GenomeNet

Database: UniProt
Entry: O73791
LinkDB: O73791
Original site: O73791 
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   16-JAN-2019, entry version 141.
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   Cyprinidae; 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
RT   endothelium-specific receptor tyrosine kinases.";
RL   Dev. Dyn. 212:133-140(1998).
CC   -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface
CC       receptor for angiopoietins and regulates angiogenesis, endothelial
CC       cell survival, proliferation, migration, adhesion and cell
CC       spreading, reorganization of the actin cytoskeleton, but also
CC       maintenance of vascular quiescence. Can activate or inhibit
CC       angiogenesis, depending on the context. Angiopoietin signaling
CC       triggers receptor dimerization and autophosphorylation at specific
CC       tyrosine residues that then serve as binding sites for scaffold
CC       proteins and effectors (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-
CC         tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136,
CC         Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216;
CC         EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC   -!- ACTIVITY REGULATION: Angiopoietin binding leads to receptor
CC       dimerization and activation by autophosphorylation at Tyr-984 on
CC       the kinase activation loop. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass
CC       type I membrane protein {ECO:0000250}. Cell junction
CC       {ECO:0000250}. Cell junction, focal adhesion {ECO:0000250}.
CC       Cytoplasm, cytoskeleton {ECO:0000250}. Note=Recruited to cell-cell
CC       contacts in quiescent endothelial cells. Colocalizes with the
CC       actin cytoskeleton and at actin stress fibers during cell
CC       spreading. Recruited to the lower surface of migrating cells,
CC       especially the rear end of the cell (By similarity).
CC       {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed in most populations of endothelial
CC       cells 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
CC       the dimeric receptor phosphorylates tyrosine residues on the other
CC       subunit. Autophosphorylation occurs in a sequential manner, where
CC       Tyr-984 in the kinase activation loop is phosphorylated first,
CC       followed by autophosphorylation at additional tyrosine residues.
CC       Phosphorylation is important for interaction with scaffold
CC       proteins and effectors.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. Tie subfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00159}.
DR   EMBL; AF053632; AAC09331.1; -; mRNA.
DR   RefSeq; NP_571536.1; NM_131461.1.
DR   UniGene; Dr.75820; -.
DR   ProteinModelPortal; O73791; -.
DR   SMR; O73791; -.
DR   STRING; 7955.ENSDARP00000055680; -.
DR   PaxDb; O73791; -.
DR   PRIDE; O73791; -.
DR   GeneID; 30747; -.
DR   KEGG; dre:30747; -.
DR   CTD; 7010; -.
DR   ZFIN; ZDB-GENE-990415-56; tek.
DR   eggNOG; KOG0200; Eukaryota.
DR   eggNOG; COG0515; LUCA.
DR   HOGENOM; HOG000049232; -.
DR   HOVERGEN; HBG007316; -.
DR   InParanoid; O73791; -.
DR   KO; K05121; -.
DR   OrthoDB; 707342at2759; -.
DR   PhylomeDB; O73791; -.
DR   BRENDA; 2.7.10.1; 928.
DR   PRO; PR:O73791; -.
DR   Proteomes; UP000000437; 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: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; IPR013032; EGF-like_CS.
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; Pkinase_Tyr; 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; Complete proteome;
KW   Cytoplasm; Cytoskeleton; Disulfide bond; EGF-like domain;
KW   Glycoprotein; Immunoglobulin domain; Kinase; Membrane;
KW   Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW   Repeat; Signal; Transferase; Transmembrane; Transmembrane helix;
KW   Tyrosine-protein kinase.
FT   SIGNAL        1     21       {ECO:0000255}.
FT   CHAIN        22   1116       Tyrosine-protein kinase receptor Tie-2.
FT                                /FTId=PRO_0000024476.
FT   TOPO_DOM     22    745       Extracellular. {ECO:0000255}.
FT   TRANSMEM    746    766       Helical. {ECO:0000255}.
FT   TOPO_DOM    767   1116       Cytoplasmic. {ECO:0000255}.
FT   DOMAIN       46    126       Ig-like C2-type 1.
FT   DOMAIN      214    256       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      258    302       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      304    342       EGF-like 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      348    438       Ig-like C2-type 2.
FT   DOMAIN      444    538       Fibronectin type-III 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00316}.
FT   DOMAIN      540    633       Fibronectin type-III 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00316}.
FT   DOMAIN      634    729       Fibronectin type-III 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00316}.
FT   DOMAIN      816   1095       Protein kinase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   NP_BIND     822    830       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   ACT_SITE    956    956       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159, ECO:0000255|PROSITE-
FT                                ProRule:PRU10028}.
FT   BINDING     847    847       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   MOD_RES     852    852       Phosphotyrosine; by autocatalysis.
FT                                {ECO:0000250}.
FT   MOD_RES     984    984       Phosphotyrosine; by autocatalysis.
FT                                {ECO:0000250}.
FT   MOD_RES    1094   1094       Phosphotyrosine; by autocatalysis.
FT                                {ECO:0000250}.
FT   MOD_RES    1100   1100       Phosphotyrosine; by autocatalysis.
FT                                {ECO:0000250}.
FT   CARBOHYD    110    110       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    143    143       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    223    223       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    367    367       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    387    387       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    425    425       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    590    590       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    637    637       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    642    642       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     46    106       {ECO:0000250}.
FT   DISULFID    215    224       {ECO:0000250}.
FT   DISULFID    228    237       {ECO:0000250}.
FT   DISULFID    231    244       {ECO:0000250}.
FT   DISULFID    246    255       {ECO:0000250}.
FT   DISULFID    259    268       {ECO:0000250}.
FT   DISULFID    272    277       {ECO:0000250}.
FT   DISULFID    283    290       {ECO:0000250}.
FT   DISULFID    292    301       {ECO:0000250}.
FT   DISULFID    305    314       {ECO:0000250}.
FT   DISULFID    318    325       {ECO:0000250}.
FT   DISULFID    320    331       {ECO:0000250}.
FT   DISULFID    333    341       {ECO:0000250}.
FT   DISULFID    368    422       {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
//
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