G.J., Fong G.-H., Auerbach R., Breitman M.L.;
RT "The endothelial-specific receptor tyrosine kinase, tek, is a member of a
RT new subfamily of receptors.";
RL Oncogene 8:1293-1301(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryonic stem cell;
RX PubMed=1282811; DOI=10.1016/0006-291x(92)90280-x;
RA Horita K., Yagi T., Kohmura N., Tomooka Y., Ikawa Y., Aizawa S.;
RT "A novel tyrosine kinase, hyk, expressed in murine embryonic stem cells.";
RL Biochem. Biophys. Res. Commun. 189:1747-1753(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=8217221;
RA Runting A.S., Stacker S.A., Wilks A.F.;
RT "Tie2, a putative protein tyrosine kinase from a new class of cell surface
RT receptor.";
RL Growth Factors 9:99-105(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8187650; DOI=10.1242/dev.119.3.957;
RA Schnuerch H., Risau W.;
RT "Expression of tie-2, a member of a novel family of receptor tyrosine
RT kinases, in the endothelial cell lineage.";
RL Development 119:957-968(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Hematopoietic stem cell;
RX PubMed=8395828; DOI=10.1006/bbrc.1993.2045;
RA Iwama A., Hamaguchi I., Hashiyama M., Murayama Y., Yasunaga K., Suda T.;
RT "Molecular cloning and characterization of mouse TIE and TEK receptor
RT tyrosine kinase genes and their expression in hematopoietic stem cells.";
RL Biochem. Biophys. Res. Commun. 195:301-309(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 822-1122.
RC STRAIN=CD-1; TISSUE=Embryonic heart;
RX PubMed=1630810;
RA Dumont D.J., Yamaguchi T.P., Conlon R.A., Rossant J., Breitman M.L.;
RT "Tek, a novel tyrosine kinase gene located on mouse chromosome 4, is
RT expressed in endothelial cells and their presumptive precursors.";
RL Oncogene 7:1471-1480(1992).
RN [8]
RP DISRUPTION PHENOTYPE, MUTAGENESIS OF LYS-853, CATALYTIC ACTIVITY, AND
RP FUNCTION.
RX PubMed=7958865; DOI=10.1101/gad.8.16.1897;
RA Dumont D.J., Gradwohl G., Fong G.H., Puri M.C., Gertsenstein M.,
RA Auerbach A., Breitman M.L.;
RT "Dominant-negative and targeted null mutations in the endothelial receptor
RT tyrosine kinase, tek, reveal a critical role in vasculogenesis of the
RT embryo.";
RL Genes Dev. 8:1897-1909(1994).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=7596437; DOI=10.1038/376070a0;
RA Sato T.N., Tozawa Y., Deutsch U., Wolburg-Buchholz K., Fujiwara Y.,
RA Gendron-Maguire M., Gridley T., Wolburg H., Risau W., Qin Y.;
RT "Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood
RT vessel formation.";
RL Nature 376:70-74(1995).
RN [10]
RP INTERACTION WITH PIK3R1, MUTAGENESIS OF TYR-1100, AND FUNCTION IN
RP ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE AND AKT1.
RX PubMed=9632797; DOI=10.1128/mcb.18.7.4131;
RA Kontos C.D., Stauffer T.P., Yang W.P., York J.D., Huang L., Blanar M.A.,
RA Meyer T., Peters K.G.;
RT "Tyrosine 1101 of Tie2 is the major site of association of p85 and is
RT required for activation of phosphatidylinositol 3-kinase and Akt.";
RL Mol. Cell. Biol. 18:4131-4140(1998).
RN [11]
RP INTERACTION WITH GRB2; GRB7, GRB14, PTPN11/SHP2 AND PIK3R1, FUNCTION IN
RP PHOSPHORYLATION OF GRB7 AND PIK3R1, AND MUTAGENESIS OF TYR-1100.
RX PubMed=10521483; DOI=10.1074/jbc.274.43.30896;
RA Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R.,
RA Alitalo K., Dumont D.J.;
RT "Identification of Tek/Tie2 binding partners. Binding to a multifunctional
RT docking site mediates cell survival and migration.";
RL J. Biol. Chem. 274:30896-30905(1999).
RN [12]
RP PHOSPHORYLATION, AND DEPHOSPHORYLATION BY PTPRB.
