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Protein

Tyrosine-protein kinase receptor Tie-2

Gene

tie2

Organism
Danio rerio (Zebrafish) (Brachydanio rerio)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Tyrosine-protein kinase that acts as cell-surface receptor for angiopoietins and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Can activate or inhibit angiogenesis, depending on the context. Angiopoietin signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors (By similarity).By similarity

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-984 on the kinase activation loop.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei847 – 8471ATPPROSITE-ProRule annotation
Active sitei956 – 9561Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi822 – 8309ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: ZFIN
  • heart development Source: ZFIN
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1. 928.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine-protein kinase receptor Tie-2 (EC:2.7.10.1)
Alternative name(s):
Tyrosine kinase with Ig and EGF homology domains-2
Gene namesi
Name:tie2
Synonyms:tie-2
OrganismiDanio rerio (Zebrafish) (Brachydanio rerio)
Taxonomic identifieri7955 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiActinopterygiiNeopterygiiTeleosteiOstariophysiCypriniformesCyprinidaeDanio
Proteomesi
  • UP000000437 Componenti: Unplaced

Organism-specific databases

ZFINiZDB-GENE-990415-56. tek.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 745724ExtracellularSequence analysisAdd
BLAST
Transmembranei746 – 76621HelicalSequence analysisAdd
BLAST
Topological domaini767 – 1116350CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasm, Cytoskeleton, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 11161095Tyrosine-protein kinase receptor Tie-2PRO_0000024476Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi46 ↔ 106By similarity
Glycosylationi110 – 1101N-linked (GlcNAc...)Sequence analysis
Glycosylationi143 – 1431N-linked (GlcNAc...)Sequence analysis
Disulfide bondi215 ↔ 224By similarity
Glycosylationi223 – 2231N-linked (GlcNAc...)Sequence analysis
Disulfide bondi228 ↔ 237By similarity
Disulfide bondi231 ↔ 244By similarity
Disulfide bondi246 ↔ 255By similarity
Disulfide bondi259 ↔ 268By similarity
Disulfide bondi272 ↔ 277By similarity
Disulfide bondi283 ↔ 290By similarity
Disulfide bondi292 ↔ 301By similarity
Disulfide bondi305 ↔ 314By similarity
Disulfide bondi318 ↔ 325By similarity
Disulfide bondi320 ↔ 331By similarity
Disulfide bondi333 ↔ 341By similarity
Glycosylationi367 – 3671N-linked (GlcNAc...)Sequence analysis
Disulfide bondi368 ↔ 422By similarity
Glycosylationi387 – 3871N-linked (GlcNAc...)Sequence analysis
Glycosylationi425 – 4251N-linked (GlcNAc...)Sequence analysis
Glycosylationi590 – 5901N-linked (GlcNAc...)Sequence analysis
Glycosylationi637 – 6371N-linked (GlcNAc...)Sequence analysis
Glycosylationi642 – 6421N-linked (GlcNAc...)Sequence analysis
Modified residuei852 – 8521Phosphotyrosine; by autocatalysisBy similarity
Modified residuei984 – 9841Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1094 – 10941Phosphotyrosine; by autocatalysisBy similarity
Modified residuei1100 – 11001Phosphotyrosine; by autocatalysisBy similarity

Post-translational modificationi

Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner, where Tyr-984 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at additional tyrosine residues. Phosphorylation is important for interaction with scaffold proteins and effectors.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO73791.
PRIDEiO73791.

Expressioni

Tissue specificityi

Expressed in most populations of endothelial cells in 24 hours embryos. Not present in intersegmental vessels.1 Publication

Interactioni

Protein-protein interaction databases

STRINGi7955.ENSDARP00000055680.

Structurei

3D structure databases

ProteinModelPortaliO73791.
SMRiO73791. Positions 807-1113.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini46 – 12681Ig-like C2-type 1Add
BLAST
Domaini214 – 25643EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini258 – 30245EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini304 – 34239EGF-like 3PROSITE-ProRule annotationAdd
BLAST
Domaini348 – 43891Ig-like C2-type 2Add
BLAST
Domaini444 – 53895Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini540 – 63394Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST
Domaini634 – 72996Fibronectin type-III 3PROSITE-ProRule annotationAdd
BLAST
Domaini816 – 1095280Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily.PROSITE-ProRule annotation
Contains 3 EGF-like domains.PROSITE-ProRule annotation
Contains 3 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000049232.
HOVERGENiHBG007316.
InParanoidiO73791.
KOiK05121.
PhylomeDBiO73791.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR018941. Tyr_kin_Tie2_Ig-like_dom-1_N.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF00041. fn3. 2 hits.
PF07679. I-set. 1 hit.
PF10430. Ig_Tie2_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00181. EGF. 2 hits.
SM00060. FN3. 3 hits.
SM00409. IG. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF49265. SSF49265. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00022. EGF_1. 2 hits.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 1 hit.
PS50853. FN3. 3 hits.
PS50835. IG_LIKE. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O73791-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MCLLDSCTAL LLLGCWMSGS AVRISDVTLV NPDPVVSPLT APSLLCVSSD
60 70 80 90 100
WSSGGSVLAL GQEFPRPQGS VLALGQEFPH TEPRPHPAAA TVTWSSRSHA
110 120 130 140 150
FGAFYCQIRN STGRKIYTYK MLQEAAFLPE SLTITVNQGE NINISYSRRL
160 170 180 190 200
YSPEDTVIHK NGHFEHSSPK EDISDIIHYP VTNAKAESHA GIYAIRYISA
210 220 230 240 250
APSSAAITRL IVRSCRAGFW GPNCTESCPR CANGGVCDDT TGECVCPPGF
260 270 280 290 300
RGHTCDIVCG EGRFGAGCKE RCVDGVCRAL VFCLRDPYGC SCASGWRGLS
310 320 330 340 350
CNDACPDGYY GAGCTQKCVC AKGRCDRFRG CVCAGRHGSR CEEADSSPVI
360 370 380 390 400
SHLRDVEINT GVELSVNCSA SGRPAPLHGD ITLITANRTT IAAVDTHTLN
410 420 430 440 450
DQSTSVFRVQ QVRVSSAGRW RCQVNNTHMQ VEDEFTVEVK VPPRPQNPPV
460 470 480 490 500
LQGSGPRHLL LLLNTEPYSG DGPIATTTLL YRPASAHTWS SVTAHGPLVR
510 520 530 540 550
LDNLYPMTQY LTQVQLSRPG PGGAGQAGPA ATFSTQVLEL PVGVKLSAVS
560 570 580 590 600
QTALLLSWDI APAEQHCTYE VSCLQAGAPG TLRTFQLPSN SSAMHLSDLK
610 620 630 640 650
PRHKYQCTVR SSCGVGQNHP SASAWTLSDQ LPPPPANISI WNISDTSAVL
660 670 680 690 700
TWAVAEGESV SRAVIRFQQV EQAQYRQQVE LPVQTQQLHM RFQLLGLRPN
710 720 730 740 750
TGYQLQLWTV NNMGESAESP PVSLMTLPQQ ESSALFAAHG HLLLYAILGS
760 770 780 790 800
AGMTCCTVLL AFCIVLQLKR NTLQRRIHSI LREEPAVHFS SAPPPHRRSA
810 820 830 840 850
VVSRSLVFPA LQWSDIQFQD VLGEGNFGQV LKARIRKDGL RMDAAVKRMK
860 870 880 890 900
DYASQDDHRD FAGELEVLCR LGPHKNIIHL LGACEHRGYL YLAIEFAPHG
910 920 930 940 950
NLLDFLRKSR VLETDPAFAI AHRTASTLSS QQLLAFSADV ARGMSYLSQK
960 970 980 990 1000
QFIHRDLAAR NVLVGENFVA KIADFGLSRG QEVYVKKTMG RLPVRWMAIE
1010 1020 1030 1040 1050
SLNYSVYTTN SDVWSYGVLL WEVVSLGGTP YCGMTCAELY EKLPLGFRLE
1060 1070 1080 1090 1100
KPLNCDDEVY ELMQQCWREK PFERPSFSQI LLSLGRMLEE RKTYVNTTLY
1110
EKFTYAGIDC SAEEAG
Length:1,116
Mass (Da):122,361
Last modified:August 1, 1998 - v1
Checksum:iAA414E8C745A8937
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF053632 mRNA. Translation: AAC09331.1.
RefSeqiNP_571536.1. NM_131461.1.
UniGeneiDr.75820.

Genome annotation databases

GeneIDi30747.
KEGGidre:30747.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF053632 mRNA. Translation: AAC09331.1.
RefSeqiNP_571536.1. NM_131461.1.
UniGeneiDr.75820.

3D structure databases

ProteinModelPortaliO73791.
SMRiO73791. Positions 807-1113.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi7955.ENSDARP00000055680.

Proteomic databases

PaxDbiO73791.
PRIDEiO73791.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi30747.
KEGGidre:30747.

Organism-specific databases

CTDi7010.
ZFINiZDB-GENE-990415-56. tek.

Phylogenomic databases

eggNOGiKOG0200. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000049232.
HOVERGENiHBG007316.
InParanoidiO73791.
KOiK05121.
PhylomeDBiO73791.

Enzyme and pathway databases

BRENDAi2.7.10.1. 928.

Miscellaneous databases

PROiO73791.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR003961. FN3_dom.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR013098. Ig_I-set.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR018941. Tyr_kin_Tie2_Ig-like_dom-1_N.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF00041. fn3. 2 hits.
PF07679. I-set. 1 hit.
PF10430. Ig_Tie2_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00181. EGF. 2 hits.
SM00060. FN3. 3 hits.
SM00409. IG. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
SSF49265. SSF49265. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00022. EGF_1. 2 hits.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 1 hit.
PS50853. FN3. 3 hits.
PS50835. IG_LIKE. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Isolation of the zebrafish homologues for the tie-1 and tie-2 endothelium-specific receptor tyrosine kinases."
    Lyons M.S., Bell B., Stainier D., Peters K.G.
    Dev. Dyn. 212:133-140(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Embryo.

Entry informationi

Entry nameiTIE2_DANRE
AccessioniPrimary (citable) accession number: O73791
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: August 1, 1998
Last modified: June 8, 2016
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.