Protein detail

TIE2

Angiopoietin-1 receptor (EC 2.7.10.1) (Endothelial tyrosine kinase) (Tunica interna endothelial cell kinase) (Tyrosine kinase with Ig and EGF homology domains-2) (Tyrosine-protein kinase receptor TEK) (Tyrosine-protein kinase receptor TIE-2) (hTIE2) (p140 TEK) (CD antigen CD202b)

Entry name TIE2	UniProt ID Q02763	EVMP score 0.50
Frequency 1	Transmembrane count 1	Protein classification Cancer-related genesCD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted membrane proteinsPredicted secreted proteinsRAS pathway related proteins

EVMP score: annotation confidence score.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information

Protein Names

Protein Class

Cancer-related genesCD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted membrane proteinsPredicted secreted proteinsRAS pathway related proteins

Protein Function

ENZYME proteins:Transferases
Human disease related genes:Congenital malformations:Congenital malformations of eye
CD markers
RAS pathway related proteins
Human disease related genes:Congenital malformations:Congenital malformations of the circulatory system
Enzymes
Cancer-related genes:Candidate cancer biomarkers
Predicted secreted proteins
Kinases:Tyr protein kinases
Disease related genes
FDA approved drug targets:Small molecule drugs

Transmembrane

749..769; Helical

Transmembrane Count

Ensembl

ENSG00000120156

Entrez Gene Symbol

TEK

Gene Synonym

CD202bTIE-2TIE2VMCMVMCM1

Gene Description

TEK receptor tyrosine kinase

Chromosome

Position

27109141-27230174

Frequency

EVMP Score

0.50

Fluorescence & Localization

Tissue Specificbone marrowCell SpecificDecidual stromal cellsSingle-Nuclei Brain Specificcentral nervous system macrophage

Function & Pathway

Protein Function

ENZYME proteins:Transferases
Human disease related genes:Congenital malformations:Congenital malformations of eye
CD markers
RAS pathway related proteins
Human disease related genes:Congenital malformations:Congenital malformations of the circulatory system
Enzymes
Cancer-related genes:Candidate cancer biomarkers
Predicted secreted proteins
Kinases:Tyr protein kinases
Disease related genes
FDA approved drug targets:Small molecule drugs

Cellular Component

Molecular Function

Biological Process

KEGG

Reactome

Mediation Categories

Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation

Relations & Evidence

Enzyme-Mediated Modification

9 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
TEK	TIE1	P35590	Y	1,102	phosphorylation	Li2012
TEK	TIE1	P35590	Y	1,113	phosphorylation	Li2012
TEK	TIE1	P35590	Y	1,108	phosphorylation	Li2012
TEK	TM7SF2	O76062	Y	992	phosphorylation	REACH_ProtMapperProtMapper	ProtMapper:19451274
TEK	ANGPT1	Q15389	Y	1,102	phosphorylation	Sparser_ProtMapperProtMapper	ProtMapper:21858121
TEK	MAT1A	Q00266	Y	1,102	phosphorylation	Sparser_ProtMapperProtMapper	ProtMapper:23036162
TEK	EGFR	P00533	Y	1,048	phosphorylation	KEA	KEA:17570479
TEK	TEC	P42680	Y	1,102	phosphorylation	KEA	KEA:12082108 KEA:9632797 KEA:10521483
TEK	TEC	P42680	Y	897	phosphorylation	KEA	KEA:11513602 KEA:11080633

Ligand-Receptor Signaling

65 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
intracellular	intracellular	ComPPI	No	No	Yes	Yes	No
intracellular	intracellular	GO_Intercell	No	No	Yes	Yes	No
intracellular	intracellular	UniProt_location	No	No	Yes	Yes	No
intracellular	intracellular	OmniPath	No	No	Yes	Yes	No
adhesion	adhesion	MCAM	Yes	Yes	Yes	Yes	No
cell_adhesion	cell_adhesion	Cellinker	Yes	Yes	Yes	Yes	No
matrix_adhesion	matrix_adhesion	Zhong2015	No	Yes	Yes	Yes	No
adhesion	adhesion	OmniPath	Yes	Yes	Yes	Yes	No
cell_adhesion	cell_adhesion	OmniPath	Yes	Yes	Yes	Yes	No
matrix_adhesion	matrix_adhesion	OmniPath	No	Yes	Yes	Yes	No

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Regulatory Interaction Network

