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TIE1 (tyrosine kinase with immunoglobulin-like and EGF-like domains 1)

Written2012-03Pipsa Saharinen
Molecular Cancer Biology Program, Research Programs Unit, Biomedicum Helsinki, Haartmaninkatu 8, P O B 63, FIN-00014 University of Helsinki, Finland

(Note : for Links provided by Atlas : click)

Identity

Alias_namesTIE
tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 1
tyrosine kinase with immunoglobulin-like and EGF-like domains 1
Alias_symbol (synonym)JTK14
HGNC (Hugo) TIE1
LocusID (NCBI) 7075
Atlas_Id 42560
Location 1p34.2  [Link to chromosome band 1p34]
Location_base_pair Starts at 43766566 and ends at 43788781 bp from pter ( according to hg19-Feb_2009)  [Mapping TIE1.png]
Fusion genes
(updated 2016)
TIE1 (1p34.2) / DIP2C (10p15.3)
Note Receptor tyrosine kinase, member of the TIE family (other member: TIE2/TEK). Highly conserved sequence across vertebrate species, with greatest amino acid homology occurring in the kinase domain.

DNA/RNA

 
  The genomic (top) and the protein domain structures (below) of human TIE1. Black boxes represent exons with intervening intron sequences (lines), light gray boxes represent non-coding sequences of first and last exons. Exon length (black text) and intron length of the longest introns (pink) are indicated in nucleotides. The protein domain coding regions of exons are indicated with colours according to the TIE1 protein domain structure. SS= signal sequence, Ig= immunoglobulin-like domain, EGF= epidermal growth factor-like domain, FN3= fibronectin type-III domain, TM= transmembrane domain, TK= tyrosine kinase domain. Protein domain prediction was performed using (SMART). The crystal structure for Tie2 shows the existence of a third Ig-like domain, immediately after the SS (Barton et al., 2006), and homology modeling of Tie1 predicts a similar fold (Seegar et al., 2010).
Description The human TIE1 gene spans 22115 bp, encoding for 23 exons in forward strand.
Transcription Longest mRNA contains 3882 bp. Alternatively spliced forms have been reported, including transcript variant 5 (EU826590.1) coding for a soluble TIE1 ectodomain (Jin et al., 2008).

