UniProtKB - Q15389 (ANGP1_HUMAN)
Protein
Angiopoietin-1
Gene
ANGPT1
Organism
Homo sapiens (Human)
Status
Functioni
Binds and activates TEK/TIE2 receptor by inducing its dimerization and tyrosine phosphorylation. Plays an important role in the regulation of angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Required for normal angiogenesis and heart development during embryogenesis. 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. Mediates blood vessel maturation/stability. Implicated in endothelial developmental processes later and distinct from that of VEGF. Appears to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme.4 Publications
Miscellaneous
It may have a potential therapeutic utility since it can be used for specifically targeting tumor vasculature or for promoting angiogenic processes in certain organs such as an ischemic heart.
GO - Molecular functioni
- receptor tyrosine kinase binding Source: UniProtKB
- signaling receptor binding Source: GO_Central
GO - Biological processi
- activation of transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
- angiogenesis Source: GO_Central
- cell differentiation Source: UniProtKB-KW
- cell-substrate adhesion Source: Ensembl
- glomerulus vasculature development Source: UniProtKB
- hemopoiesis Source: Ensembl
- heparin biosynthetic process Source: UniProtKB
- in utero embryonic development Source: Ensembl
- leukocyte migration Source: Reactome
- MAPK cascade Source: Reactome
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of cell adhesion Source: UniProtKB
- negative regulation of cytokine production involved in immune response Source: Ensembl
- negative regulation of endothelial cell apoptotic process Source: UniProtKB
- negative regulation of neuron apoptotic process Source: Ensembl
- negative regulation of protein import into nucleus Source: Ensembl
- negative regulation of protein phosphorylation Source: Ensembl
- negative regulation of vascular permeability Source: UniProtKB
- positive chemotaxis Source: UniProtKB
- positive regulation of blood-brain barrier permeability Source: ARUK-UCL
- positive regulation of blood vessel endothelial cell migration Source: UniProtKB
- positive regulation of cell adhesion Source: Ensembl
- positive regulation of endothelial cell migration Source: UniProtKB
- positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
- positive regulation of gene expression Source: ARUK-UCL
- positive regulation of peptidyl-serine phosphorylation Source: Ensembl
- positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
- positive regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
- positive regulation of protein kinase B signaling Source: UniProtKB
- positive regulation of protein phosphorylation Source: ARUK-UCL
- positive regulation of protein ubiquitination Source: UniProtKB
- positive regulation of receptor internalization Source: UniProtKB
- protein localization to cell surface Source: UniProtKB
- regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
- regulation of macrophage migration inhibitory factor signaling pathway Source: Ensembl
- regulation of protein binding Source: Ensembl
- regulation of skeletal muscle satellite cell proliferation Source: UniProtKB
- regulation of tumor necrosis factor production Source: Ensembl
- sprouting angiogenesis Source: UniProtKB
- Tie signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Developmental protein |
Biological process | Angiogenesis, Differentiation |
Enzyme and pathway databases
PathwayCommonsi | Q15389 |
Reactomei | R-HSA-210993, Tie2 Signaling R-HSA-5673001, RAF/MAP kinase cascade |
SignaLinki | Q15389 |
SIGNORi | Q15389 |
Names & Taxonomyi
Protein namesi | Recommended name: Angiopoietin-1Short name: ANG-1 |
Gene namesi | Name:ANGPT1 Synonyms:KIAA0003 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:484, ANGPT1 |
MIMi | 601667, gene |
neXtProti | NX_Q15389 |
VEuPathDBi | HostDB:ENSG00000154188.9 |
Subcellular locationi
Extracellular region or secreted
Extracellular region or secreted
- collagen-containing extracellular matrix Source: GO_Central
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- membrane raft Source: UniProtKB
- microvillus Source: UniProtKB
Keywords - Cellular componenti
SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 284 |
MalaCardsi | ANGPT1 |
OpenTargetsi | ENSG00000154188 |
Orphaneti | 537891, ANGPT1-related hereditary angioedema with normal C1Inh |
PharmGKBi | PA24791 |
Miscellaneous databases
Pharosi | Q15389, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3217395 |
Genetic variation databases
BioMutai | ANGPT1 |
DMDMi | 12229574 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 15 | Sequence analysisAdd BLAST | 15 | |
ChainiPRO_0000009110 | 16 – 498 | Angiopoietin-1Add BLAST | 483 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 92 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 122 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 154 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 243 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 286 ↔ 315 | PROSITE-ProRule annotation | ||
Glycosylationi | 295 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 439 ↔ 452 | PROSITE-ProRule annotation |
Post-translational modificationi
Glycosylated.
