TIE1

Protein identityUniProt · HPA

UniProt accession

P35590

Gene

TIE1

Ensembl

ENSG00000066056

Chromosome

1

Canonical length

1138 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes a member of the tyrosine protein kinase family. The encoded protein plays a critical role in angiogenesis and blood vessel stability by inhibiting angiopoietin 1 signaling through the endothelial receptor tyrosine kinase Tie2. Ectodomain cleavage of the encoded protein relieves inhibition of Tie2 and is mediated by multiple factors including vascular endothelial growth factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Canonical amino-acid sequenceUniProt

1138 residues, UniProt reviewed canonical sequence.

>P35590|TIE1
     1  MVWRVPPFLL PILFLASHVG AAVDLTLLAN LRLTDPQRFF LTCVSGEAGA GRGSDAWGPP
    61  LLLEKDDRIV RTPPGPPLRL ARNGSHQVTL RGFSKPSDLV GVFSCVGGAG ARRTRVIYVH
   121  NSPGAHLLPD KVTHTVNKGD TAVLSARVHK EKQTDVIWKS NGSYFYTLDW HEAQDGRFLL
   181  QLPNVQPPSS GIYSATYLEA SPLGSAFFRL IVRGCGAGRW GPGCTKECPG CLHGGVCHDH
   241  DGECVCPPGF TGTRCEQACR EGRFGQSCQE QCPGISGCRG LTFCLPDPYG CSCGSGWRGS
   301  QCQEACAPGH FGADCRLQCQ CQNGGTCDRF SGCVCPSGWH GVHCEKSDRI PQILNMASEL
   361  EFNLETMPRI NCAAAGNPFP VRGSIELRKP DGTVLLSTKA IVEPEKTTAE FEVPRLVLAD
   421  SGFWECRVST SGGQDSRRFK VNVKVPPVPL AAPRLLTKQS RQLVVSPLVS FSGDGPISTV
   481  RLHYRPQDST MDWSTIVVDP SENVTLMNLR PKTGYSVRVQ LSRPGEGGEG AWGPPTLMTT
   541  DCPEPLLQPW LEGWHVEGTD RLRVSWSLPL VPGPLVGDGF LLRLWDGTRG QERRENVSSP
   601  QARTALLTGL TPGTHYQLDV QLYHCTLLGP ASPPAHVLLP PSGPPAPRHL HAQALSDSEI
   661  QLTWKHPEAL PGPISKYVVE VQVAGGAGDP LWIDVDRPEE TSTIIRGLNA STRYLFRMRA
   721  SIQGLGDWSN TVEESTLGNG LQAEGPVQES RAAEEGLDQQ LILAVVGSVS ATCLTILAAL
   781  LTLVCIRRSC LHRRRTFTYQ SGSGEETILQ FSSGTLTLTR RPKLQPEPLS YPVLEWEDIT
   841  FEDLIGEGNF GQVIRAMIKK DGLKMNAAIK MLKEYASEND HRDFAGELEV LCKLGHHPNI
   901  INLLGACKNR GYLYIAIEYA PYGNLLDFLR KSRVLETDPA FAREHGTAST LSSRQLLRFA
   961  SDAANGMQYL SEKQFIHRDL AARNVLVGEN LASKIADFGL SRGEEVYVKK TMGRLPVRWM
  1021  AIESLNYSVY TTKSDVWSFG VLLWEIVSLG GTPYCGMTCA ELYEKLPQGY RMEQPRNCDD
  1081  EVYELMRQCW RDRPYERPPF AQIALQLGRM LEARKAYVNM SLFENFTYAG IDATAEEA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TIE1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

46 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TIE1.

Disease | AllUniProt

Conditions TIE1 is implicated in, by any mechanism.

• Lymphatic malformation 11 (LMPHM11) MIM:619401

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 205 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Lymphatic malformation 11

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.89

gnomAD pLI

0

gnomAD missense Z

1.51

DepMap mean gene effect

-0.15

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• aortic valve morphogenesis
• cell surface receptor protein tyrosine kinase signaling pathway
• in utero embryonic development
• lymphatic endothelial cell differentiation
• mesoderm development
• negative regulation of angiogenesis
• negative regulation of cell migration
• plasma membrane fusion
• positive regulation of angiogenesis
• regulation of endothelial cell proliferation
• regulation of extracellular matrix assembly
• response to retinoic acid
• signal transduction
• tissue remodeling
• vasculogenesis
• branching involved in lymph vessel morphogenesis

Molecular functions

• ATP binding
• transmembrane receptor protein tyrosine kinase activity

Cellular components

• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• EGF-like domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Immunoglobulin domain subtype
• Fibronectin type III
• Tyrosine-protein kinase, active site
• Protein kinase-like domain superfamily
• Immunoglobulin-like beta-sandwich domain
• Immunoglobulin-like fold
• Protein kinase, ATP binding site
• Tyrosine-protein kinase, catalytic domain
• Fibronectin type III superfamily
• Immunoglobulin-like domain superfamily
• Receptor Tyrosine Kinase
• Fibronectin type III domain
• Immunoglobulin domain
• Protein tyrosine and serine/threonine kinase

KeywordsUniProt

• Angiogenesis
• ATP-binding
• Cell membrane
• Disulfide bond
• EGF-like domain
• Glycoprotein
• Immunoglobulin domain
• Kinase
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transferase
• Transmembrane
• Transmembrane helix
• Tyrosine-protein kinase

InteractionsUniProt · HPA

Protein binding partners of TIE1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SVEP1