Protein

Note See figure above.
Description Human TIE1 contains 1138 aa. It belongs to the protein kinase superfamily, protein receptor tyrosine kinase family, TIE subfamily. It contains 3 Ig (immunoglobulin)-like domains (I set type), 3 EGF (epidermal growth factor)-like domains, 3 fibronectin type-III domains, a single transmembrane domain and 1 intracellular split tyrosine kinase domain (Partanen et al., 1992).
Expression TIE1 is almost exclusively expressed in endothelial cells both in human and in mouse. High expression of TIE1 mRNA is found in adult lung, heart, and placenta, some expression in kidney, whereas muscle, brain, liver and pancreas contain less TIE1 mRNA. Tie1 mRNA is present widely in fetal tissues starting at embryonic day 8,5 (Korhonen et al., 1992). Tie1 mRNA is detected in differentiating angioblasts of the head mesenchyme, in the splanchnopleure and dorsal aorta as well as in migrating endothelial cells of the developing heart, in the heart endocardium and in the endothelial cells forming the lung vasculature (Korhonen et al., 1992).
TIE1 is also expressed on cultured endothelial cells, some haemopoietic progenitor cells, some myeloid leukemia cell lines having erythroid and megakaryoblastoid characteristics (Batard et al., 1996) and in adult acute myelogenous leukemia (Kivivuori et al., 2007). TIE1 expression is increased in angiogenic endothelial cells during wound-healing, in proliferating ovarial capillaries during hormone-induced superovulation and in tumor blood vessels (Korhonen et al., 1992; Kaipainen et al., 1994). Tie1 is downregulated in endothelial cells by shear stress (Chen-Konak et al., 2003), but specifically induced in the mouse vasculature by disturbed flow in vascular bifurcations and branching points along the arteries (Porat et al., 2004).
TIE1 along with ANGPT2 and TEK mRNAs were strongly expressed in cells of Kaposi's sarcoma tumor cells, and cutaneous angiosarcomas, in contrast to the focal low-level expression in normal skin biopsies (Brown et al., 2000).
Localisation Cell membrane.
Function Studies of Tie1 gene targeted mice have revealed that Tie1 is critical for the development of blood (Puri et al., 1995) and lymphatic vasculatures (D'Amico et al., 2010; Qu et al., 2010) after midgestation. Tie1 is essential for endothelial cell survival in the developing microvasculature undergoing angiogenic sprouting, and essentially in all blood vessels in adult (Partanen et al., 1996). Tie1-/- embryos die around embryonic day 13,5, depending on the background (Puri et al., 1995; D'Amico et al., 2010). The Tie1 deficient or hypomorphic embryos show also signs of edema, due to lymphatic defects involving abnormally patterned lymph sacs and peripheral lymphatic vessels (D'Amico et al., 2010; Qu et al., 2010).
The molecular function of TIE1 is not completely understood, as it does not directly bind the angiopoietin growth factors, which are the ligands for TEK (TIE2). However, TIE1 tyrosine phosphorylation is induced by angiopoietin-1 (Saharinen et al., 2005; Yuan et al., 2007), most likely in a complex with TEK (Marron et al., 2000; Saharinen et al., 2005). Angiopoietins activate TEK in a unique manner, which involves the translocation of TEK to endothelial cell-cell contacts, and TIE1 is also present in these complexes (Saharinen et al., 2008). Activation of the TIE1 kinase activity using chimeric TIE1 receptors was found to result in the activation of the Akt pathway (Kontos et al., 2002). The TIE1 ectodomain is proteolytically cleaved, and the cleavage is enhanced by PMA, VEGF and TNF-α (Yabkowitz et al., 1999). The proteolytic processing of TIE1 may regulate TEK activity (Marron et al., 2007).
The deletion of both Tie1 and Tek results in a more severe phenotype than the deletions of either Tie1 or Tek alone (Sato et al., 1995; Puri et al., 1999). The deletion of both Tie1 and Angpt1 resulted in impaired development of the right-hand, but not left-hand side venous system in the mouse embryo (Loughna and Sato, 2001).
TIE1 has been implicated as a proinflammatory gene and its silencing in cultured endothelial cells reduced the expression of proinflammatory genes (Chan and Sukhatme, 2009), while TIE1 overexpression upregulated adhesion molecules including VCAM-1, E-selectin and ICAM-1 (Chan et al., 2008).
Homology H. sapiens: TIE1; M. musculus: Tie1; R. novergicus: Tie1; D. rerio: tie1; X. tropicalis: tie1.

Mutations

Somatic Somatic missense mutations and synonymous substitutions in TIE1 have been detected in human cancers, but their significance remains to be found out.

Implicated in

Note
Entity Various diseases
Note TIE1 has not been directly shown to be involved in any human diseases. Most of the information concerning Tie1 function has been retrieved from animal models.
  
Entity Gastric cancer
Note TIE1 expression has been detected in gastric adenocarcinoma tissues where its expression inversely correlated with patients' survival (Lin et al., 1999).
  
Entity Atherosclerosis
Note Tie1 is upregulated in emerging atherosclerotic plaques and around developing aneurysms (Porat et al., 2004), and Tie1+/- mice bred to the ApoE-deficient background displayed a 35% reduction in atherosclerosis relative to Tie1+/+;Apoe-/- mice (Woo et al., 2011).
  