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | Q15389 |
MassIVEi | Q15389 |
PaxDbi | Q15389 |
PeptideAtlasi | Q15389 |
PRIDEi | Q15389 |
ProteomicsDBi | 60559 [Q15389-1] |
PTM databases
GlyGeni | Q15389, 5 sites |
iPTMneti | Q15389 |
PhosphoSitePlusi | Q15389 |
Expressioni
Gene expression databases
Bgeei | ENSG00000154188, Expressed in cauda epididymis and 205 other tissues |
ExpressionAtlasi | Q15389, baseline and differential |
Genevisiblei | Q15389, HS |
Organism-specific databases
HPAi | ENSG00000154188, Low tissue specificity |
Interactioni
Subunit structurei
Homooligomer.
Interacts with TEK/TIE2.
3 PublicationsBinary interactionsi
Isoform 2 [Q15389-2]
With | #Exp. | IntAct |
---|---|---|
MAPK8IP2 [Q13387] | 3 | EBI-10692491,EBI-722813 |
GO - Molecular functioni
- receptor tyrosine kinase binding Source: UniProtKB
- signaling receptor binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 106781, 4 interactors |
IntActi | Q15389, 3 interactors |
MINTi | Q15389 |
STRINGi | 9606.ENSP00000428340 |
Miscellaneous databases
RNActi | Q15389, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q15389 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 277 – 497 | Fibrinogen C-terminalPROSITE-ProRule annotationAdd BLAST | 221 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 81 – 119 | Sequence analysisAdd BLAST | 39 | |
Coiled coili | 153 – 261 | Sequence analysisAdd BLAST | 109 |
Keywords - Domaini
Coiled coil, SignalPhylogenomic databases
eggNOGi | KOG2579, Eukaryota |
GeneTreei | ENSGT00940000158117 |
HOGENOMi | CLU_038628_3_1_1 |
InParanoidi | Q15389 |
OMAi | EHRILEM |
OrthoDBi | 357340at2759 |
PhylomeDBi | Q15389 |
TreeFami | TF336658 |
Family and domain databases
CDDi | cd00087, FReD, 1 hit |
Gene3Di | 3.90.215.10, 1 hit 4.10.530.10, 1 hit |
InterProi | View protein in InterPro IPR028843, Ang-1 IPR036056, Fibrinogen-like_C IPR014716, Fibrinogen_a/b/g_C_1 IPR014715, Fibrinogen_a/b/g_C_2 IPR002181, Fibrinogen_a/b/g_C_dom IPR020837, Fibrinogen_CS |
PANTHERi | PTHR19143:SF156, PTHR19143:SF156, 1 hit |
Pfami | View protein in Pfam PF00147, Fibrinogen_C, 1 hit |
SMARTi | View protein in SMART SM00186, FBG, 1 hit |
SUPFAMi | SSF56496, SSF56496, 1 hit |
PROSITEi | View protein in PROSITE PS00514, FIBRINOGEN_C_1, 1 hit PS51406, FIBRINOGEN_C_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q15389-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MTVFLSFAFL AAILTHIGCS NQRRSPENSG RRYNRIQHGQ CAYTFILPEH
60 70 80 90 100
DGNCRESTTD QYNTNALQRD APHVEPDFSS QKLQHLEHVM ENYTQWLQKL
110 120 130 140 150
ENYIVENMKS EMAQIQQNAV QNHTATMLEI GTSLLSQTAE QTRKLTDVET
160 170 180 190 200
QVLNQTSRLE IQLLENSLST YKLEKQLLQQ TNEILKIHEK NSLLEHKILE
210 220 230 240 250
MEGKHKEELD TLKEEKENLQ GLVTRQTYII QELEKQLNRA TTNNSVLQKQ
260 270 280 290 300
QLELMDTVHN LVNLCTKEGV LLKGGKREEE KPFRDCADVY QAGFNKSGIY
310 320 330 340 350
TIYINNMPEP KKVFCNMDVN GGGWTVIQHR EDGSLDFQRG WKEYKMGFGN
360 370 380 390 400