15 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
ANGP2	O15123	TIE2	Q02763	Yes	Yes	No	iTALKICELLNETSIGNORHINTSignaLink3DIPLit-BM-17HPMR_talklrCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDIntActDLRP_talklrWangRamilowski2015HPMR_LRdbCellPhoneDBHPRD_talklrCellinkerSTRING_talklrCellCallCellTalkDBFantom5_LRdbHPMR_CellinkerconnectomeDB2020LRdb	IntAct:16732286 IntAct:20708158 CellChatDB:20651738 connectomeDB2020:9723709LRdb:972CellTalkDB:9204896 HINT:15893672 HPRD:9723709 SIGNOR:9723709 Cellinker:28396397 Cellinker:9204896 Cellinker:9723709 Lit-BM-17:25237190 Lit-BM-17:9204896 DIP:15893672 IntAct:15893672 HINT:12427764 Lit-BM-17:16732286 HINT:20708158 SignaLink3:12427764 SignaLink3:18988627 Cellinker:20651738 SignaLink3:9204896 LRdb:9204896 SignaLink3:23331499 Lit-BM-17:20708158 HINT:25237190 DIP:16732286 SignaLink3:21071413 SignaLink3:9723709 Lit-BM-17:9723709 HINT:16732286 SignaLink3:15893672 HINT:9204896 HINT:9723709 connectomeDB2020:9204896 Lit-BM-17:15893672 Lit-BM-17:12427764 ICELLNET:9723709
ANGP1	Q15389	TIE2	Q02763	Yes	Yes	No	iTALKGuide2Pharma_LRdbICELLNETProtMapperSIGNORHINTSignaLink3Lit-BM-17HPMR_talklrHPMRCellChatDBHPRD_LRdbDLRP_CellinkertalklrscConnectHPRDIntActDLRP_talklrGuide2Pharma_CellinkerWangRamilowski2015HPMR_LRdbCellPhoneDBGuide2Pharma_talklrHPRD_talklrBioGRIDCellinkerREACH_ProtMapperSTRING_talklrCellCallGuide2PharmaCellTalkDBFantom5_LRdbSparser_ProtMapperHPMR_CellinkerconnectomeDB2020LRdb	SignaLink3:8980224 IntAct:20708158 CellChatDB:20651738 connectomeDB2020:9723709 HPRD:9723709 Cellinker:28396397 SIGNOR:9204896 Cellinker:9723709 Lit-BM-17:9204896 HPRD:12427764 ProtMapper:21858121 Cellinker:8980223 SignaLink3:20937382 Cellinker:8980224 connectomeDB2020:8980224 HINT:12427764 LRdb:8980224 HINT:8980223 HINT:20708158 HPRD:8980224 CellTalkDB:8980223 SignaLink3:12427764 connectomeDB2020:8980223 SignaLink3:18988627 Cellinker:20651738 SignaLink3:9204896 IntAct:29106382 LRdb:9723709 SignaLink3:23331499 Lit-BM-17:20708158 SignaLink3:8980223 SignaLink3:21071413 SignaLink3:9723709 HINT:29106382 Lit-BM-17:9723709 HINT:23592718 BioGRID:8980223 Cellinker:12427764 Lit-BM-17:8980223 HINT:9204896 LRdb:12427764 HINT:9723709 connectomeDB2020:12427764 LRdb:8980223 Lit-BM-17:12427764 ICELLNET:9723709 HPMR:8980223 HPRD:8980223
ANGP4	Q9Y264	TIE2	Q02763	Yes	Yes	No	iTALKGuide2Pharma_LRdbICELLNETSIGNORHINTSignaLink3HPRD_LRdbtalklrscConnectHPRDGuide2Pharma_CellinkerRamilowski2015CellPhoneDBGuide2Pharma_talklrHPRD_talklrCellinkerSTRING_talklrCellCallGuide2PharmaCellTalkDBFantom5_LRdbconnectomeDB2020LRdb	SignaLink3:10051567 SignaLink3:18988627 HINT:10051567 CellTalkDB:10051567 connectomeDB2020:10051567 SIGNOR:15284220 SignaLink3:15284220 SignaLink3:23331499 connectomeDB2020:15284220 ICELLNET:9723709 Cellinker:10051567 LRdb:10051567 HPRD:10051567 HINT:20708158 SignaLink3:21071413
TIE2	Q02763	TNIP2	Q8NFZ5	Yes	Yes	No	PhosphoPointHPRDSignaLink3InnateDBWangLit-BM-17	InnateDB:12609966 SignaLink3:12609966 HPRD:12609966 Lit-BM-17:12609966 SignaLink3:23331499
ANGL1	O95841	TIE2	Q02763	Yes	Yes	No	CellTalkDBDLRP_CellinkerFantom5_LRdbHPRD_LRdbKirouac2010iTALKtalklrSIGNORconnectomeDB2020HPRDHPRD_talklrSignaLink3DLRP_talklrCellinkerLRdbRamilowski2015	SignaLink3:10051567 Cellinker:10051567 CellTalkDB:10051567 SIGNOR:15284220 SignaLink3:23331499 SignaLink3:15284220 SIGNOR:10051567 LRdb:10051567 HPRD:10051567 connectomeDB2020:10051567
TIE2	Q02763	DOK2	O60496	Yes	Yes	No	PhosphoPointHPRDSignaLink3BioGRIDWang	SignaLink3:11689432 BioGRID:11689432 SignaLink3:9764820 HPRD:9764820 SignaLink3:23331499 BioGRID:9764820
TIE2	Q02763	GRAP	Q13588	Yes	Yes	No	SignaLink3	SignaLink3:23331499 SignaLink3:7478529
TIE2	Q02763	GRB7	Q14451	Yes	Yes	No	PhosphoPointHPRDSignaLink3Li2012Wang	HPRD:10521483 SignaLink3:10521483 SignaLink3:23331499
TIE2	Q02763	GRB14	Q14449	Yes	Yes	No	PhosphoPointSIGNORHPRDSignaLink3Wang	HPRD:10521483 SIGNOR:20973951 SignaLink3:20973951 SignaLink3:23331499
TIE2	Q02763	STAT1	P42224	Yes	Yes	No	SIGNORSparser_ProtMapperProtMapper	SIGNOR:18401423 ProtMapper:18401423

