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P35590 (TIE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase receptor Tie-1

EC=2.7.10.1
Gene names
Name:TIE1
Synonyms:TIE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1138 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transmembrane tyrosine-protein kinase that may modulate TEK/TIE2 activity and contribute to the regulation of angiogenesis. Ref.8

Catalytic activity

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

Subunit structure

Heterodimer with TEK/TIE2.

Subcellular location

Cell membrane; Single-pass type I membrane protein Ref.7 Ref.8.

Tissue specificity

Specifically expressed in developing vascular endothelial cells.

Post-translational modification

Phosphorylated on tyrosine residues in response to ANGPT1, most likely by TEK/TIE2. Ref.7

Sequence similarities

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

Contains 3 EGF-like domains.

Contains 3 fibronectin type-III domains.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainEGF-like domain
Immunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

mesoderm development

Traceable author statement PubMed 7596437. Source: ProtInc

negative regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

peptidyl-tyrosine phosphorylation

Traceable author statement Ref.1. Source: GOC

plasma membrane fusion

Inferred from electronic annotation. Source: Ensembl

response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement Ref.1. Source: ProtInc

vasculogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 21982860. Source: IntAct

transmembrane receptor protein tyrosine kinase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PSG5Q152383EBI-2256865,EBI-4314891

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P35590-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P35590-2)

The sequence of this isoform differs from the canonical sequence as follows:
     348-379: DRIPQILNMASELEFNLETMPRINCAAAGNPF → GWRDWVDTSTEKQNTDEGRFGGHVSAPVGAPG
     380-1138: Missing.
Isoform 3 (identifier: P35590-3)

The sequence of this isoform differs from the canonical sequence as follows:
     305-317: ACAPGHFGADCRL → VHQGHCGAREDHS
     318-1138: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Ref.6
Chain22 – 11381117Tyrosine-protein kinase receptor Tie-1
PRO_0000024471

Regions

Topological domain22 – 759738Extracellular Potential
Transmembrane760 – 78425Helical; Potential
Topological domain785 – 1138354Cytoplasmic Potential
Domain43 – 10563Ig-like C2-type 1
Domain214 – 25643EGF-like 1
Domain258 – 30346EGF-like 2
Domain305 – 34541EGF-like 3
Domain372 – 42655Ig-like C2-type 2
Domain446 – 545100Fibronectin type-III 1
Domain548 – 64295Fibronectin type-III 2
Domain646 – 73994Fibronectin type-III 3
Domain839 – 1118280Protein kinase
Nucleotide binding845 – 8539ATP By similarity

Sites

Active site9791Proton acceptor By similarity
Binding site8701ATP By similarity

Amino acid modifications

Modified residue10071Phosphotyrosine; by autocatalysis By similarity
Glycosylation831N-linked (GlcNAc...) Potential
Glycosylation1611N-linked (GlcNAc...) Potential
Glycosylation5031N-linked (GlcNAc...) Potential
Glycosylation5961N-linked (GlcNAc...) Potential
Glycosylation7091N-linked (GlcNAc...) Potential
Disulfide bond228 ↔ 237 By similarity
Disulfide bond231 ↔ 244 By similarity
Disulfide bond246 ↔ 255 By similarity
Disulfide bond315 ↔ 327 By similarity
Disulfide bond321 ↔ 333 By similarity
Disulfide bond335 ↔ 344 By similarity

Natural variations

Alternative sequence305 – 31713ACAPG…ADCRL → VHQGHCGAREDHS in isoform 3.
VSP_047607
Alternative sequence318 – 1138821Missing in isoform 3.
VSP_047608
Alternative sequence348 – 37932DRIPQ…AGNPF → GWRDWVDTSTEKQNTDEGRF GGHVSAPVGAPG in isoform 2.
VSP_047609
Alternative sequence380 – 1138759Missing in isoform 2.
VSP_047610
Natural variant4481V → M. Ref.9
Corresponds to variant rs56302794 [ dbSNP | Ensembl ].
VAR_041852
Natural variant11041A → V. Ref.9
Corresponds to variant rs35573981 [ dbSNP | Ensembl ].
VAR_041853
Natural variant11091R → H. Ref.9
Corresponds to variant rs34993202 [ dbSNP | Ensembl ].
VAR_041854