To be noted

Recently, ANGPT2, a ligand for TEK, has been identified as a promising target for novel anti-angiogenic tumor therapies, and inhibition of ANGPT2 has resulted in inhibition of tumor growth, angiogenesis, lymphangiogenesis and metastasis in preclinical models (Oliner et al., 2004; Brown et al., 2010; Mazzieri et al., 2011; Holopainen et al., 2012). In a phase II clinical trial ANGPT1/ANGPT2 dual blocking peptibodies in combination with paclitaxel prolonged the progression-free survival of the ovarian cancer patients (Karlan et al., 2012). In addition, the adenoviral delivery of anti-Tek intrabodies impaired tumor growth in preclinical models (Popkov et al., 2005). ANGPT1 appears to mediate vascular normalization of the tumor blood vessels during VEGF or ANGPT2 blocking anti-angiogenic therapy (Winkler et al., 2004; Falcón et al., 2009). Although evidence for the function of TIE1 in tumors is lacking, it should be noted that via interaction with TEK, TIE1 might be involved in tumor angiogenesis and progression.

Bibliography

Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex.
Barton WA, Tzvetkova-Robev D, Miranda EP, Kolev MV, Rajashankar KR, Himanen JP, Nikolov DB.
Nat Struct Mol Biol. 2006 Jun;13(6):524-32. Epub 2006 May 28.
PMID 16732286
 
The Tie receptor tyrosine kinase is expressed by human hematopoietic progenitor cells and by a subset of megakaryocytic cells.
Batard P, Sansilvestri P, Scheinecker C, Knapp W, Debili N, Vainchenker W, Buhring HJ, Monier MN, Kukk E, Partanen J, Matikainen MT, Alitalo R, Hatzfeld J, Alitalo K.
Blood. 1996 Mar 15;87(6):2212-20.
PMID 8630381
 
A human monoclonal anti-ANG2 antibody leads to broad antitumor activity in combination with VEGF inhibitors and chemotherapy agents in preclinical models.
Brown JL, Cao ZA, Pinzon-Ortiz M, Kendrew J, Reimer C, Wen S, Zhou JQ, Tabrizi M, Emery S, McDermott B, Pablo L, McCoon P, Bedian V, Blakey DC.
Mol Cancer Ther. 2010 Jan;9(1):145-56. Epub 2010 Jan 6.
PMID 20053776
 
Expression of Tie1, Tie2, and angiopoietins 1, 2, and 4 in Kaposi's sarcoma and cutaneous angiosarcoma.
Brown LF, Dezube BJ, Tognazzi K, Dvorak HF, Yancopoulos GD.
Am J Pathol. 2000 Jun;156(6):2179-83.
PMID 10854238
 
Suppression of Tie-1 in endothelial cells in vitro induces a change in the genome-wide expression profile reflecting an inflammatory function.
Chan B, Sukhatme VP.
FEBS Lett. 2009 Mar 18;583(6):1023-8. Epub 2009 Feb 21.
PMID 19236867
 
Receptor tyrosine kinase Tie-1 overexpression in endothelial cells upregulates adhesion molecules.
Chan B, Yuan HT, Ananth Karumanchi S, Sukhatme VP.
Biochem Biophys Res Commun. 2008 Jul 4;371(3):475-9. Epub 2008 Apr 28.
PMID 18448073
 
Transcriptional and post-translation regulation of the Tie1 receptor by fluid shear stress changes in vascular endothelial cells.
Chen-Konak L, Guetta-Shubin Y, Yahav H, Shay-Salit A, Zilberman M, Binah O, Resnick N.
FASEB J. 2003 Nov;17(14):2121-3. Epub 2003 Sep 18.
PMID 14500555
 
Loss of endothelial Tie1 receptor impairs lymphatic vessel development-brief report.
D'Amico G, Korhonen EA, Waltari M, Saharinen P, Laakkonen P, Alitalo K.
Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):207-9. Epub 2009 Nov 12.
PMID 19910638
 