RX PubMed=10557082; DOI=10.1038/sj.onc.1202992;
RA Fachinger G., Deutsch U., Risau W.;
RT "Functional interaction of vascular endothelial-protein-tyrosine
RT phosphatase with the angiopoietin receptor Tie-2.";
RL Oncogene 18:5948-5953(1999).
RN [13]
RP ANTI-APOPTOTIC FUNCTION.
RX PubMed=11375937; DOI=10.1093/embo-reports/kve093;
RA Jones N., Voskas D., Master Z., Sarao R., Jones J., Dumont D.J.;
RT "Rescue of the early vascular defects in Tek/Tie2 null mice reveals an
RT essential survival function.";
RL EMBO Rep. 2:438-445(2001).
RN [14]
RP INTERACTION WITH ANGPT1 AND ANGPT2, AND DOMAIN.
RX PubMed=12427764; DOI=10.1074/jbc.m208550200;
RA Fiedler U., Krissl T., Koidl S., Weiss C., Koblizek T., Deutsch U.,
RA Martiny-Baron G., Marme D., Augustin H.G.;
RT "Angiopoietin-1 and angiopoietin-2 share the same binding domains in the
RT Tie-2 receptor involving the first Ig-like loop and the epidermal growth
RT factor-like repeats.";
RL J. Biol. Chem. 278:1721-1727(2003).
RN [15]
RP PHOSPHORYLATION AT TYR-1100 AND TYR-1106, MUTAGENESIS OF LYS-853; TYR-1100
RP AND TYR-1106, FUNCTION IN DOK2 PHOSPHORYLATION, AND INTERACTION WITH DOK2.
RX PubMed=12665569; DOI=10.1128/mcb.23.8.2658-2668.2003;
RA Jones N., Chen S.H., Sturk C., Master Z., Tran J., Kerbel R.S.,
RA Dumont D.J.;
RT "A unique autophosphorylation site on Tie2/Tek mediates Dok-R
RT phosphotyrosine binding domain binding and function.";
RL Mol. Cell. Biol. 23:2658-2668(2003).
RN [16]
RP FUNCTION AS ANGPT4 RECEPTOR AND IN ACTIVATION OF AKT1, INTERACTION WITH
RP ANGPT4, AND AUTOPHOSPHORYLATION.
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 [17]
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [19]
RP INTERACTION WITH GRB14, AND FUNCTION IN GRB14 PHOSPHORYLATION.
RX PubMed=20973951; DOI=10.1186/1478-811x-8-30;
RA Sturk C., Dumont D.J.;
RT "Tyrosine phosphorylation of Grb14 by Tie2.";
RL Cell Commun. Signal. 8:30-30(2010).
RN [20]
RP DISRUPTION PHENOTYPE.
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:10521483, ECO:0000269|PubMed:12665569,
CC ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:20973951,
CC ECO:0000269|PubMed:7596437, ECO:0000269|PubMed:7958865,
CC ECO:0000269|PubMed:9632797}.
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:7958865};
CC -!- ACTIVITY REGULATION: Angiopoietin binding leads to receptor
CC dimerization and activation by autophosphorylation at Tyr-990 on the
CC kinase activation loop. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Heterodimer with TIE1. Interacts with ANGPT1,
CC ANGPT2 and ANGPT4. At cell-cell contacts in quiescent cells, forms a
CC signaling complex composed of ANGPT1 plus TEK molecules from two
CC adjoining cells. In the absence of endothelial cell-cell contacts,
CC interaction with ANGPT1 mediates contacts with the extracellular
CC matrix. Interacts (tyrosine phosphorylated) with TNIP2. Interacts
CC (tyrosine phosphorylated) with SHC1 (via SH2 domain) (By similarity).
CC Interacts with PTPRB; this promotes endothelial cell-cell adhesion.
CC Interacts with DOK2, GRB2, GRB7, GRB14, PIK3R1 and PTPN11/SHP2.
CC Colocalizes with DOK2 at contacts with the extracellular matrix in
CC migrating cells. {ECO:0000250, ECO:0000269|PubMed:10521483,
CC ECO:0000269|PubMed:12427764, ECO:0000269|PubMed:12665569,
CC ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:19451274,
CC ECO:0000269|PubMed:20973951, ECO:0000269|PubMed:9632797}.
CC -!- INTERACTION:
CC Q02858; Q60631: Grb2; NbExp=3; IntAct=EBI-7099626, EBI-1688;
CC Q02858; Q03160: Grb7; NbExp=3; IntAct=EBI-7099626, EBI-7100053;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Cell junction {ECO:0000250}. Cell junction, focal adhesion
CC {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Secreted
CC {ECO:0000250}. Note=Recruited to cell-cell contacts in quiescent
CC endothelial cells. Colocalizes with the actin cytoskeleton and at actin
CC stress fibers during cell spreading. Recruited to the lower surface of
CC migrating cells, especially the rear end of the cell. Proteolytic
CC processing gives rise to a soluble extracellular domain that is
CC secreted (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in developing vascular
CC endothelial cells. Abundantly expressed in lung and heart, moderately
CC in brain, liver and kidney, and weakly in thymus, spleen and testis.
CC {ECO:0000269|PubMed:8395828}.
CC -!- DEVELOPMENTAL STAGE: Expression detectable in day 8.5 embryos.
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. {ECO:0000250}.
CC -!- PTM: Proteolytic processing leads to the shedding of the extracellular
CC domain (soluble TIE-2 alias sTIE-2). {ECO:0000250}.
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-990 in the
CC kinase activation loop is phosphorylated first, followed by
CC autophosphorylation at Tyr-1106 and at additional tyrosine residues.
CC ANGPT1-induced phosphorylation is impaired during hypoxia, due to
CC increased expression of ANGPT2 (By similarity). Phosphorylation is
CC important for interaction with GRB14, PIK3R1 and PTPN11.
CC Phosphorylation at Tyr-1100 is important for interaction with GRB2 and
CC GRB7. Phosphorylation at Tyr-1106 is important for interaction with
CC DOK2 and for coupling to downstream signal transduction pathways in
CC endothelial cells. Dephosphorylated by PTPRB. {ECO:0000250,
CC ECO:0000269|PubMed:10557082, ECO:0000269|PubMed:12665569}.
CC -!- PTM: Ubiquitinated. The phosphorylated receptor is ubiquitinated and
CC internalized, leading to its degradation (By similarity).
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Embryonically lethal. Embryos die at about 10
CC dpc, due to strongly decreased numbers of blood vessel endothelial
CC cells, leading to severe hemorrhaging, and due to defects in heart
CC trabeculae development. Mice display a general malformation of the
CC vascular network with defective sprouting and dilated blood vessels.
CC Conditional by inversion allele knockout mice don't have Schlemm's
CC canal. Haploinsufficient mice developed a severely hypomorphic
CC Schlemm's canal with convolutions and focal narrowing
CC (PubMed:27270174). {ECO:0000269|PubMed:27270174,
CC ECO:0000269|PubMed:7596437, ECO:0000269|PubMed:7958865}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Tie subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; X71426; CAA50557.1; -; mRNA.
DR EMBL; X67553; CAA47857.1; -; mRNA.
DR EMBL; D13738; BAA02883.1; -; mRNA.
DR EMBL; S67051; AAB28663.1; -; mRNA.
DR CCDS; CCDS71421.1; -.
DR PIR; I54237; I54237.
DR PIR; JH0771; JH0771.
DR PIR; JN0712; JN0712.
DR RefSeq; NP_001277478.1; NM_001290549.1.
DR AlphaFoldDB; Q02858; -.
DR SMR; Q02858; -.
DR BioGRID; 204107; 5.
DR IntAct; Q02858; 6.
DR MINT; Q02858; -.
DR STRING; 10090.ENSMUSP00000099862; -.
DR BindingDB; Q02858; -.
DR ChEMBL; CHEMBL5199; -.
DR DrugCentral; Q02858; -.
DR GlyConnect; 2128; 1 N-Linked glycan (1 site).
DR GlyGen; Q02858; 9 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q02858; -.
DR PhosphoSitePlus; Q02858; -.
DR CPTAC; non-CPTAC-3433; -.
DR jPOST; Q02858; -.
DR MaxQB; Q02858; -.
DR PaxDb; Q02858; -.
DR PRIDE; Q02858; -.
DR ProteomicsDB; 259026; -.
DR Antibodypedia; 2050; 1376 antibodies from 44 providers.
DR DNASU; 21687; -.
DR Ensembl; ENSMUST00000071168; ENSMUSP00000071162; ENSMUSG00000006386.
DR GeneID; 21687; -.
DR KEGG; mmu:21687; -.
DR UCSC; uc008tsk.2; mouse.
DR CTD; 7010; -.
DR MGI; MGI:98664; Tek.
DR VEuPathDB; HostDB:ENSMUSG00000006386; -.
DR eggNOG; KOG0200; Eukaryota.
DR GeneTree; ENSGT00940000158840; -.
DR InParanoid; Q02858; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 21687; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q02858; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q02858; protein.
DR Bgee; ENSMUSG00000006386; Expressed in vasculature of brain and 292 other tissues.
DR ExpressionAtlas; Q02858; baseline and differential.
DR Genevisible; Q02858; MM.
DR GO; GO:0005884; C:actin filament; ISO:MGI.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR GO; GO:0034451; C:centriolar satellite; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISM:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0001725; C:stress fiber; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019838; F:growth factor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IPI:MGI.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; TAS:DFLAT.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:MGI.
DR GO; GO:0007160; P:cell-matrix adhesion; IMP:MGI.
DR GO; GO:0001935; P:endothelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0072012; P:glomerulus vasculature development; ISO:MGI.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0060347; P:heart trabecula formation; IMP:UniProtKB.
DR GO; GO:0030097; P:hemopoiesis; IMP:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IGI:MGI.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:MGI.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IDA:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISS:UniProtKB.
DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISS: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:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:MGI.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; TAS:DFLAT.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; IMP:MGI.
DR GO; GO:0030334; P:regulation of cell migration; IDA:MGI.
DR GO; GO:0001936; P:regulation of endothelial cell proliferation; TAS:DFLAT.
DR GO; GO:0032878; P:regulation of establishment or maintenance of cell polarity; ISS:UniProtKB.
DR GO; GO:1901222; P:regulation of NIK/NF-kappaB signaling; IGI:MGI.
DR GO; GO:0043627; P:response to estrogen; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR GO; GO:0032526; P:response to retinoic acid; IDA:BHF-UCL.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISS:UniProtKB.
DR GO; GO:0048014; P:Tie signaling pathway; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; ISS:UniProtKB.
DR GO; GO:0001570; P:vasculogenesis; IMP:UniProtKB.
DR CDD; cd00055; EGF_Lam; 1.
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; 2.
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 ATP-binding; Cell junction; Cell membrane; Cytoplasm; Cytoskeleton;
KW Disulfide bond; EGF-like domain; Glycoprotein; Immunoglobulin domain;
KW Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..22
FT /evidence="ECO:0000250"
FT CHAIN 23..1122
FT /note="Angiopoietin-1 receptor"
FT /id="PRO_0000024475"
FT TOPO_DOM 23..746
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 747..767
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 768..1122
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 444..539
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 543..635
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 640..733
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 822..1094
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 962
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 828..836
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 853
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 858
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q02763"
FT MOD_RES 990
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q02763"
FT MOD_RES 1100
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:12665569"
FT MOD_RES 1106
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12665569"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 558
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 595
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 648
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 690
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 44..102
FT /evidence="ECO:0000250"
FT DISULFID 211..220
FT /evidence="ECO:0000250"
FT DISULFID 224..233
FT /evidence="ECO:0000250"
FT DISULFID 227..240
FT /evidence="ECO:0000250"
FT DISULFID 242..251
FT /evidence="ECO:0000250"
FT DISULFID 255..264
FT /evidence="ECO:0000250"
FT DISULFID 268..274
FT /evidence="ECO:0000250"
FT DISULFID 280..287
FT /evidence="ECO:0000250"
FT DISULFID 289..298
FT /evidence="ECO:0000250"
FT DISULFID 302..311
FT /evidence="ECO:0000250"
FT DISULFID 315..323
FT /evidence="ECO:0000250"
FT DISULFID 317..329
FT /evidence="ECO:0000250"
FT DISULFID 331..340
FT /evidence="ECO:0000250"
FT DISULFID 370..424
FT /evidence="ECO:0000250"
FT MUTAGEN 853
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12665569,
FT ECO:0000269|PubMed:7958865"
FT MUTAGEN 1100
FT /note="Y->F: Reduced levels of autophosphorylation.