PSGEYWLGNE FIFAITSQRQ YMLRIELMDW EGNRAYSQYD RFHIGNEKQN
410 420 430 440 450
YRLYLKGHTG TAGKQSSLIL HGADFSTKDA DNDNCMCKCA LMLTGGWWFD
460 470 480 490
ACGPSNLNGM FYTAGQNHGK LNGIKWHYFK GPSYSLRSTT MMIRPLDF
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB4DTQ9 | B4DTQ9_HUMAN | Angiopoietin-1 | ANGPT1 | 298 | Annotation score: | ||
E7ERK4 | E7ERK4_HUMAN | Angiopoietin-1 | ANGPT1 | 297 | Annotation score: | ||
E5RFF4 | E5RFF4_HUMAN | Angiopoietin-1 | ANGPT1 | 30 | Annotation score: |
Sequence cautioni
The sequence BAA02793 differs from that shown. Reason: Erroneous initiation.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069165 | 247 | L → P. Corresponds to variant dbSNP:rs73701083Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_046324 | 269 | Missing in isoform 2. 3 Publications | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U83508 mRNA Translation: AAB50557.1 AB084454 mRNA Translation: BAB91325.1 AY121504 mRNA Translation: AAM81745.1 AY124380 mRNA Translation: AAM92271.1 D13628 mRNA Translation: BAA02793.2 Different initiation. BX648814 mRNA Translation: CAI45984.1 AC091010 Genomic DNA No translation available. AP000428 Genomic DNA No translation available. AP003480 Genomic DNA No translation available. CH471060 Genomic DNA Translation: EAW91909.1 BC152411 mRNA Translation: AAI52412.1 BC152419 mRNA Translation: AAI52420.1 |
CCDSi | CCDS56551.1 [Q15389-2] CCDS6306.1 [Q15389-1] |
RefSeqi | NP_001137.2, NM_001146.4 [Q15389-1] NP_001186788.1, NM_001199859.2 [Q15389-2] NP_001300980.1, NM_001314051.1 |
Genome annotation databases
Ensembli | ENST00000297450; ENSP00000297450; ENSG00000154188 [Q15389-2] ENST00000517746; ENSP00000428340; ENSG00000154188 [Q15389-1] |
GeneIDi | 284 |
KEGGi | hsa:284 |
UCSCi | uc003ymn.4, human [Q15389-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Angiopoietin entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U83508 mRNA Translation: AAB50557.1 AB084454 mRNA Translation: BAB91325.1 AY121504 mRNA Translation: AAM81745.1 AY124380 mRNA Translation: AAM92271.1 D13628 mRNA Translation: BAA02793.2 Different initiation. BX648814 mRNA Translation: CAI45984.1 AC091010 Genomic DNA No translation available. AP000428 Genomic DNA No translation available. AP003480 Genomic DNA No translation available. CH471060 Genomic DNA Translation: EAW91909.1 BC152411 mRNA Translation: AAI52412.1 BC152419 mRNA Translation: AAI52420.1 |
CCDSi | CCDS56551.1 [Q15389-2] CCDS6306.1 [Q15389-1] |
RefSeqi | NP_001137.2, NM_001146.4 [Q15389-1] NP_001186788.1, NM_001199859.2 [Q15389-2] NP_001300980.1, NM_001314051.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4EPU | X-ray | 2.10 | A/B | 282-497 | [»] | |
4JYO | X-ray | 2.50 | X | 280-498 | [»] | |
4K0V | X-ray | 4.51 | B | 280-498 | [»] | |
SMRi | Q15389 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 106781, 4 interactors |
IntActi | Q15389, 3 interactors |
MINTi | Q15389 |
STRINGi | 9606.ENSP00000428340 |
Chemistry databases
ChEMBLi | CHEMBL3217395 |
PTM databases
GlyGeni | Q15389, 5 sites |
iPTMneti | Q15389 |
PhosphoSitePlusi | Q15389 |
Genetic variation databases
BioMutai | ANGPT1 |
DMDMi | 12229574 |
Proteomic databases
jPOSTi | Q15389 |
MassIVEi | Q15389 |
PaxDbi | Q15389 |
PeptideAtlasi | Q15389 |
PRIDEi | Q15389 |
ProteomicsDBi | 60559 [Q15389-1] |
Protocols and materials databases
ABCDi | Q15389, 3 sequenced antibodies |
Antibodypediai | 4501, 656 antibodies |
DNASUi | 284 |
Genome annotation databases
Ensembli | ENST00000297450; ENSP00000297450; ENSG00000154188 [Q15389-2] ENST00000517746; ENSP00000428340; ENSG00000154188 [Q15389-1] |
GeneIDi | 284 |
KEGGi | hsa:284 |
UCSCi | uc003ymn.4, human [Q15389-1] |
Organism-specific databases
CTDi | 284 |
DisGeNETi | 284 |
GeneCardsi | ANGPT1 |
HGNCi | HGNC:484, ANGPT1 |
HPAi | ENSG00000154188, Low tissue specificity |
MalaCardsi | ANGPT1 |
MIMi | 601667, gene |
neXtProti | NX_Q15389 |
OpenTargetsi | ENSG00000154188 |
Orphaneti | 537891, ANGPT1-related hereditary angioedema with normal C1Inh |
PharmGKBi | PA24791 |
VEuPathDBi | HostDB:ENSG00000154188.9 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2579, Eukaryota |
GeneTreei | ENSGT00940000158117 |
HOGENOMi | CLU_038628_3_1_1 |
InParanoidi | Q15389 |
OMAi | EHRILEM |
OrthoDBi | 357340at2759 |
PhylomeDBi | Q15389 |
TreeFami | TF336658 |
Enzyme and pathway databases
PathwayCommonsi | Q15389 |
Reactomei | R-HSA-210993, Tie2 Signaling R-HSA-5673001, RAF/MAP kinase cascade |
SignaLinki | Q15389 |
SIGNORi | Q15389 |
Miscellaneous databases
BioGRID-ORCSi | 284, 7 hits in 874 CRISPR screens |
ChiTaRSi | ANGPT1, human |
GeneWikii | Angiopoietin_1 |
GenomeRNAii | 284 |
Pharosi | Q15389, Tbio |
PROi | PR:Q15389 |
RNActi | Q15389, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000154188, Expressed in cauda epididymis and 205 other tissues |
ExpressionAtlasi | Q15389, baseline and differential |
Genevisiblei | Q15389, HS |
Family and domain databases
CDDi | cd00087, FReD, 1 hit |
Gene3Di | 3.90.215.10, 1 hit 4.10.530.10, 1 hit |
InterProi | View protein in InterPro IPR028843, Ang-1 IPR036056, Fibrinogen-like_C IPR014716, Fibrinogen_a/b/g_C_1 IPR014715, Fibrinogen_a/b/g_C_2 IPR002181, Fibrinogen_a/b/g_C_dom IPR020837, Fibrinogen_CS |
PANTHERi | PTHR19143:SF156, PTHR19143:SF156, 1 hit |
Pfami | View protein in Pfam PF00147, Fibrinogen_C, 1 hit |
SMARTi | View protein in SMART SM00186, FBG, 1 hit |
SUPFAMi | SSF56496, SSF56496, 1 hit |
PROSITEi | View protein in PROSITE PS00514, FIBRINOGEN_C_1, 1 hit PS51406, FIBRINOGEN_C_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ANGP1_HUMAN | |
Accessioni | Q15389Primary (citable) accession number: Q15389 Secondary accession number(s): Q5HYA0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | January 1, 1998 | |
Last modified: | February 10, 2021 | |
This is version 184 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM