Overview
| Uniprot ID | Q02763 |
|---|
| Protein Name | Angiopoietin-1 receptor |
|---|
| Gene Name | TEK |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 858 |
DAAIKRMKEYASKDD |
Function
Tyrosine-protein kinase that acts as a cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of pro-inflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1
Protein Sequence
10
MDSLASLVLC
20
GVSLLLSGTV
30
EGAMDLILIN
40
SLPLVSDAET
50
SLTCIASGWR
60
PHEPITIGRD
70
FEALMNQHQD
80
PLEVTQDVTR
90
EWAKKVVWKR
100
EKASKINGAY
110
FCEGRVRGEA
120
IRIRTMKMRQ
130
QASFLPATLT
140
MTVDKGDNVN
150
ISFKKVLIKE
160
EDAVIYKNGS
170
FIHSVPRHEV
180
PDILEVHLPH
190
AQPQDAGVYS
200
ARYIGGNLFT
210
SAFTRLIVRR
220
CEAQKWGPEC
230
NHLCTACMNN
240
GVCHEDTGEC
250
ICPPGFMGRT
260
CEKACELHTF
270
GRTCKERCSG
280
QEGCKSYVFC
290
LPDPYGCSCA
300
TGWKGLQCNE
310
ACHPGFYGPD
320
CKLRCSCNNG
330
EMCDRFQGCL
340
CSPGWQGLQC
350
EREGIQRMTP
360
KIVDLPDHIE
370
VNSGKFNPIC
380
KASGWPLPTN
390
EEMTLVKPDG
400
TVLHPKDFNH
410
TDHFSVAIFT
420
IHRILPPDSG
430
VWVCSVNTVA
440
GMVEKPFNIS
450
VKVLPKPLNA
460
PNVIDTGHNF
470
AVINISSEPY
480
FGDGPIKSKK
490
LLYKPVNHYE
500
AWQHIQVTNE
510
IVTLNYLEPR
520
TEYELCVQLV
530
RRGEGGEGHP
540
GPVRRFTTAS
550
IGLPPPRGLN
560
LLPKSQTTLN
570
LTWQPIFPSS
580
EDDFYVEVER
590
RSVQKSDQQN
600
IKVPGNLTSV
610
LLNNLHPREQ
620
YVVRARVNTK
630
AQGEWSEDLT
640
AWTLSDILPP
650
QPENIKISNI
660
THSSAVISWT
670
ILDGYSISSI
680
TIRYKVQGKN
690
EDQHVDVKIK
700
NATITQYQLK
710
GLEPETAYQV
720
DIFAENNIGS
730
SNPAFSHELV
740
TLPESQAPAD
750
LGGGKMLLIA
760
ILGSAGMTCL
770
TVLLAFLIIL
780
QLKRANVQRR
790
MAQAFQNVRE
800
EPAVQFNSGT
810
LALNRKVKNN
820
PDPTIYPVLD
830
WNDIKFQDVI
840
GEGNFGQVLK
850
ARIKKDGLRM
860
DAAIKRMKEY
870
ASKDDHRDFA
880
GELEVLCKLG
890
HHPNIINLLG
900
ACEHRGYLYL
910
AIEYAPHGNL
920
LDFLRKSRVL
930
ETDPAFAIAN
940
STASTLSSQQ
950
LLHFAADVAR
960
GMDYLSQKQF
970
IHRDLAARNI
980
LVGENYVAKI
990
ADFGLSRGQE
1000
VYVKKTMGRL
1010
PVRWMAIESL
1020
NYSVYTTNSD
1030
VWSYGVLLWE
1040
IVSLGGTPYC
1050
GMTCAELYEK
1060
LPQGYRLEKP
1070
LNCDDEVYDL
1080
MRQCWREKPY
1090
ERPSFAQILV
1100
SLNRMLEERK
1110
TYVNTTLYEK
1120
FTYAGIDCSA
EEAA
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0016324 |
apical plasma membrane |
| Cellular Component |
GO:0009925 |
basal plasma membrane |
| Cellular Component |
GO:0016323 |
basolateral plasma membrane |
| Cellular Component |
GO:0009986 |
cell surface |
| Cellular Component |
GO:0005911 |
cell-cell junction |
| Cellular Component |
GO:0005856 |
cytoskeleton |
| Cellular Component |
GO:0005576 |
extracellular region |
| Cellular Component |
GO:0005925 |
focal adhesion |
| Cellular Component |
GO:0045121 |
membrane raft |
| Cellular Component |
GO:0005902 |
microvillus |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Cellular Component |
GO:0043235 |
receptor complex |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0042802 |
identical protein binding |
| Molecular Function |
GO:0004672 |
protein kinase activity |
| Molecular Function |
GO:0038023 |
signaling receptor activity |
| Molecular Function |
GO:0019199 |
transmembrane receptor protein kinase activity |
| Molecular Function |
GO:0004714 |
transmembrane receptor protein tyrosine kinase activity |
| Biological Process |
GO:0001525 |
angiogenesis |
| Biological Process |
GO:0007169 |
cell surface receptor protein tyrosine kinase signaling pathway |
| Biological Process |
GO:0007166 |
cell surface receptor signaling pathway |
| Biological Process |
GO:0007267 |
cell-cell signaling |
| Biological Process |
GO:0071260 |
cellular response to mechanical stimulus |
| Biological Process |
GO:0060216 |
definitive hemopoiesis |
| Biological Process |
GO:0001935 |
endothelial cell proliferation |
| Biological Process |
GO:0072012 |
glomerulus vasculature development |
| Biological Process |
GO:0007507 |
heart development |
| Biological Process |
GO:0060347 |
heart trabecula formation |
| Biological Process |
GO:0016525 |
negative regulation of angiogenesis |
| Biological Process |
GO:0043066 |
negative regulation of apoptotic process |
| Biological Process |
GO:2000352 |
negative regulation of endothelial cell apoptotic process |
| Biological Process |
GO:0050728 |
negative regulation of inflammatory response |
| Biological Process |
GO:0045766 |
positive regulation of angiogenesis |
| Biological Process |
GO:0010595 |
positive regulation of endothelial cell migration |
| Biological Process |
GO:0001938 |
positive regulation of endothelial cell proliferation |
| Biological Process |
GO:0070374 |
positive regulation of ERK1 and ERK2 cascade |
| Biological Process |
GO:0051894 |
positive regulation of focal adhesion assembly |
| Biological Process |
GO:1902533 |
positive regulation of intracellular signal transduction |
| Biological Process |
GO:0043410 |
positive regulation of MAPK cascade |
| Biological Process |
GO:0051897 |
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| Biological Process |
GO:0035022 |
positive regulation of Rac protein signal transduction |
| Biological Process |
GO:0035025 |
positive regulation of Rho protein signal transduction |
| Biological Process |
GO:2000351 |
regulation of endothelial cell apoptotic process |
| Biological Process |
GO:0032878 |
regulation of establishment or maintenance of cell polarity |
| Biological Process |
GO:0043114 |
regulation of vascular permeability |
| Biological Process |
GO:0002040 |
sprouting angiogenesis |
| Biological Process |
GO:0034446 |
substrate adhesion-dependent cell spreading |
| Biological Process |
GO:0048014 |
Tie signaling pathway |
Reference
[1] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.