FT Abolishes interaction with GRB2 and GRB7. Abolishes
FT phosphorylation of GRB7 and PIK3R1."
FT /evidence="ECO:0000269|PubMed:10521483,
FT ECO:0000269|PubMed:12665569, ECO:0000269|PubMed:9632797"
FT MUTAGEN 1106
FT /note="Y->F: Reduced levels of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:12665569"
FT CONFLICT 161..171
FT /note="FIHSVPRHEVP -> LHPLSAPGMKYL (in Ref. 3; BAA02883)"
FT /evidence="ECO:0000305"
FT CONFLICT 538
FT /note="S -> C (in Ref. 2; CAA47857)"
FT /evidence="ECO:0000305"
FT CONFLICT 736
FT /note="A -> G (in Ref. 2; CAA47857 and 4; AAB28663)"
FT /evidence="ECO:0000305"
FT CONFLICT 745..761
FT /note="MLLIAILGSAGMTCITV -> DATHSHPWVWNDFASPC (in Ref. 3;
FT BAA02883)"
FT /evidence="ECO:0000305"
FT CONFLICT 786
FT /note="N -> NV (in Ref. 3; BAA02883 and 6; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 913
FT /note="R -> G (in Ref. 3; BAA02883)"
FT /evidence="ECO:0000305"
FT CONFLICT 925..931
FT /note="AIANSTA -> CHRQQYS (in Ref. 3; BAA02883)"
FT /evidence="ECO:0000305"
FT CONFLICT 1117
FT /note="S -> P (in Ref. 3; BAA02883)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1122 AA; 125701 MW; F879623D103FFE96 CRC64;
MDSLAGLVLC GVSLLLYGVV EGAMDLILIN SLPLVSDAET SLTCIASGWH PHEPITIGRD
FEALMNQHQD PLEVTQDVTR EWAKKVVWKR EKASKINGAY FCEGRVRGQA IRIRTMKMRQ
QASFLPATLT MTVDRGDNVN ISFKKVLIKE EDAVIYKNGS FIHSVPRHEV PDILEVHLPH
AQPQDAGVYS ARYIGGNLFT SAFTRLIVRR CEAQKWGPDC SRPCTTCKNN GVCHEDTGEC
ICPPGFMGRT CEKACEPHTF GRTCKERCSG PEGCKSYVFC LPDPYGCSCA TGWRGLQCNE
ACPSGYYGPD CKLRCHCTNE EICDRFQGCL CSQGWQGLQC EKEGRPRMTP QIEDLPDHIE
VNSGKFNPIC KASGWPLPTS EEMTLVKPDG TVLQPNDFNY TDRFSVAIFT VNRVLPPDSG
VWVCSVNTVA GMVEKPFNIS VKVLPEPLHA PNVIDTGHNF AIINISSEPY FGDGPIKSKK
LFYKPVNQAW KYIEVTNEIF TLNYLEPRTD YELCVQLARP GEGGEGHPGP VRRFTTASIG
LPPPRGLSLL PKSQTALNLT WQPIFTNSED EFYVEVERRS LQTTSDQQNI KVPGNLTSVL
LSNLVPREQY TVRARVNTKA QGEWSEELRA WTLSDILPPQ PENIKISNIT DSTAMVSWTI
VDGYSISSII IRYKVQGKNE DQHIDVKIKN ATVTQYQLKG LEPETTYHVD IFAENNIGSS
NPAFSHELRT LPHSPASADL GGGKMLLIAI LGSAGMTCIT VLLAFLIMLQ LKRANVQRRM
AQAFQNREEP AVQFNSGTLA LNRKAKNNPD PTIYPVLDWN DIKFQDVIGE GNFGQVLKAR
IKKDGLRMDA AIKRMKEYAS KDDHRDFAGE LEVLCKLGHH PNIINLLGAC EHRGYLYLAI
EYAPHGNLLD FLRKSRVLET DPAFAIANST ASTLSSQQLL HFAADVARGM DYLSQKQFIH
RDLAARNILV GENYIAKIAD FGLSRGQEVY VKKTMGRLPV RWMAIESLNY SVYTTNSDVW
SYGVLLWEIV SLGGTPYCGM TCAELYEKLP QGYRLEKPLN CDDEVYDLMR QCWREKPYER
PSFAQILVSL NRMLEERKTY VNTTLYEKFT YAGIDCSAEE AA