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Protein Complex Composition

15 records.

Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs
ANGPT2 TEK	O15123 Q02763	1:1	PDB	PDB:2gy7
ANGPT1 ANGPT2 TEK	O15123 Q02763 Q15389	1:1:1	CompleatCFinder	Compleat:HC4051
CRY1 CRY2 PER1 TEKT4	O15534 Q16526 Q49AN0 Q8WW24	0:0:0:0	hu.MAP2
CRY1 CRY2 FBXL3 PER1 TEKT4	O15534 Q16526 Q49AN0 Q8WW24 Q9UKT7	0:0:0:0:0	hu.MAP2
CRY2 PER3 TEKT4	P56645 Q49AN0 Q8WW24	0:0:0	hu.MAP
TEK	Q02763	2	PDB	PDB:5myaPDB:7e72PDB:2p4iPDB:6mwePDB:5mybPDB:5utkPDB:1fvr
ANGPT1 TEK	Q02763 Q15389	1:1	PDB	PDB:4k0v
CRY1 CRY2 FBXL3 TEKT4	Q16526 Q49AN0 Q8WW24 Q9UKT7	0:0:0:0	hu.MAP2
CRY1 TEKT4	Q16526 Q8WW24	0:0	hu.MAP
CRY2 TEKT4	Q49AN0 Q8WW24	0:0	hu.MAP

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Isolation & Detection Technology

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential Ultracentrifugation	Mass spectrometry	1	24700864

Sequence, Structure & Domains

Sequences

Length

1,124

Mass

125,830

Sequence

MDSLASLVLCGVSLLLSGTVEGAMDLILINSLPLVSDAETSLTCIASGWRPHEPITIGRDFEALMNQHQDPLEVTQDVTREWAKKVVWKREKASKINGAYFCEGRVRGEAIRIRTMKMRQQASFLPATLTMTVDKGDNVNISFKKVLIKEEDAVIYKNGSFIHSVPRHEVPDILEVHLPHAQPQDAGVYSARYIGGNLFTSAFTRLIVRRCEAQKWGPECNHLCTACMNNGVCHEDTGECICPPGFMGRTCEKACELHTFGRTCKERCSGQEGCKSYVFCLPDPYGCSCATGWKGLQCNEACHPGFYGPDCKLRCSCNNGEMCDRFQGCLCSPGWQGLQCEREGIQRMTPKIVDLPDHIEVNSGKFNPICKASGWPLPTNEEMTLVKPDGTVLHPKDFNHTDHFSVAIFTIHRILPPDSGVWVCSVNTVAGMVEKPFNISVKVLPKPLNAPNVIDTGHNFAVINISSEPYFGDGPIKSKKLLYKPVNHYEAWQHIQVTNEIVTLNYLEPRTEYELCVQLVRRGEGGEGHPGPVRRFTTASIGLPPPRGLNLLPKSQTTLNLTWQPIFPSSEDDFYVEVERRSVQKSDQQNIKVPGNLTSVLLNNLHPREQYVVRARVNTKAQGEWSEDLTAWTLSDILPPQPENIKISNITHSSAVISWTILDGYSISSITIRYKVQGKNEDQHVDVKIKNATITQYQLKGLEPETAYQVDIFAENNIGSSNPAFSHELVTLPESQAPADLGGGKMLLIAILGSAGMTCLTVLLAFLIILQLKRANVQRRMAQAFQNVREEPAVQFNSGTLALNRKVKNNPDPTIYPVLDWNDIKFQDVIGEGNFGQVLKARIKKDGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLRKSRVLETDPAFAIANSTASTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRGQEVYVKKTMGRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLEERKTYVNTTLYEKFTYAGIDCSAEEAA

