TIE2_DANRE
ID TIE2_DANRE Reviewed; 1116 AA.
AC O73791;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Tyrosine-protein kinase receptor Tie-2;
DE EC=2.7.10.1;
DE AltName: Full=Tyrosine kinase with Ig and EGF homology domains-2;
DE Flags: Precursor;
GN Name=tie2; Synonyms=tie-2;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
RX PubMed=9603430;
RX DOI=10.1002/(sici)1097-0177(199805)212:1<133::aid-aja12>3.0.co;2-8;
RA Lyons M.S., Bell B., Stainier D., Peters K.G.;
RT "Isolation of the zebrafish homologues for the tie-1 and tie-2 endothelium-
RT specific receptor tyrosine kinases.";
RL Dev. Dyn. 212:133-140(1998).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for angiopoietins and regulates angiogenesis, endothelial cell
CC survival, proliferation, migration, adhesion and cell spreading,
CC reorganization of the actin cytoskeleton, but also maintenance of
CC vascular quiescence. Can activate or inhibit angiogenesis, depending on
CC the context. Angiopoietin signaling triggers receptor dimerization and
CC autophosphorylation at specific tyrosine residues that then serve as
CC binding sites for scaffold proteins and effectors (By similarity).
CC {ECO:0000250}.
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 -!- ACTIVITY REGULATION: Angiopoietin binding leads to receptor
CC dimerization and activation by autophosphorylation at Tyr-984 on the
CC kinase activation loop. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Cell junction {ECO:0000250}. Cell
CC junction, focal adhesion {ECO:0000250}. Cytoplasm, cytoskeleton
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 (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in most populations of endothelial cells
CC in 24 hours embryos. Not present in intersegmental vessels.
CC {ECO:0000269|PubMed:9603430}.
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-984 in the
CC kinase activation loop is phosphorylated first, followed by
CC autophosphorylation at additional tyrosine residues. Phosphorylation is
CC important for interaction with scaffold proteins and effectors.
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; AF053632; AAC09331.1; -; mRNA.
DR RefSeq; NP_571536.1; NM_131461.1.
DR AlphaFoldDB; O73791; -.
DR SMR; O73791; -.
DR STRING; 7955.ENSDARP00000055680; -.
DR PaxDb; O73791; -.
DR GeneID; 30747; -.
DR KEGG; dre:30747; -.
DR CTD; 7010; -.
DR ZFIN; ZDB-GENE-990415-56; tek.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; O73791; -.
DR OrthoDB; 707342at2759; -.
DR PhylomeDB; O73791; -.
DR BRENDA; 2.7.10.1; 928.
DR Reactome; R-DRE-210993; Tie2 Signaling.
DR Reactome; R-DRE-5673001; RAF/MAP kinase cascade.
DR PRO; PR:O73791; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IMP:ZFIN.
DR GO; GO:0001935; P:endothelial cell proliferation; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; IGI:ZFIN.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IBA:GO_Central.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IBA:GO_Central.
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:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IBA:GO_Central.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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; 2.
DR Pfam; PF07679; I-set; 1.
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; SM00409; IG; 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; 2.
DR PROSITE; PS01186; EGF_2; 2.
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 2: Evidence at transcript 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; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..1116
FT /note="Tyrosine-protein kinase receptor Tie-2"
FT /id="PRO_0000024476"
FT TOPO_DOM 22..745
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 746..766
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 767..1116
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 46..126
FT /note="Ig-like C2-type 1"
FT DOMAIN 214..256
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 258..302
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 304..342
FT /note="EGF-like 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 348..438
FT /note="Ig-like C2-type 2"
FT DOMAIN 444..538
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 540..633
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 634..729
FT /note="Fibronectin type-III 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 816..1095
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 956
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 822..830
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 847
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 852
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 984
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1094
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 1100
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 223
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 590
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 642
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 46..106
FT /evidence="ECO:0000250"
FT DISULFID 215..224
FT /evidence="ECO:0000250"
FT DISULFID 228..237
FT /evidence="ECO:0000250"
FT DISULFID 231..244
FT /evidence="ECO:0000250"
FT DISULFID 246..255
FT /evidence="ECO:0000250"
FT DISULFID 259..268
FT /evidence="ECO:0000250"
FT DISULFID 272..277
FT /evidence="ECO:0000250"
FT DISULFID 283..290
FT /evidence="ECO:0000250"
FT DISULFID 292..301
FT /evidence="ECO:0000250"
FT DISULFID 305..314
FT /evidence="ECO:0000250"
FT DISULFID 318..325
FT /evidence="ECO:0000250"
FT DISULFID 320..331
FT /evidence="ECO:0000250"
FT DISULFID 333..341
FT /evidence="ECO:0000250"
FT DISULFID 368..422
FT /evidence="ECO:0000250"
SQ SEQUENCE 1116 AA; 122361 MW; AA414E8C745A8937 CRC64;
MCLLDSCTAL LLLGCWMSGS AVRISDVTLV NPDPVVSPLT APSLLCVSSD WSSGGSVLAL
GQEFPRPQGS VLALGQEFPH TEPRPHPAAA TVTWSSRSHA FGAFYCQIRN STGRKIYTYK
MLQEAAFLPE SLTITVNQGE NINISYSRRL YSPEDTVIHK NGHFEHSSPK EDISDIIHYP
VTNAKAESHA GIYAIRYISA APSSAAITRL IVRSCRAGFW GPNCTESCPR CANGGVCDDT
TGECVCPPGF RGHTCDIVCG EGRFGAGCKE RCVDGVCRAL VFCLRDPYGC SCASGWRGLS
CNDACPDGYY GAGCTQKCVC AKGRCDRFRG CVCAGRHGSR CEEADSSPVI SHLRDVEINT
GVELSVNCSA SGRPAPLHGD ITLITANRTT IAAVDTHTLN DQSTSVFRVQ QVRVSSAGRW
RCQVNNTHMQ VEDEFTVEVK VPPRPQNPPV LQGSGPRHLL LLLNTEPYSG DGPIATTTLL
YRPASAHTWS SVTAHGPLVR LDNLYPMTQY LTQVQLSRPG PGGAGQAGPA ATFSTQVLEL
PVGVKLSAVS QTALLLSWDI APAEQHCTYE VSCLQAGAPG TLRTFQLPSN SSAMHLSDLK
PRHKYQCTVR SSCGVGQNHP SASAWTLSDQ LPPPPANISI WNISDTSAVL TWAVAEGESV
SRAVIRFQQV EQAQYRQQVE LPVQTQQLHM RFQLLGLRPN TGYQLQLWTV NNMGESAESP
PVSLMTLPQQ ESSALFAAHG HLLLYAILGS AGMTCCTVLL AFCIVLQLKR NTLQRRIHSI
LREEPAVHFS SAPPPHRRSA VVSRSLVFPA LQWSDIQFQD VLGEGNFGQV LKARIRKDGL
RMDAAVKRMK DYASQDDHRD FAGELEVLCR LGPHKNIIHL LGACEHRGYL YLAIEFAPHG
NLLDFLRKSR VLETDPAFAI AHRTASTLSS QQLLAFSADV ARGMSYLSQK QFIHRDLAAR
NVLVGENFVA KIADFGLSRG QEVYVKKTMG RLPVRWMAIE SLNYSVYTTN SDVWSYGVLL
WEVVSLGGTP YCGMTCAELY EKLPLGFRLE KPLNCDDEVY ELMQQCWREK PFERPSFSQI
LLSLGRMLEE RKTYVNTTLY EKFTYAGIDC SAEEAG