Contrasting actions of selective inhibitors of angiopoietin-1 and angiopoietin-2 on the normalization of tumor blood vessels.
Falcon BL, Hashizume H, Koumoutsakos P, Chou J, Bready JV, Coxon A, Oliner JD, McDonald DM.
Am J Pathol. 2009 Nov;175(5):2159-70. Epub 2009 Oct 8.
PMID 19815705
 
Effects of angiopoietin-2-blocking antibody on endothelial cell-cell junctions and lung metastasis.
Holopainen T, Saharinen P, D'Amico G, Lampinen A, Eklund L, Sormunen R, Anisimov A, Zarkada G, Lohela M, Helotera H, Tammela T, Benjamin LE, Yla-Herttuala S, Leow CC, Koh GY, Alitalo K.
J Natl Cancer Inst. 2012 Mar 21;104(6):461-75. Epub 2012 Feb 17.
PMID 22343031
 
Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis.
Jin P, Zhang J, Sumariwalla PF, Ni I, Jorgensen B, Crawford D, Phillips S, Feldmann M, Shepard HM, Paleolog EM.
Arthritis Res Ther. 2008;10(4):R73. Epub 2008 Jul 1.
PMID 18593464
 
Enhanced expression of the tie receptor tyrosine kinase mesenger RNA in the vascular endothelium of metastatic melanomas.
Kaipainen A, Vlaykova T, Hatva E, Bohling T, Jekunen A, Pyrhonen S, Alitalo K.
Cancer Res. 1994 Dec 15;54(24):6571-7.
PMID 7987857
 
Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients with recurrent ovarian cancer.
Karlan BY, Oza AM, Richardson GE, Provencher DM, Hansen VL, Buck M, Chambers SK, Ghatage P, Pippitt CH Jr, Brown JV 3rd, Covens A, Nagarkar RV, Davy M, Leath CA 3rd, Nguyen H, Stepan DE, Weinreich DM, Tassoudji M, Sun YN, Vergote IB.
J Clin Oncol. 2012 Feb 1;30(4):362-71. Epub 2011 Dec 19.
PMID 22184370
 
Expression of vascular endothelial growth factor receptor 3 and Tie1 tyrosine kinase receptor on acute leukemia cells.
Kivivuori SM, Siitonen S, Porkka K, Vettenranta K, Alitalo R, Saarinen-Pihkala U.
Pediatr Blood Cancer. 2007 Apr;48(4):387-92.
PMID 16685739
 
The endothelial receptor tyrosine kinase Tie1 activates phosphatidylinositol 3-kinase and Akt to inhibit apoptosis.
Kontos CD, Cha EH, York JD, Peters KG.
Mol Cell Biol. 2002 Mar;22(6):1704-13.
PMID 11865050
 
Enhanced expression of the tie receptor tyrosine kinase in endothelial cells during neovascularization.
Korhonen J, Partanen J, Armstrong E, Vaahtokari A, Elenius K, Jalkanen M, Alitalo K.
Blood. 1992 Nov 15;80(10):2548-55.
PMID 1384789
 
tie-1 protein tyrosine kinase: a novel independent prognostic marker for gastric cancer.
Lin WC, Li AF, Chi CW, Chung WW, Huang CL, Lui WY, Kung HJ, Wu CW.
Clin Cancer Res. 1999 Jul;5(7):1745-51.
PMID 10430078
 
A combinatorial role of angiopoietin-1 and orphan receptor TIE1 pathways in establishing vascular polarity during angiogenesis.
Loughna S, Sato TN.
Mol Cell. 2001 Jan;7(1):233-9.
PMID 11172728
 
Evidence for heterotypic interaction between the receptor tyrosine kinases TIE-1 and TIE-2.
Marron MB, Hughes DP, Edge MD, Forder CL, Brindle NP.
J Biol Chem. 2000 Dec 15;275(50):39741-6.
PMID 10995770
 