Alternative Products

Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q02763-1; Sequence=Displayed; Name=2; IsoId=Q02763-2; Sequence=VSP_042138; Name=3; IsoId=Q02763-3; Sequence=VSP_042137, VSP_042138, VSP_042139

Alternative Sequence

18..121; Missing (in isoform 3); 300..342; Missing (in isoform 2 and isoform 3); 788; Missing (in isoform 3)

3D Structural Models

Turn

61..63; 235..237; 271..276; 282..285; 325..327; 1038..1041

Helix

167..169; 183..185; 198..200; 296..298; 380..382; 416..418; 821..823; 864..866; 872..879; 910..916; 919..922; 924..929; 938..957; 967..969; 974..976; 985..987; 1000..1004; 1007..1012; 1017..1032; 1044..1050; 1051..1053; 1065..1074; 1079..1081; 1085..1097; 1118..1120

Beta Strand

26..29; 33..35; 40..46; 56..59; 64..66; 74..76; 80..88; 98..106; 109..119; 123..125; 127..133; 139..145; 153..157; 160..165; 172..178; 187..193; 202..208; 215..217; 246..248; 259..261; 279..281; 286..288; 322..324; 328..330; 361..366; 369..373; 383..386; 396..400; 405..408; 411..414; 420..428; 431..439; 446..449; 452..456; 461..464; 469..472; 476..485; 493..504; 512..521; 534..537; 550..555; 558..562; 569..572; 575..585; 588..594; 598..602; 610..621; 629..632; 643..648; 655..660; 663..665; 669..677; 683..689; 696..699; 707..715; 727..730; 816..818; 824..833; 836..845; 848..857; 888..894; 897..903; 932..936; 970..972; 978..980; 1098..1100

3D Structure

X-ray crystallography (16)

Domain & Motif Annotations

Domain (CC)

The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins.

Domain (FT)

44..123; Ig-like C2-type 1; 210..252; EGF-like 1; 254..299; EGF-like 2; 301..341; EGF-like 3; 350..440; Ig-like C2-type 2; 447..541; Fibronectin type-III 1; 545..636; Fibronectin type-III 2; 641..735; Fibronectin type-III 3; 824..1096; Protein kinase

Protein Families

Protein kinase superfamily
Tyr protein kinase family
Tie subfamily

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily.

Clinical Relevance

Disease Involvement

Cancer-related genesDisease variantFDA approved drug targetsGlaucoma

Related Diseases

Breast cancer Chronic arterial occlusive disease Ischemia Mature B-cell lymphoma Myelodysplastic syndrome Myeloproliferative neoplasm Retinopathy Rheumatoid arthritis Sepsis Solid tumour/cancer

Biomarker

Phase 1; Phase 2; Investigative; Discontinued in Phase 1; Phase 1/2

Drug Targets

FDA approved drug targets

Drugs

FORETINIB REBASTINIB GLESATINIB REGORAFENIB RAZUPROTAFIB CETIRIZINE HYDROCHLORIDE ALTIRATINIB CE-245677 LINIFANIB CEP-11981 GW559768X PEXMETINIB VANDETANIB CABOZANTINIB S-MALATE LOPERAMIDE AMPICILLIN (ANHYDROUS)

Antibody

CAB010359 HPA073265

Interaction Protein

ENSG00000091879ENSG00000154188

Interaction Count

Interaction Dataset

intact_biogrid