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Protein

Angiopoietin-1

Gene

Angpt1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (By similarity).By similarity

GO - Molecular functioni

  • receptor binding Source: MGI
  • receptor tyrosine kinase binding Source: MGI
  • vascular endothelial growth factor receptor binding Source: MGI

GO - Biological processi

  • activation of transmembrane receptor protein tyrosine kinase activity Source: MGI
  • angiogenesis Source: MGI
  • cardiac muscle tissue morphogenesis Source: DFLAT
  • cell-substrate adhesion Source: MGI
  • endocardium morphogenesis Source: DFLAT
  • endoderm development Source: MGI
  • glomerulus vasculature development Source: MGI
  • hemopoiesis Source: MGI
  • heparin biosynthetic process Source: MGI
  • in utero embryonic development Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • negative regulation of cell adhesion Source: MGI
  • negative regulation of cytokine secretion involved in immune response Source: MGI
  • negative regulation of endothelial cell apoptotic process Source: MGI
  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of protein import into nucleus Source: MGI
  • negative regulation of protein phosphorylation Source: MGI
  • negative regulation of vascular permeability Source: MGI
  • patterning of blood vessels Source: DFLAT
  • positive chemotaxis Source: MGI
  • positive regulation of blood vessel endothelial cell migration Source: MGI
  • positive regulation of cell adhesion Source: MGI
  • positive regulation of endothelial cell migration Source: DFLAT
  • positive regulation of ERK1 and ERK2 cascade Source: MGI
  • positive regulation of peptidyl-serine phosphorylation Source: MGI
  • positive regulation of peptidyl-tyrosine phosphorylation Source: MGI
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: MGI
  • positive regulation of protein kinase B signaling Source: MGI
  • positive regulation of protein ubiquitination Source: MGI
  • positive regulation of receptor internalization Source: MGI
  • positive regulation of vascular endothelial growth factor receptor signaling pathway Source: DFLAT
  • protein localization to cell surface Source: MGI
  • regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • regulation of macrophage migration inhibitory factor signaling pathway Source: MGI
  • regulation of protein binding Source: MGI
  • regulation of skeletal muscle satellite cell proliferation Source: MGI
  • regulation of tumor necrosis factor production Source: MGI
  • sprouting angiogenesis Source: MGI
  • Tie signaling pathway Source: DFLAT
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: MGI
  • vasculogenesis Source: DFLAT
  • vasculogenesis involved in coronary vascular morphogenesis Source: DFLAT
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Angiogenesis, Differentiation

Enzyme and pathway databases

ReactomeiR-MMU-210993. Tie2 Signaling.
R-MMU-5673001. RAF/MAP kinase cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-1
Short name:
ANG-1
Gene namesi
Name:Angpt1
Synonyms:Agpt
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:108448. Angpt1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Embryonically lethal. Embryos die at about 12.5 dpc, due to important developmental defects of the endocardium and myocardium, plus generalized defects in vascular development.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000000911120 – 498Angiopoietin-1Add BLAST479

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi92N-linked (GlcNAc...)Sequence analysis1
Glycosylationi122N-linked (GlcNAc...)Sequence analysis1
Glycosylationi154N-linked (GlcNAc...)Sequence analysis1
Glycosylationi243N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi286 ↔ 315PROSITE-ProRule annotation
Glycosylationi295N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi439 ↔ 452PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO08538.
PaxDbiO08538.
PRIDEiO08538.

PTM databases

iPTMnetiO08538.
PhosphoSitePlusiO08538.

Expressioni

Developmental stagei

Early in development, at E9 to E11, it is found most prominently in the heart myocardium surrounding the endocardium. Later, it becomes more widely distributed, most often in the mesenchyme surrounding developing vessels, in close association with endothelial cells.

Gene expression databases

BgeeiENSMUSG00000022309.
CleanExiMM_ANGPT1.
GenevisibleiO08538. MM.

Interactioni

Subunit structurei

Homooligomer. Interacts with TEK/TIE2 (By similarity).By similarity

GO - Molecular functioni

  • receptor binding Source: MGI
  • receptor tyrosine kinase binding Source: MGI
  • vascular endothelial growth factor receptor binding Source: MGI

Protein-protein interaction databases

DIPiDIP-6051N.
STRINGi10090.ENSMUSP00000022921.