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 1994. Version 1.
Checksum: 3B42BE33678C58A1

FASTA1,138125,090
        10         20         30         40         50         60 
MVWRVPPFLL PILFLASHVG AAVDLTLLAN LRLTDPQRFF LTCVSGEAGA GRGSDAWGPP 

        70         80         90        100        110        120 
LLLEKDDRIV RTPPGPPLRL ARNGSHQVTL RGFSKPSDLV GVFSCVGGAG ARRTRVIYVH 

       130        140        150        160        170        180 
NSPGAHLLPD KVTHTVNKGD TAVLSARVHK EKQTDVIWKS NGSYFYTLDW HEAQDGRFLL 

       190        200        210        220        230        240 
QLPNVQPPSS GIYSATYLEA SPLGSAFFRL IVRGCGAGRW GPGCTKECPG CLHGGVCHDH 

       250        260        270        280        290        300 
DGECVCPPGF TGTRCEQACR EGRFGQSCQE QCPGISGCRG LTFCLPDPYG CSCGSGWRGS 

       310        320        330        340        350        360 
QCQEACAPGH FGADCRLQCQ CQNGGTCDRF SGCVCPSGWH GVHCEKSDRI PQILNMASEL 

       370        380        390        400        410        420 
EFNLETMPRI NCAAAGNPFP VRGSIELRKP DGTVLLSTKA IVEPEKTTAE FEVPRLVLAD 

       430        440        450        460        470        480 
SGFWECRVST SGGQDSRRFK VNVKVPPVPL AAPRLLTKQS RQLVVSPLVS FSGDGPISTV 

       490        500        510        520        530        540 
RLHYRPQDST MDWSTIVVDP SENVTLMNLR PKTGYSVRVQ LSRPGEGGEG AWGPPTLMTT 

       550        560        570        580        590        600 
DCPEPLLQPW LEGWHVEGTD RLRVSWSLPL VPGPLVGDGF LLRLWDGTRG QERRENVSSP 

       610        620        630        640        650        660 
QARTALLTGL TPGTHYQLDV QLYHCTLLGP ASPPAHVLLP PSGPPAPRHL HAQALSDSEI 

       670        680        690        700        710        720 
QLTWKHPEAL PGPISKYVVE VQVAGGAGDP LWIDVDRPEE TSTIIRGLNA STRYLFRMRA 

       730        740        750        760        770        780 
SIQGLGDWSN TVEESTLGNG LQAEGPVQES RAAEEGLDQQ LILAVVGSVS ATCLTILAAL 

       790        800        810        820        830        840 
LTLVCIRRSC LHRRRTFTYQ SGSGEETILQ FSSGTLTLTR RPKLQPEPLS YPVLEWEDIT 

       850        860        870        880        890        900 
FEDLIGEGNF GQVIRAMIKK DGLKMNAAIK MLKEYASEND HRDFAGELEV LCKLGHHPNI 

       910        920        930        940        950        960 
INLLGACKNR GYLYIAIEYA PYGNLLDFLR KSRVLETDPA FAREHGTAST LSSRQLLRFA 

       970        980        990       1000       1010       1020 
SDAANGMQYL SEKQFIHRDL AARNVLVGEN LASKIADFGL SRGEEVYVKK TMGRLPVRWM 

      1030       1040       1050       1060       1070       1080 
AIESLNYSVY TTKSDVWSFG VLLWEIVSLG GTPYCGMTCA ELYEKLPQGY RMEQPRNCDD 

      1090       1100       1110       1120       1130 
EVYELMRQCW RDRPYERPPF AQIALQLGRM LEARKAYVNM SLFENFTYAG IDATAEEA 

« Hide

Isoform 2 [UniParc].

Checksum: 8EACCD600795FF09
Show »

FASTA37940,616
Isoform 3 [UniParc].

Checksum: 456907881A613CE4
Show »

FASTA31734,138

References

« Hide 'large scale' references
[1]"A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains."
Partanen J., Armstrong E., Maekelae T.P., Korhonen J., Sandberg M., Renkonen R., Knuutila S., Huebner K., Alitalo K.
Mol. Cell. Biol. 12:1698-1707(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]Partanen J.M.
Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis."
Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.
Arthritis Res. Ther. 10:R73-R73(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[6]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 22-36.
[7]"Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2."
Saharinen P., Kerkela K., Ekman N., Marron M., Brindle N., Lee G.M., Augustin H., Koh G.Y., Alitalo K.
J. Cell Biol. 169:239-243(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TEK/TIE2, SUBCELLULAR LOCATION, PHOSPHORYLATION.
[8]"Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands."
Seegar T.C., Eller B., Tzvetkova-Robev D., Kolev M.V., Henderson S.C., Nikolov D.B., Barton W.A.
Mol. Cell 37:643-655(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TEK/TIE2, SUBCELLULAR LOCATION, FUNCTION.
[9]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-448; VAL-1104 AND HIS-1109.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X60957 mRNA. Translation: CAA43290.1.
EU826587 mRNA. Translation: ACF47623.1.
EU826588 mRNA. Translation: ACF47624.1.
AC093420 Genomic DNA. No translation available.
AL139289 Genomic DNA. No translation available.
BC038239 mRNA. Translation: AAH38239.1.
CCDSCCDS482.1. [P35590-1]
RefSeqNP_005415.1. NM_005424.4. [P35590-1]
UniGeneHs.78824.

3D structure databases

ProteinModelPortalP35590.
SMRP35590. Positions 22-523, 549-736, 772-1136.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112931. 8 interactions.
IntActP35590. 7 interactions.
MINTMINT-6773015.
STRING9606.ENSP00000361554.

Chemistry

BindingDBP35590.
ChEMBLCHEMBL5274.
GuidetoPHARMACOLOGY1841.

PTM databases

PhosphoSiteP35590.

Polymorphism databases

DMDM549081.

Proteomic databases

PaxDbP35590.
PRIDEP35590.

Protocols and materials databases

DNASU7075.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372476; ENSP00000361554; ENSG00000066056. [P35590-1]
ENST00000441333; ENSP00000401903; ENSG00000066056. [P35590-3]
ENST00000538015; ENSP00000440063; ENSG00000066056. [P35590-2]
GeneID7075.
KEGGhsa:7075.
UCSCuc001ciu.3. human. [P35590-1]

Organism-specific databases

CTD7075.
GeneCardsGC01P043766.
HGNCHGNC:11809. TIE1.
MIM600222. gene.
neXtProtNX_P35590.
PharmGKBPA36516.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000049232.
HOVERGENHBG007316.
InParanoidP35590.
KOK05120.
OMASDRIPQI.
PhylomeDBP35590.
TreeFamTF317568.

Enzyme and pathway databases

BRENDA2.7.10.1. 2681.
SignaLinkP35590.

Gene expression databases

ArrayExpressP35590.
BgeeP35590.
CleanExHS_TIE1.
GenevestigatorP35590.

Family and domain databases

Gene3D2.60.40.10. 5 hits.
InterProIPR000742. EG-like_dom.
IPR013032. EGF-like_CS.
IPR003961. Fibronectin_type3.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF00041. fn3. 3 hits.
PF12661. hEGF. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00181. EGF. 2 hits.
SM00060. FN3. 3 hits.
SM00409. IG. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
SSF56112. SSF56112. 1 hit.
PROSITEPS00022. EGF_1. 3 hits.
PS01186. EGF_2. 3 hits.
PS50026. EGF_3. 2 hits.
PS50853. FN3. 3 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi7075.
NextBio27671.
PROP35590.
SOURCESearch...

Entry information

Entry nameTIE1_HUMAN
AccessionPrimary (citable) accession number: P35590
Secondary accession number(s): B5A949, B5A950
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM