TIE1

Summary

TIE1 (tyrosine kinase with immunoglobulin like and EGF like domains 1, HGNC:11809) is a protein-coding gene on chromosome 1p34.2, encoding Tyrosine-protein kinase receptor Tie-1 (P35590). Transmembrane tyrosine-protein kinase that may modulate TEK/TIE2 activity and contribute to the regulation of angiogenesis.

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.

Source: NCBI Gene 7075 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lymphatic malformation 11 (Strong, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 193 total — 1 pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 34 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11809
Approved symbol	TIE1
Name	tyrosine kinase with immunoglobulin like and EGF like domains 1
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	JTK14
Ensembl gene	ENSG00000066056
Ensembl biotype	protein_coding
OMIM	600222
Entrez	7075

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding_CDS_not_defined, 3 protein_coding, 1 nonsense_mediated_decay

ENST00000372476, ENST00000461061, ENST00000471187, ENST00000473014, ENST00000480269, ENST00000485125, ENST00000488437, ENST00000492599, ENST00000492874, ENST00000538015, ENST00000714825, ENST00000964802, ENST00000964803

RefSeq mRNA: 2 — MANE Select: NM_005424 NM_001253357, NM_005424

CCDS: CCDS482

Canonical transcript exons

ENST00000372476 — 23 exons

Exon	Start	End
ENSE00001045817	43312305	43312601
ENSE00001045821	43304851	43305165
ENSE00001457902	43322651	43323108
ENSE00001457922	43300982	43301129
ENSE00001616223	43305233	43305343
ENSE00001650032	43306840	43306995
ENSE00001668696	43317882	43318072
ENSE00001708753	43317564	43317674
ENSE00001734882	43307796	43307924
ENSE00001752414	43321396	43321492
ENSE00001754330	43317199	43317409
ENSE00001758715	43321616	43321715
ENSE00001760777	43319459	43319529
ENSE00001797345	43313135	43313425
ENSE00001803447	43321269	43321309
ENSE00003518611	43319235	43319348
ENSE00003524918	43311671	43311829
ENSE00003558009	43311994	43312131
ENSE00003585534	43307432	43307572
ENSE00003587560	43309388	43309532
ENSE00003597248	43308986	43309131
ENSE00003650789	43313778	43313968
ENSE00003661788	43307142	43307273

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 95.35.

FANTOM5 (CAGE): breadth broad, TPM avg 13.7123 / max 379.4397, expressed in 701 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2507	7.5188	529
2506	5.0223	624
2505	1.1712	367

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
omental fat pad	UBERON:0010414	95.35	gold quality
peritoneum	UBERON:0002358	95.25	gold quality
apex of heart	UBERON:0002098	95.06	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.64	gold quality
right lung	UBERON:0002167	93.97	gold quality
upper lobe of left lung	UBERON:0008952	93.66	gold quality
right lobe of thyroid gland	UBERON:0001119	93.31	gold quality
upper lobe of lung	UBERON:0008948	93.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.14	gold quality
left lobe of thyroid gland	UBERON:0001120	92.36	gold quality
body of uterus	UBERON:0009853	91.76	gold quality
thyroid gland	UBERON:0002046	90.92	gold quality
heart left ventricle	UBERON:0002084	90.88	gold quality
right atrium auricular region	UBERON:0006631	90.83	gold quality
tibial nerve	UBERON:0001323	90.62	gold quality
cardiac ventricle	UBERON:0002082	90.30	gold quality
adipose tissue	UBERON:0001013	90.12	gold quality
metanephros cortex	UBERON:0010533	90.12	gold quality
cardiac atrium	UBERON:0002081	89.75	gold quality
gall bladder	UBERON:0002110	89.03	gold quality
left uterine tube	UBERON:0001303	89.02	gold quality
connective tissue	UBERON:0002384	88.96	gold quality
spleen	UBERON:0002106	88.95	gold quality
heart	UBERON:0000948	88.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.71	gold quality
lower esophagus	UBERON:0013473	88.67	gold quality
lung	UBERON:0002048	88.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.80	gold quality
mucosa of stomach	UBERON:0001199	87.76	gold quality
gastrocnemius	UBERON:0001388	87.73	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	416.97
E-HCAD-10	yes	41.87
E-GEOD-134144	yes	38.67
E-MTAB-8410	yes	26.43
E-HCAD-1	yes	18.21
E-MTAB-6701	yes	15.75
E-ANND-3	yes	13.91
E-MTAB-6678	yes	13.32
E-CURD-46	yes	12.07
E-CURD-112	yes	8.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF2, GATA4, KLF11, RARG, RUNX1

miRNA regulators (miRDB)

24 targeting TIE1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-4460	99.37	68.52	615
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255
HSA-MIR-194-3P	97.36	65.96	1027
HSA-MIR-27B-5P	97.34	66.55	549
HSA-MIR-6874-5P	95.73	64.94	545

Literature-anchored findings (GeneRIF, showing 31)

• Vascular endothelial growth factor modulates the Tie-2:Tie-1 receptor complex (PMID:11866538)
• high expression independently associated with shorter survival in patients with early chronic phase CML (PMID:11920509)
• Results describe the expression of angiopoietin-1, 2 and 4 and Tie-1 and 2 in gastrointestinal stromal tumors, leiomyomas and schwannomas. (PMID:17724803)
• Activation of Tie1 ectodomain cleavage increases cartilage oligomeric protein angiopoietin 1 activation of Tie2. (PMID:17728252)
• Overexpression and activation of Tie1 is associated with breast and colonic neopalsms (PMID:17786322)
• the trophoblastic shell of the very early human placenta, as well as endothelial cells and ACC exhibited strong staining intensity for Tie-1 (PMID:18675456)
• Tie-1 has an inflammatory function in endothelial cells. (PMID:19236867)
• A natural antisense transcript was identified for tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 (tie-1), tie-1AS long noncoding RNA in zebrafish, mouse, and humans. (PMID:19880500)
• The Tie-1 immunoreactivity was dominantly observed in the heamangiogenic cells and cells cords, whereas the matured villi showed immunoreactivity only in other components. (PMID:20164029)
• Provide evidence for Tie1-Tie2 complex formation on the cell surface and identify molecular surface areas essential for recognition. The Tie1-Tie2 interactions are dynamic, inhibitory, and differentially modulated by angiopoietin-1 and -2. (PMID:20227369)
• the effects of factors activating ectodomain cleavage on both Tie1 and Tie2 within the same population of cells, and their impact on angiopoietin signalling (PMID:22235284)
• these results suggest that the expression level of Tie1 and its physical interaction with Tie2 defines whether Ang2 functions as a Tie2 agonist or antagonist, thereby determining the context-dependent differential endothelial sensitivity to Ang2. (PMID:22342979)
• Data propose that EndMT associated with Tie1 downregulation participates in the pathological development of stroma observed in tumours. (PMID:22421998)
• The decreasing expression of Tie1 may play an important role in the pathogenesis of primary lower extremity varicose veins. (PMID:22987233)
• T794A-expressing human umbilical vein endothelial cells formed significantly shorter tubes with fewer branches in three-dimensional Matrigel cultures, but did not alter Tie1 or Tie2 tyrosine phosphorylation or downstream signaling. (PMID:26436659)
• The inhibition of Tie-2 exerted by Tie-1can be relieved by Tie-1 ectodomain cleavage mediated by tumor- and inflammatory-related factors, which causes destabilization of vessels and initiates vessel remodeling in cancer. (Review) (PMID:26489611)
• Tie1 directly interacts with Tie2 to promote ANG-induced vascular responses under noninflammatory conditions, whereas in inflammation, Tie1 cleavage contributes to loss of ANG2 agonist activity and vascular stability (PMID:27548530)
• In vitro binding assays with purified components reveal that Tie-integrin recognition is direct, and further demonstrate that the receptor binding domain of the Tie2 ligand Ang-1, but not the receptor binding domain of Ang-2, can independently associate with a5b1 or aVb3. cooperative Tie/integrin interactions selectively stimulate ERK/MAPK signaling in the presence of both Ang-1 and fibronectin (PMID:27695111)
• Ang,Tie1 and Tie2 play roles in vascular development and pathogenesis of vascular diseases.[review] (PMID:27941161)
• We identified colorectal cancer as a novel Tie1-expressing tumor, with Tie1-positive cells hardly detectable in the normal intestine. Tie1 expression did not influence cancer cell proliferation in regular in vitro cultures, but significantly affected malignant growth of transplanted tumors in vivo. (PMID:28464467)
• Tie1 has regulatory functions in angiogenesis and vascular abnormalization as well as metastasis (PMID:29355844)
• Results found deregulated expression of TIE1 in non-small cell lung cancer (NSCLC) tissues to be associated with poor clinical outcome. (PMID:30806032)
• Study in metastatic breast cancer patients treated with a taxane-bevacizumab combination chemotherapy revealed that overall and progression-free survival was significantly shorter in patients with a high baseline Tie1 level demonstrating the prognostic value of baseline Tie1 plasma concentration in patients with metastatic breast cancer. (PMID:31340773)
• TIE1 as a Candidate Gene for Lymphatic Malformations with or without Lymphedema. (PMID:32947856)
• Involvement of small extracellular vesicle-derived TIE-1 in the chemoresistance of ovarian cancer cells. (PMID:33812182)
• A novel cis-regulatory variant modulating TIE1 expression associated with attention deficit hyperactivity disorder in Han Chinese children. (PMID:34942230)
• FLI1 regulates radiotherapy resistance in nasopharyngeal carcinoma through TIE1-mediated PI3K/AKT signaling pathway. (PMID:36814284)
• Possible biallelic inheritance in TIE1 in a family with congenital lymphedema, intestinal lymphangiectasia and cutis aplasia. (PMID:37096293)
• Cerebrospinal Fluid C1-Esterase Inhibitor and Tie-1 Levels Affect Cognitive Performance: Evidence from Proteome-Wide Mendelian Randomization. (PMID:38254961)
• TIE1 promotes cervical cancer progression via Basigin-matrix metalloproteinase axis. (PMID:38617545)
• Loss-of-function mutations of the TIE1 receptor tyrosine kinase cause late-onset primary lymphedema. (PMID:38820174)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tie1	ENSDARG00000004105
mus_musculus	Tie1	ENSMUSG00000033191
rattus_norvegicus	Tie1	ENSRNOG00000020173

Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715)

Protein

Protein identifiers

Tyrosine-protein kinase receptor Tie-1 — P35590 (reviewed: P35590)

All UniProt accessions (2): P35590, A0AAQ5BI97

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Heterodimer with TEK/TIE2. Interacts with SVEP1 (via C-terminus).

Subcellular location. Cell membrane.

Tissue specificity. Specifically expressed in developing vascular endothelial cells.

Post-translational modifications. Phosphorylated on tyrosine residues in response to ANGPT1, most likely by TEK/TIE2.

Disease relevance. Lymphatic malformation 11 (LMPHM11) [MIM:619401] A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM11 is an autosomal dominant form characterized by onset of lower extremity edema in the second or third decade of life. Some affected individuals may have subclinical lymphatic malformations. The disease may be caused by variants affecting the gene represented in this entry.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P35590-1	1	yes
P35590-2	2
P35590-3	3

RefSeq proteins (2): NP_001240286, NP_005415* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000742	EGF	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050122	RTK	Family

Pfam: PF00041, PF00047, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0011–0.129	4
AC-DYFE-6-CHLORO-W-NHME	0.0051	1
AC-DYFGW-NHME	0.07	1
YFEW	0.232	1

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (44 total): domain 9, disulfide bond 6, strand 6, glycosylation site 5, sequence variant 5, splice variant 4, binding site 2, topological domain 2, signal peptide 1, chain 1, active site 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5N06	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35590-F1	81.14	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 979 (proton acceptor)

Ligand- & substrate-binding residues (2): 845–853; 870

Post-translational modifications (1): 1007

Disulfide bonds (6): 228–237, 231–244, 246–255, 315–327, 321–333, 335–344

Glycosylation sites (5): 83, 161, 503, 596, 709

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 225 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, MORF_FLT1, MODULE_418, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_MEMBRANE_FUSION, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_EXTRACELLULAR_MATRIX_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ASSEMBLY, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP

GO Biological Process (20): angiogenesis (GO:0001525), vasculogenesis (GO:0001570), in utero embryonic development (GO:0001701), regulation of endothelial cell proliferation (GO:0001936), aortic valve morphogenesis (GO:0003180), signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), mesoderm development (GO:0007498), negative regulation of angiogenesis (GO:0016525), negative regulation of cell migration (GO:0030336), response to retinoic acid (GO:0032526), obsolete plasma membrane fusion (GO:0045026), positive regulation of angiogenesis (GO:0045766), tissue remodeling (GO:0048771), lymphatic endothelial cell differentiation (GO:0060836), branching involved in lymph vessel morphogenesis (GO:0060854), regulation of extracellular matrix assembly (GO:1901201), blood vessel development (GO:0001568), protein phosphorylation (GO:0006468), tissue development (GO:0009888)

GO Molecular Function (8): transmembrane receptor protein tyrosine kinase activity (GO:0004714), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood vessel morphogenesis	2
angiogenesis	2
regulation of angiogenesis	2
anatomical structure development	2
anatomical structure formation involved in morphogenesis	1
cell differentiation	1
chordate embryonic development	1
endothelial cell proliferation	1
regulation of epithelial cell proliferation	1
aortic valve development	1
heart valve morphogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
tissue development	1
negative regulation of blood vessel morphogenesis	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
response to lipid	1
response to oxygen-containing compound	1
positive regulation of vasculature development	1
multicellular organismal process	1
lymph vessel development	1
endothelial cell differentiation	1
lymphangiogenesis	1
lymph vessel morphogenesis	1
branching morphogenesis of an epithelial tube	1
regulation of cellular component biogenesis	1
extracellular matrix assembly	1
regulation of extracellular matrix organization	1
vasculature development	1
phosphorylation	1
protein modification process	1
protein tyrosine kinase activity	1
transmembrane receptor protein kinase activity	1
adenyl ribonucleotide binding	1

Protein interactions and networks

STRING

1306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TIE1	ANGPT1	Q15389	998
TIE1	ANGPT2	O15123	992
TIE1	ANGPT4	Q9Y264	942
TIE1	ANGPTL2	Q9UKU9	819
TIE1	ANGPTL3	Q9Y5C1	763
TIE1	VEGFC	P49767	755
TIE1	LECT2	O14960	752
TIE1	NGF	P01138	720
TIE1	VPS51	Q9UID3	711
TIE1	PGF	P49763	705
TIE1	ANGPTL1	O95841	700
TIE1	PTPRB	P23467	690
TIE1	CDH5	P33151	687
TIE1	EGF	P01133	673
TIE1	FGF2	P09038	655

IntAct

36 interactions, top by confidence:

A	B	Type	Score
TIE1	NTRK1	psi-mi:“MI:0915”(physical association)	0.590
NTRK1	TIE1	psi-mi:“MI:0407”(direct interaction)	0.590
NTRK1	TIE1	psi-mi:“MI:0403”(colocalization)	0.590
KRT40	TIE1	psi-mi:“MI:0915”(physical association)	0.560
RBPMS	TIE1	psi-mi:“MI:0915”(physical association)	0.560
TIE1	KRT40	psi-mi:“MI:0915”(physical association)	0.560
TIE1	RBPMS	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	TIE1	psi-mi:“MI:0915”(physical association)	0.560
TIE1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
TIE1	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
PSG5	TIE1	psi-mi:“MI:0915”(physical association)	0.540
PSG5	TIE1	psi-mi:“MI:0407”(direct interaction)	0.540
TIE1	PSG5	psi-mi:“MI:0407”(direct interaction)	0.540
TIE1	MDFI	psi-mi:“MI:0915”(physical association)	0.490
ANGPT1	TIE1	psi-mi:“MI:0407”(direct interaction)	0.440
Dlg4	TIE1	psi-mi:“MI:0407”(direct interaction)	0.440
TIE1	HNRNPF	psi-mi:“MI:0915”(physical association)	0.400
TIE1	MOG	psi-mi:“MI:0915”(physical association)	0.400
TIE1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
CDC37	TIE1	psi-mi:“MI:0915”(physical association)	0.400
MTMR14	TIE1	psi-mi:“MI:0915”(physical association)	0.370
EZR	MACROD2	psi-mi:“MI:0914”(association)	0.350
TIE1	Msn	psi-mi:“MI:0914”(association)	0.350
TIE1	TRIP6	psi-mi:“MI:0915”(physical association)	0.000
PTPRC	TIE1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRG	TIE1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000
PTPRJ	TIE1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.000

BioGRID (16): RBPMS (Two-hybrid), KRT40 (Two-hybrid), MTMR14 (Two-hybrid), TIE1 (Protein-peptide), TIE1 (Affinity Capture-MS), TIE1 (Two-hybrid), TRIP6 (Two-hybrid), KRTAP10-8 (Two-hybrid), HNRNPF (Proximity Label-MS), ANGPT4 (Reconstituted Complex), TEK (Affinity Capture-Western), TIE1 (Cross-Linking-MS (XL-MS)), TIE1 (Dosage Lethality), TIE1 (Affinity Capture-Luminescence), MDFI (Two-hybrid)

ESM2 similar proteins: A0A0U1RPR8, O02740, O08644, O09127, O15197, O19179, O73875, O73878, P0C0K6, P0C0K7, P14616, P16067, P20594, P21709, P26770, P29317, P29322, P35590, P46197, P51839, P51840, P51841, P51842, P52333, P52785, P54753, P54754, P54760, P54761, P55203, P55205, Q02846, Q03146, Q06805, Q06806, Q08345, Q1KL86, Q5JZY3, Q5SDA5, Q60750

Diamond homologs: A0JM20, A0M8R7, A0M8S8, A1X150, F1QVU0, G3V9H8, O02466, O35346, P00519, P00520, P00521, P00522, P00529, P06213, P07949, P08069, P08581, P08941, P09760, P0DV84, P10447, P13368, P14617, P16056, P20806, P22182, P23049, P30530, P33497, P34152, P34925, P35546, P35590, P42684, P55144, P55146, P57097, P70451, P97523, P97793

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ANGPT1	up-regulates	TIE1	binding
TEK	“up-regulates activity”	TIE1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

193 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	165
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1174132	NM_005424.5(TIE1):c.1441C>T (p.Arg481Cys)	Pathogenic

SpliceAI

3474 predictions. Top by Δscore:

Variant	Effect	Δscore
1:43305164:AGGT:A	donor_loss	1.0000
1:43305165:GGT:G	donor_loss	1.0000
1:43305167:T:G	donor_loss	1.0000
1:43305231:A:AG	acceptor_gain	1.0000
1:43305232:G:GG	acceptor_gain	1.0000
1:43305232:GCCC:G	acceptor_gain	1.0000
1:43305340:AACGG:A	donor_loss	1.0000
1:43305341:ACGGT:A	donor_loss	1.0000
1:43305344:G:GA	donor_loss	1.0000
1:43305345:T:A	donor_loss	1.0000
1:43306950:G:GT	donor_gain	1.0000
1:43306950:G:T	donor_gain	1.0000
1:43307003:G:GT	donor_gain	1.0000
1:43309102:C:G	donor_gain	1.0000
1:43309386:A:AG	acceptor_gain	1.0000
1:43309387:G:GT	acceptor_gain	1.0000
1:43309387:GT:G	acceptor_gain	1.0000
1:43309387:GTC:G	acceptor_gain	1.0000
1:43309387:GTCC:G	acceptor_gain	1.0000
1:43309387:GTCCA:G	acceptor_gain	1.0000
1:43309529:AAAG:A	donor_gain	1.0000
1:43309531:AGGT:A	donor_loss	1.0000
1:43309532:GGTC:G	donor_loss	1.0000
1:43309533:G:A	donor_loss	1.0000
1:43309534:T:A	donor_loss	1.0000
1:43311826:GTGG:G	donor_gain	1.0000
1:43311828:GG:G	donor_gain	1.0000
1:43311829:GG:G	donor_gain	1.0000
1:43313403:AGAAG:A	donor_gain	1.0000
1:43317563:GA:G	acceptor_gain	1.0000

AlphaMissense

7328 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:43317337:T:C	F850L	1.000
1:43317339:C:A	F850L	1.000
1:43317339:C:G	F850L	1.000
1:43317924:T:C	L925P	1.000
1:43317936:T:C	L929P	1.000
1:43318017:T:C	L956P	1.000
1:43318046:G:C	G966R	1.000
1:43318047:G:A	G966D	1.000
1:43319241:C:G	H977D	1.000
1:43319242:A:G	H977R	1.000
1:43319245:G:C	R978T	1.000
1:43319245:G:T	R978M	1.000
1:43319246:G:C	R978S	1.000
1:43319246:G:T	R978S	1.000
1:43319247:G:C	D979H	1.000
1:43319248:A:C	D979A	1.000
1:43319248:A:G	D979G	1.000
1:43319248:A:T	D979V	1.000
1:43319249:C:A	D979E	1.000
1:43319249:C:G	D979E	1.000
1:43319251:T:C	L980P	1.000
1:43319254:C:A	A981D	1.000
1:43319257:C:A	A982D	1.000
1:43319260:G:C	R983P	1.000
1:43319260:G:T	R983L	1.000
1:43319262:A:G	N984D	1.000
1:43319264:T:A	N984K	1.000
1:43319264:T:G	N984K	1.000
1:43319301:G:C	D997H	1.000
1:43319302:A:C	D997A	1.000

dbSNP variants (sampled 300 via entrez): RS1000008078 (1:43310288 G>T), RS1000042253 (1:43303521 C>T), RS1000089908 (1:43323427 C>G), RS1000254972 (1:43304583 G>A), RS1000459608 (1:43318598 G>A), RS1000461711 (1:43305064 G>C), RS1000490499 (1:43318318 G>A), RS1000782220 (1:43323503 ACTGT>A), RS1000972456 (1:43310958 G>A), RS1001066309 (1:43317308 C>T), RS1001321344 (1:43299235 TC>T), RS1001364931 (1:43317004 T>C), RS1001576420 (1:43299894 G>A,C), RS1001805490 (1:43298995 A>G), RS1001959682 (1:43305760 G>C)

Disease associations

OMIM: gene MIM:600222 | disease phenotypes: MIM:619401

GenCC curated gene-disease

Disease	Classification	Inheritance
lymphatic malformation 11	Strong	Autosomal dominant

Mondo (1): lymphatic malformation 11 (MONDO:0030316)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001004	Lymphedema
HP:0003621	Juvenile onset
HP:0010741	Pedal edema
HP:0011462	Young adult onset

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST006585_190	Blood protein levels	5.000000e-16
GCST010083_216	Hemoglobin levels	1.000000e-10
GCST010696_6	Cortical thickness (min-P)	3.000000e-08
GCST010697_32	Cortical surface area (min-P)	4.000000e-08
GCST010698_63	Subcortical volume (min-P)	3.000000e-09
GCST010699_87	Brain morphology (min-P)	9.000000e-14
GCST010700_24	Cortical thickness (MOSTest)	1.000000e-10
GCST010701_5	Cortical surface area (MOSTest)	1.000000e-08
GCST010702_132	Subcortical volume (MOSTest)	8.000000e-15
GCST010703_201	Brain morphology (MOSTest)	1.000000e-11
GCST90002402_545	Platelet count	8.000000e-28
GCST90002403_44	Red blood cell count	8.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004309	platelet count
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5274 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

34 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 473,132 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL377300	BRIVANIB	3	1,721
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL475251	R-406	2
CHEMBL5083772	BIIB-091	2
CHEMBL558752	RAF-265	2
CHEMBL572878	TOZASERTIB	2
CHEMBL575448	BMS-754807	2
CHEMBL607707	PELITINIB	2

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type XII RTKs: TIE family of angiopoietin receptors

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 6li [Chan et al., 2022]	Inhibition	9.13	pKd
merestinib	Inhibition	9.05	pKd
BIIB091	Inhibition	7.4	pKd

Binding affinities (BindingDB)

17 measured of 17 human assays (17 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
Staurosporine	KD	1.7 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
PKC-412	KD	190 nM
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
ERLOTINIB HYDROCHLORIDE	KD	1200 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}-N-(3-fluorophenyl)acetamide	KD	1900 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	KD	4500 nM

ChEMBL bioactivities

79 potent at pChembl≥5 of 79 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.54	Kd	0.29	nM	AST-487
9.13	Kd	0.74	nM	CHEMBL5197792
9.10	Kd	0.79	nM	FORETINIB
9.05	Kd	0.9	nM	BAY-826
8.27	IC50	5.4	nM	BAY-826
8.08	Kd	8.3	nM	DORAMAPIMOD
7.96	EC50	11	nM	BAY-826
7.82	Kd	15	nM	TAE-684
7.40	Kd	40	nM	BIIB-091
7.19	Kd	65	nM	STAUROSPORINE
7.17	Kd	67	nM	CHEMBL5415503
7.17	Kd	68	nM	SORAFENIB
7.12	Kd	76	nM	R-406
7.01	Kd	97	nM	AXITINIB
6.96	Kd	110	nM	LINIFANIB
6.96	Kd	110	nM	CRIZOTINIB
6.89	IC50	130	nM	BAY-309
6.82	Kd	150	nM	RAF-265
6.58	Kd	260	nM	JNJ-7706621
6.57	Kd	270	nM	TOZASERTIB
6.54	Kd	290	nM	CEDIRANIB
6.52	Kd	300	nM	KW-2449
6.46	Kd	350	nM	DEFOSBARASERTIB
6.41	Kd	390	nM	NERATINIB
6.22	Kd	600	nM	BMS-754807
6.17	Kd	680	nM	LESTAURTINIB
6.16	Kd	700	nM	PAZOPANIB
6.16	Kd	700	nM	FEDRATINIB
6.11	Kd	770	nM	CHEMBL4792981
6.07	Kd	850	nM	ERLOTINIB
6.00	Kd	1000	nM	PELITINIB
6.00	Kd	1000	nM	NILOTINIB
5.96	Kd	1100	nM	BRIVANIB
5.92	Kd	1200	nM	CHEMBL386051
5.92	Kd	1200	nM	PHA-665752
5.85	Kd	1400	nM	MIDOSTAURIN
5.85	Kd	1400	nM	GSK-461364
5.82	Kd	1500	nM	VANDETANIB
5.80	Kd	1600	nM	MLN-8054
5.66	Kd	2200	nM	CANERTINIB
5.66	Kd	2200	nM	NINTEDANIB
5.60	IC50	2500	nM	CHEMBL169390
5.58	EC50	2600	nM	BAY-309
5.54	Kd	2900	nM	BOSUTINIB
5.50	Kd	3200	nM	QUIZARTINIB
5.43	Kd	3700	nM	QUIZARTINIB
5.41	Kd	3900	nM	SUNITINIB
5.40	Kd	4000	nM	DOVITINIB
5.37	IC50	4300	nM	CHEMBL3582441
5.36	IC50	4400	nM	CHEMBL4858720

PubChem BioAssay actives

69 with measured affinity, of 197 total; 49 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435198: Binding constant for TIE1 kinase domain	kd	0.0003	uM
N-cyclohexyl-3-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyanilino]-1-methylpyrazole-4-carboxamide	1849358: Binding affinity to TIE1 (unknown origin) assessed as dissociation constant by competition binding assay	kd	0.0007	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625017: Binding constant for TIE1 kinase domain	kd	0.0008	uM
3-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[2,1-e]pyrazol-1-yl)phenyl]-5-(pentafluoro-lambda6-sulfanyl)benzamide	2155083: Binding affinity to TIE1 (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0009	uM
1-[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	435198: Binding constant for TIE1 kinase domain	kd	0.0083	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	625017: Binding constant for TIE1 kinase domain	kd	0.0150	uM
1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(oxetan-3-yl)-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide	1820537: Binding affinity to wild-type human partial length TIE1 (T819 to A1138 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0400	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	435198: Binding constant for TIE1 kinase domain	kd	0.0650	uM
N-[3-[2-[2-ethoxy-4-(4-methylpiperazin-1-yl)anilino]-7-oxo-8-[[(2R)-oxolan-2-yl]methyl]pyrido[2,3-d]pyrimidin-6-yl]phenyl]-3-(trifluoromethyl)benzamide	1988554: Binding affinity to TIE1 (unknown origin) assessed as dissociation constant by KINOME scan assay	kd	0.0670	uM
Sorafenib	435198: Binding constant for TIE1 kinase domain	kd	0.0680	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625017: Binding constant for TIE1 kinase domain	kd	0.0760	uM
Axitinib	625017: Binding constant for TIE1 kinase domain	kd	0.0970	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	435198: Binding constant for TIE1 kinase domain	kd	0.1100	uM
Crizotinib	625017: Binding constant for TIE1 kinase domain	kd	0.1100	uM
1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	435198: Binding constant for TIE1 kinase domain	kd	0.1500	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435198: Binding constant for TIE1 kinase domain	kd	0.2600	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435198: Binding constant for TIE1 kinase domain	kd	0.2700	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	625017: Binding constant for TIE1 kinase domain	kd	0.2900	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625017: Binding constant for TIE1 kinase domain	kd	0.3000	uM
2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide	435198: Binding constant for TIE1 kinase domain	kd	0.3500	uM
Neratinib	625017: Binding constant for TIE1 kinase domain	kd	0.3900	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide	2167405: Binding affinity to TIE1 (unknown origin) by phage based competition assay	kd	0.6000	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508109: Binding affinity to TIE1	kd	0.6800	uM
Pazopanib	435198: Binding constant for TIE1 kinase domain	kd	0.7000	uM
Fedratinib	625017: Binding constant for TIE1 kinase domain	kd	0.7000	uM
N-[(1R)-1-(3,5-difluorophenyl)ethyl]-3-[(E)-2-pyridin-2-ylethenyl]-2H-indazol-5-amine	1741261: Binding affinity to wild-type human partial length TIE1 (T819 to A1138 residues) expressed in bacterial expression system by Kinomescan method relative to control	kd	0.7700	uM
Erlotinib	435198: Binding constant for TIE1 kinase domain	kd	0.8500	uM
Nilotinib	625017: Binding constant for TIE1 kinase domain	kd	1.0000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	435198: Binding constant for TIE1 kinase domain	kd	1.0000	uM
(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-ol	625017: Binding constant for TIE1 kinase domain	kd	1.1000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	625017: Binding constant for TIE1 kinase domain	kd	1.2000	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625017: Binding constant for TIE1 kinase domain	kd	1.2000	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	625017: Binding constant for TIE1 kinase domain	kd	1.4000	uM
Midostaurin	435198: Binding constant for TIE1 kinase domain	kd	1.4000	uM
Vandetanib	435198: Binding constant for TIE1 kinase domain	kd	1.5000	uM
4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	435198: Binding constant for TIE1 kinase domain	kd	1.6000	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625017: Binding constant for TIE1 kinase domain	kd	2.2000	uM
N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide	435198: Binding constant for TIE1 kinase domain	kd	2.2000	uM
3-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)phenol	1774907: Inhibition of TIE1 (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 48 hrs by cell proliferation assay	ic50	2.5000	uM
Bosutinib	625017: Binding constant for TIE1 kinase domain	kd	2.9000	uM
Quizartinib	508109: Binding affinity to TIE1	kd	3.2000	uM
Sunitinib	625017: Binding constant for TIE1 kinase domain	kd	3.9000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435198: Binding constant for TIE1 kinase domain	kd	4.0000	uM
2-[4-[4-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]-2-pyridinyl]piperazin-1-yl]acetic acid	1229370: Inhibition of Tel-fused TIE1 (unknown origin) expressed in mouse BA/F3 cells after 48 hrs by luciferase reporter gene assay in absence of recombinant mouse IL3	ic50	4.3000	uM
3-[4-amino-7-[3-(hydroxymethyl)cyclobutyl]pyrrolo[2,3-d]pyrimidin-5-yl]phenol	1774907: Inhibition of TIE1 (unknown origin) expressed in mouse BaF3 cells assessed as reduction in cell proliferation incubated for 48 hrs by cell proliferation assay	ic50	4.4000	uM
4-[6-(benzylamino)imidazo[1,2-b]pyridazin-3-yl]benzonitrile	1229370: Inhibition of Tel-fused TIE1 (unknown origin) expressed in mouse BA/F3 cells after 48 hrs by luciferase reporter gene assay in absence of recombinant mouse IL3	ic50	5.5000	uM
1-[4-[6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]imidazo[1,2-b]pyridazin-3-yl]-2-pyridinyl]piperidin-4-ol	1229370: Inhibition of Tel-fused TIE1 (unknown origin) expressed in mouse BA/F3 cells after 48 hrs by luciferase reporter gene assay in absence of recombinant mouse IL3	ic50	5.5000	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	625017: Binding constant for TIE1 kinase domain	kd	5.7000	uM
6-[(2R)-2-(3-fluorophenyl)pyrrolidin-1-yl]-3-pyridin-2-ylimidazo[1,2-b]pyridazine	1229370: Inhibition of Tel-fused TIE1 (unknown origin) expressed in mouse BA/F3 cells after 48 hrs by luciferase reporter gene assay in absence of recombinant mouse IL3	ic50	6.5000	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	increases methylation, affects methylation	2
bisphenol A	affects expression	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
entinostat	increases expression	1
beta-hydroxy simvastatin acid	decreases expression	1
Decitabine	affects expression	1
Atrazine	increases expression	1
Cisplatin	affects expression	1
DDT	decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects expression	1
Formaldehyde	decreases expression	1
Parathion	increases methylation	1
Tamoxifen	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	increases methylation	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1
tert-Butylhydroperoxide	increases expression	1

ChEMBL screening assays

96 unique, capped per target: 96 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1059377	Binding	Inhibition of TIE1 assessed as enzyme activity at 1 uM relative to untreated control	Selective inhibitors of the mutant B-Raf pathway: discovery of a potent and orally bioavailable aminoisoquinoline. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.