Structurei

3D structure databases

ProteinModelPortaliO08538.
SMRiO08538.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini277 – 497Fibrinogen C-terminalPROSITE-ProRule annotationAdd BLAST221

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili81 – 119Sequence analysisAdd BLAST39
Coiled coili153 – 261Sequence analysisAdd BLAST109

Sequence similaritiesi

Contains 1 fibrinogen C-terminal domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiKOG2579. Eukaryota.
ENOG410ZYS4. LUCA.
GeneTreeiENSGT00760000118809.
HOVERGENiHBG001644.
InParanoidiO08538.
KOiK05465.
OMAiTSQRQYS.
OrthoDBiEOG091G03M1.
TreeFamiTF336658.

Family and domain databases

CDDicd00087. FReD. 1 hit.
Gene3Di3.90.215.10. 1 hit.
4.10.530.10. 1 hit.
InterProiIPR028843. Ang-1.
IPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR020837. Fibrinogen_CS.
[Graphical view]
PANTHERiPTHR19143:SF156. PTHR19143:SF156. 1 hit.
PfamiPF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTiSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMiSSF56496. SSF56496. 1 hit.
PROSITEiPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O08538-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTVFLSFAFF AAILTHIGCS NQRRNPENGG RRYNRIQHGQ CAYTFILPEH
60 70 80 90 100
DGNCRESATE 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 GLVSRQTFII QELEKQLSRA TNNNSILQKQ
260 270 280 290 300
QLELMDTVHN LISLCTKEGV LLKGGKREEE KPFRDCADVY QAGFNKSGIY
310 320 330 340 350
TIYFNNMPEP 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
Length:498
Mass (Da):57,519
Last modified:July 27, 2011 - v2
Checksum:iFC36F905A9E79074
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti262I → V in AAB50558 (PubMed:8980223).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83509 mRNA. Translation: AAB50558.1.
BC067410 mRNA. Translation: AAH67410.1.
CCDSiCCDS27450.1.
RefSeqiNP_033770.2. NM_009640.4.
UniGeneiMm.309336.

Genome annotation databases

EnsembliENSMUST00000022921; ENSMUSP00000022921; ENSMUSG00000022309.
GeneIDi11600.
KEGGimmu:11600.
UCSCiuc007vpc.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U83509 mRNA. Translation: AAB50558.1.
BC067410 mRNA. Translation: AAH67410.1.
CCDSiCCDS27450.1.
RefSeqiNP_033770.2. NM_009640.4.
UniGeneiMm.309336.

3D structure databases

ProteinModelPortaliO08538.
SMRiO08538.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-6051N.
STRINGi10090.ENSMUSP00000022921.

PTM databases

iPTMnetiO08538.
PhosphoSitePlusiO08538.

Proteomic databases

MaxQBiO08538.
PaxDbiO08538.
PRIDEiO08538.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022921; ENSMUSP00000022921; ENSMUSG00000022309.
GeneIDi11600.
KEGGimmu:11600.
UCSCiuc007vpc.2. mouse.

Organism-specific databases

CTDi284.
MGIiMGI:108448. Angpt1.

Phylogenomic databases

eggNOGiKOG2579. Eukaryota.
ENOG410ZYS4. LUCA.
GeneTreeiENSGT00760000118809.
HOVERGENiHBG001644.
InParanoidiO08538.
KOiK05465.
OMAiTSQRQYS.
OrthoDBiEOG091G03M1.
TreeFamiTF336658.

Enzyme and pathway databases

ReactomeiR-MMU-210993. Tie2 Signaling.
R-MMU-5673001. RAF/MAP kinase cascade.

Miscellaneous databases

ChiTaRSiAngpt1. mouse.
PROiO08538.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000022309.
CleanExiMM_ANGPT1.
GenevisibleiO08538. MM.

Family and domain databases

CDDicd00087. FReD. 1 hit.
Gene3Di3.90.215.10. 1 hit.
4.10.530.10. 1 hit.
InterProiIPR028843. Ang-1.
IPR014716. Fibrinogen_a/b/g_C_1.
IPR014715. Fibrinogen_a/b/g_C_2.
IPR002181. Fibrinogen_a/b/g_C_dom.
IPR020837. Fibrinogen_CS.
[Graphical view]
PANTHERiPTHR19143:SF156. PTHR19143:SF156. 1 hit.
PfamiPF00147. Fibrinogen_C. 1 hit.
[Graphical view]
SMARTiSM00186. FBG. 1 hit.
[Graphical view]
SUPFAMiSSF56496. SSF56496. 1 hit.
PROSITEiPS00514. FIBRINOGEN_C_1. 1 hit.
PS51406. FIBRINOGEN_C_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiANGP1_MOUSE
AccessioniPrimary (citable) accession number: O08538
Secondary accession number(s): Q6NWV7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.