Regulated proteolytic processing of Tie1 modulates ligand responsiveness of the receptor-tyrosine kinase Tie2.
Marron MB, Singh H, Tahir TA, Kavumkal J, Kim HZ, Koh GY, Brindle NP.
J Biol Chem. 2007 Oct 19;282(42):30509-17. Epub 2007 Aug 29.
PMID 17728252
 
Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells.
Mazzieri R, Pucci F, Moi D, Zonari E, Ranghetti A, Berti A, Politi LS, Gentner B, Brown JL, Naldini L, De Palma M.
Cancer Cell. 2011 Apr 12;19(4):512-26.
PMID 21481792
 
Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2.
Oliner J, Min H, Leal J, Yu D, Rao S, You E, Tang X, Kim H, Meyer S, Han SJ, Hawkins N, Rosenfeld R, Davy E, Graham K, Jacobsen F, Stevenson S, Ho J, Chen Q, Hartmann T, Michaels M, Kelley M, Li L, Sitney K, Martin F, Sun JR, Zhang N, Lu J, Estrada J, Kumar R, Coxon A, Kaufman S, Pretorius J, Scully S, Cattley R, Payton M, Coats S, Nguyen L, Desilva B, Ndifor A, Hayward I, Radinsky R, Boone T, Kendall R.
Cancer Cell. 2004 Nov;6(5):507-16.
PMID 15542434
 
Cell autonomous functions of the receptor tyrosine kinase TIE in a late phase of angiogenic capillary growth and endothelial cell survival during murine development.
Partanen J, Puri MC, Schwartz L, Fischer KD, Bernstein A, Rossant J.
Development. 1996 Oct;122(10):3013-21.
PMID 8898215
 
Targeting tumor angiogenesis with adenovirus-delivered anti-Tie-2 intrabody.
Popkov M, Jendreyko N, McGavern DB, Rader C, Barbas CF 3rd.
Cancer Res. 2005 Feb 1;65(3):972-81.
PMID 15705898
 
Specific induction of tie1 promoter by disturbed flow in atherosclerosis-prone vascular niches and flow-obstructing pathologies.
Porat RM, Grunewald M, Globerman A, Itin A, Barshtein G, Alhonen L, Alitalo K, Keshet E.
Circ Res. 2004 Feb 20;94(3):394-401. Epub 2003 Dec 11.
PMID 14670840
 
Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development.
Puri MC, Partanen J, Rossant J, Bernstein A.
Development. 1999 Oct;126(20):4569-80.
PMID 10498691
 
The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells.
Puri MC, Rossant J, Alitalo K, Bernstein A, Partanen J.
EMBO J. 1995 Dec 1;14(23):5884-91.
PMID 8846781
 
Abnormal embryonic lymphatic vessel development in Tie1 hypomorphic mice.
Qu X, Tompkins K, Batts LE, Puri M, Baldwin S.
Development. 2010 Apr;137(8):1285-95. Epub 2010 Mar 10.
PMID 20223757
 
Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts.
Saharinen P, Eklund L, Miettinen J, Wirkkala R, Anisimov A, Winderlich M, Nottebaum A, Vestweber D, Deutsch U, Koh GY, Olsen BR, Alitalo K.
Nat Cell Biol. 2008 May;10(5):527-37. Epub 2008 Apr 20.
PMID 18425119
 
Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation.
Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, Gridley T, Wolburg H, Risau W, Qin Y.
Nature. 1995 Jul 6;376(6535):70-4.
PMID 7596437
 
Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands.
Seegar TC, Eller B, Tzvetkova-Robev D, Kolev MV, Henderson SC, Nikolov DB, Barton WA.
Mol Cell. 2010 Mar 12;37(5):643-55.
PMID 20227369
 
Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases.
Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK.
Cancer Cell. 2004 Dec;6(6):553-63.
PMID 15607960
 
