P35590 (TIE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase receptor Tie-1
EC=2.7.10.1

Gene names

Name:	TIE1
Synonyms:	TIE

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1138 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.6
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.5 Ref.6.
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.5
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 process	Angiogenesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: UniProtKB-KW in utero embryonic development Inferred from electronic annotation. Source: Compara mesoderm development Traceable author statement PubMed 7596437. Source: ProtInc negative regulation of angiogenesis Inferred from electronic annotation. Source: Compara negative regulation of cell migration Inferred from electronic annotation. Source: Compara plasma membrane fusion Inferred from electronic annotation. Source: Compara response to retinoic acid Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW transmembrane receptor protein tyrosine kinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSG5	Q15238	3	EBI-2256865,EBI-4314891

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Ref.4
	Chain	22 – 1138	1117	Tyrosine-protein kinase receptor Tie-1		PRO_0000024471
Regions
	Topological domain	22 – 759	738	Extracellular Potential
	Transmembrane	760 – 784	25	Helical; Potential
	Topological domain	785 – 1138	354	Cytoplasmic Potential
	Domain	43 – 105	63	Ig-like C2-type 1
	Domain	214 – 256	43	EGF-like 1
	Domain	258 – 303	46	EGF-like 2
	Domain	305 – 345	41	EGF-like 3
	Domain	372 – 426	55	Ig-like C2-type 2
	Domain	446 – 537	92	Fibronectin type-III 1
	Domain	545 – 637	93	Fibronectin type-III 2
	Domain	644 – 736	93	Fibronectin type-III 3
	Domain	839 – 1118	280	Protein kinase
	Nucleotide binding	845 – 853	9	ATP By similarity
Sites
	Active site	979	1	Proton acceptor By similarity
	Binding site	870	1	ATP By similarity
Amino acid modifications
	Modified residue	1007	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	83	1	N-linked (GlcNAc...) Potential
	Glycosylation	161	1	N-linked (GlcNAc...) Potential
	Glycosylation	503	1	N-linked (GlcNAc...) Potential
	Glycosylation	596	1	N-linked (GlcNAc...) Potential
	Glycosylation	709	1	N-linked (GlcNAc...) Potential
	Disulfide bond	228 ↔ 237		By similarity
	Disulfide bond	231 ↔ 244		By similarity
	Disulfide bond	246 ↔ 255		By similarity
	Disulfide bond	315 ↔ 327		By similarity
	Disulfide bond	321 ↔ 333		By similarity
	Disulfide bond	335 ↔ 344		By similarity
Natural variations
	Natural variant	448	1	V → M. Ref.7 Corresponds to variant rs56302794 [ dbSNP | Ensembl ].		VAR_041852
	Natural variant	1104	1	A → V. Ref.7 Corresponds to variant rs35573981 [ dbSNP | Ensembl ].		VAR_041853
	Natural variant	1109	1	R → H. Ref.7 Corresponds to variant rs34993202 [ dbSNP | Ensembl ].		VAR_041854

Sequences

	Sequence		Length	Mass (Da)
	P35590 [UniParc]. Last modified June 1, 1994. Version 1. Checksum: 3B42BE33678C58A1	FASTA	1,138	125,090
	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

References

	« Hide 'large scale' referencesShow '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].
[2]	Partanen J.M. Submitted (JUL-1993) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"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]. Tissue: Lung.
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"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. , 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. BC038239 mRNA. Translation: AAH38239.1.
IPI	IPI00019530.
RefSeq	NP_005415.1. NM_005424.4.
UniGene	Hs.78824.
3D structure databases
ProteinModelPortal	P35590.
ModBase	Search...
Protein-protein interaction databases
IntAct	P35590. 6 interactions.
STRING	9606.ENSP00000361554.
PTM databases
PhosphoSite	P35590.
Polymorphism databases
DMDM	549081.
Proteomic databases
PaxDb	P35590.
PRIDE	P35590.
Protocols and materials databases
DNASU	7075.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000372476; ENSP00000361554; ENSG00000066056.
GeneID	7075.
KEGG	hsa:7075.
UCSC	uc001ciu.3. human.
Organism-specific databases
CTD	7075.
GeneCards	GC01P043766.
HGNC	HGNC:11809. TIE1.
MIM	600222. gene.
neXtProt	NX_P35590.
PharmGKB	PA36516.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000049232.
HOVERGEN	HBG007316.
InParanoid	P35590.
KO	K05120.
OMA	SDRIPQI.
OrthoDB	EOG4Q84WP.
PhylomeDB	P35590.
Enzyme and pathway databases
BRENDA	2.7.10.1. 2681.
Gene expression databases
ArrayExpress	P35590.
Bgee	P35590.
CleanEx	HS_TIE1.
Genevestigator	P35590.
GermOnline	ENSG00000066056. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 5 hits.
InterPro	IPR000742. EG-like_dom. IPR013032. EGF-like_CS. IPR003961. Fibronectin_type3. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. [Graphical view]
Pfam	PF00041. fn3. 3 hits. PF12661. hEGF. 1 hit. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00181. EGF. 2 hits. SM00060. FN3. 3 hits. SM00409. IG. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 3 hits. SSF56112. Kinase_like. 1 hit.
PROSITE	PS00022. 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]
ProtoNet	Search...
Other
BindingDB	P35590.
ChEMBL	CHEMBL5274.
GenomeRNAi	7075.
NextBio	27671.
SOURCE	Search...

Entry information

Entry name

TIE1_HUMAN

Accession

Primary (citable) accession number: P35590

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	June 1, 1994
Last modified:	May 1, 2013
This is version 136 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.