Tie1 attenuation reduces murine atherosclerosis in a dose-dependent and shear stress-specific manner.
Woo KV, Qu X, Babaev VR, Linton MF, Guzman RJ, Fazio S, Baldwin HS.
J Clin Invest. 2011 Apr;121(4):1624-35. doi: 10.1172/JCI42040. Epub 2011 Mar 7.
PMID 21383501
 
Inflammatory cytokines and vascular endothelial growth factor stimulate the release of soluble tie receptor from human endothelial cells via metalloprotease activation.
Yabkowitz R, Meyer S, Black T, Elliott G, Merewether LA, Yamane HK.
Blood. 1999 Mar 15;93(6):1969-79.
PMID 10068670
 
Activation of the orphan endothelial receptor Tie1 modifies Tie2-mediated intracellular signaling and cell survival.
Yuan HT, Venkatesha S, Chan B, Deutsch U, Mammoto T, Sukhatme VP, Woolf AS, Karumanchi SA.
FASEB J. 2007 Oct;21(12):3171-83. Epub 2007 May 15.
PMID 17504972
 

Citation

This paper should be referenced as such :
Saharinen, P
TIE1 (tyrosine kinase with immunoglobulin-like, EGF-like domains 1)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(8):559-562.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TIE1ID42560ch1p34.html


External links

Nomenclature
HGNC (Hugo)TIE1   11809
Cards
AtlasTIE1ID42560ch1p34
Entrez_Gene (NCBI)TIE1  7075  tyrosine kinase with immunoglobulin like and EGF like domains 1
AliasesJTK14; TIE
GeneCards (Weizmann)TIE1
Ensembl hg19 (Hinxton)ENSG00000066056 [Gene_View]  chr1:43766566-43788781 [Contig_View]  TIE1 [Vega]
Ensembl hg38 (Hinxton)ENSG00000066056 [Gene_View]  chr1:43766566-43788781 [Contig_View]  TIE1 [Vega]
ICGC DataPortalENSG00000066056
TCGA cBioPortalTIE1
AceView (NCBI)TIE1
Genatlas (Paris)TIE1
WikiGenes7075
SOURCE (Princeton)TIE1
Genetics Home Reference (NIH)TIE1
Genomic and cartography
GoldenPath hg19 (UCSC)TIE1  -     chr1:43766566-43788781 +  1p34-p33   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)TIE1  -     1p34-p33   [Description]    (hg38-Dec_2013)
EnsemblTIE1 - 1p34-p33 [CytoView hg19]  TIE1 - 1p34-p33 [CytoView hg38]
Mapping of homologs : NCBITIE1 [Mapview hg19]  TIE1 [Mapview hg38]
OMIM600222   
Gene and transcription
Genbank (Entrez)AF217976 AK225560 AK296735 AK300399 AK300623
RefSeq transcript (Entrez)NM_001253357 NM_005424
RefSeq genomic (Entrez)NC_000001 NC_018912 NG_030673 NT_032977 NW_004929290
Consensus coding sequences : CCDS (NCBI)TIE1
Cluster EST : UnigeneHs.78824 [ NCBI ]
CGAP (NCI)Hs.78824
Alternative Splicing GalleryENSG00000066056
Gene ExpressionTIE1 [ NCBI-GEO ]   TIE1 [ EBI - ARRAY_EXPRESS ]   TIE1 [ SEEK ]   TIE1 [ MEM ]
Gene Expression Viewer (FireBrowse)TIE1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7075
GTEX Portal (Tissue expression)TIE1
Protein : pattern, domain, 3D structure
UniProt/SwissProtP35590   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP35590  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP35590
Splice isoforms : SwissVarP35590
Catalytic activity : Enzyme2.7.10.1 [ Enzyme-Expasy ]   2.7.10.12.7.10.1 [ IntEnz-EBI ]   2.7.10.1 [ BRENDA ]   2.7.10.1 [ KEGG ]   
PhosPhoSitePlusP35590
Domaine pattern : Prosite (Expaxy)EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)    FN3 (PS50853)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)   
Domains : Interpro (EBI)EGF-like_CS    EGF-like_dom    FN3_dom    Ig-like_dom    Ig-like_fold    Ig_sub    Immunoglobulin    Kinase-like_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    Tyr_kinase_AS    Tyr_kinase_cat_dom   
Domain families : Pfam (Sanger)fn3 (PF00041)    hEGF (PF12661)    ig (PF00047)    Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam00041    pfam12661    pfam00047    pfam07714   
Domain families : Smart (EMBL)EGF (SM00181)  FN3 (SM00060)  IG (SM00409)  TyrKc (SM00219)  
Conserved Domain (NCBI)TIE1
DMDM Disease mutations7075
Blocks (Seattle)TIE1
SuperfamilyP35590
Human Protein AtlasENSG00000066056
Peptide AtlasP35590
HPRD02572
IPIIPI00019530   IPI01018826   IPI00936406   IPI01009976   IPI00910840   IPI00909918   IPI00646429   
Protein Interaction databases
DIP (DOE-UCLA)P35590
IntAct (EBI)P35590
FunCoupENSG00000066056
BioGRIDTIE1
STRING (EMBL)TIE1
ZODIACTIE1
Ontologies - Pathways
QuickGOP35590
Ontology : AmiGOangiogenesis  vasculogenesis  in utero embryonic development  transmembrane receptor protein tyrosine kinase activity  protein binding  ATP binding  integral component of plasma membrane  signal transduction  mesoderm development  negative regulation of angiogenesis  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  negative regulation of cell migration  response to retinoic acid  plasma membrane fusion  
Ontology : EGO-EBIangiogenesis  vasculogenesis  in utero embryonic development  transmembrane receptor protein tyrosine kinase activity  protein binding  ATP binding  integral component of plasma membrane  signal transduction  mesoderm development  negative regulation of angiogenesis  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  negative regulation of cell migration  response to retinoic acid  plasma membrane fusion  
NDEx NetworkTIE1
Atlas of Cancer Signalling NetworkTIE1
Wikipedia pathwaysTIE1
Orthology - Evolution
OrthoDB7075
GeneTree (enSembl)ENSG00000066056
Phylogenetic Trees/Animal Genes : TreeFamTIE1
HOVERGENP35590
HOGENOMP35590
Homologs : HomoloGeneTIE1
Homology/Alignments : Family Browser (UCSC)TIE1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTIE1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TIE1
dbVarTIE1
ClinVarTIE1
1000_GenomesTIE1 
Exome Variant ServerTIE1
ExAC (Exome Aggregation Consortium)TIE1 (select the gene name)
Genetic variants : HAPMAP7075
Genomic Variants (DGV)TIE1 [DGVbeta]
DECIPHER (Syndromes)1:43766566-43788781  ENSG00000066056
CONAN: Copy Number AnalysisTIE1 
Mutations
ICGC Data PortalTIE1 
TCGA Data PortalTIE1 
Broad Tumor PortalTIE1
OASIS PortalTIE1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTIE1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTIE1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch TIE1
DgiDB (Drug Gene Interaction Database)TIE1
DoCM (Curated mutations)TIE1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TIE1 (select a term)
intoGenTIE1
NCG5 (London)TIE1
Cancer3DTIE1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600222   
Orphanet
MedgenTIE1
Genetic Testing Registry TIE1
NextProtP35590 [Medical]
TSGene7075
GENETestsTIE1
Huge Navigator TIE1 [HugePedia]
snp3D : Map Gene to Disease7075
BioCentury BCIQTIE1
ClinGenTIE1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD7075
Chemical/Pharm GKB GenePA36516
Clinical trialTIE1
Miscellaneous
canSAR (ICR)TIE1 (select the gene name)
Probes
Litterature
PubMed43 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
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