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Protein

Angiopoietin-1

Gene

ANGPT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.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

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processAngiogenesis, Differentiation

Enzyme and pathway databases

ReactomeiR-HSA-210993 Tie2 Signaling
R-HSA-5673001 RAF/MAP kinase cascade
SignaLinkiQ15389
SIGNORiQ15389

Names & Taxonomyi

Protein namesi
Recommended name:
Angiopoietin-1
Short name:
ANG-1
Gene namesi
Name:ANGPT1
Synonyms:KIAA0003
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000154188.9
HGNCiHGNC:484 ANGPT1
MIMi601667 gene
neXtProtiNX_Q15389

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi284
OpenTargetsiENSG00000154188
PharmGKBiPA24791

Chemistry databases

ChEMBLiCHEMBL3217395

Polymorphism and mutation databases

BioMutaiANGPT1
DMDMi12229574

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 15Sequence analysisAdd BLAST15
ChainiPRO_000000911016 – 498Angiopoietin-1Add BLAST483

Amino acid modifications

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

Post-translational modificationi

Glycosylated.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ15389
PeptideAtlasiQ15389
PRIDEiQ15389
ProteomicsDBi60559

PTM databases

iPTMnetiQ15389
PhosphoSitePlusiQ15389

Expressioni

Gene expression databases

BgeeiENSG00000154188
CleanExiHS_ANGPT1
ExpressionAtlasiQ15389 baseline and differential
GenevisibleiQ15389 HS

Organism-specific databases

HPAiCAB017815
HPA018793
HPA018816

Interactioni

Subunit structurei

Homooligomer. Interacts with TEK/TIE2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAPK8IP2Q133873EBI-10692491,EBI-722813

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106781, 2 interactors
IntActiQ15389, 2 interactors
STRINGi9606.ENSP00000428340

Structurei

Secondary structure

1498
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi286 – 291Combined sources6
Beta strandi298 – 302Combined sources5
Beta strandi311 – 316Combined sources6
Helixi319 – 321Combined sources3
Beta strandi324 – 333Combined sources10
Helixi341 – 346Combined sources6
Beta strandi353 – 356Combined sources4
Helixi359 – 366Combined sources8
Beta strandi371 – 378Combined sources8
Beta strandi384 – 394Combined sources11
Helixi397 – 399Combined sources3
Beta strandi403 – 412Combined sources10
Beta strandi433 – 437Combined sources5
Helixi439 – 443Combined sources5
Beta strandi450 – 452Combined sources3
Beta strandi454 – 456Combined sources3
Turni463 – 467Combined sources5
Beta strandi473 – 476Combined sources4
Turni477 – 479Combined sources3
Beta strandi487 – 495Combined sources9

3D structure databases

ProteinModelPortaliQ15389
SMRiQ15389
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

Keywords - Domaini

Coiled coil, Signal

Phylogenomic databases

eggNOGiKOG2579 Eukaryota
ENOG410ZYS4 LUCA
GeneTreeiENSGT00920000148944
HOGENOMiHOG000037128
HOVERGENiHBG001644
InParanoidiQ15389
KOiK05465
OMAiVFCNMDL
OrthoDBiEOG091G03M1
PhylomeDBiQ15389
TreeFamiTF336658

Family and domain databases

CDDicd00087 FReD, 1 hit
Gene3Di3.90.215.10, 1 hit
4.10.530.10, 1 hit
InterProiView 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
PANTHERiPTHR19143:SF156 PTHR19143:SF156, 1 hit
PfamiView protein in Pfam
PF00147 Fibrinogen_C, 1 hit
SMARTiView protein in SMART
SM00186 FBG, 1 hit
SUPFAMiSSF56496 SSF56496, 1 hit
PROSITEiView protein in PROSITE
PS00514 FIBRINOGEN_C_1, 1 hit
PS51406 FIBRINOGEN_C_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15389-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:498
Mass (Da):57,513
Last modified:January 1, 1998 - v2
Checksum:i5D5FA63AEF6BE920
GO
Isoform 2 (identifier: Q15389-2) [UniParc]FASTAAdd to basket
Also known as: Gly-269 del

The sequence of this isoform differs from the canonical sequence as follows:
     269-269: Missing.

Show »
Length:497
Mass (Da):57,456
Checksum:i3055148F097AC6AF
GO

Sequence cautioni

The sequence BAA02793 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069165247L → P. Corresponds to variant dbSNP:rs73701083Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046324269Missing in isoform 2. 3 Publications1

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
CCDSiCCDS56551.1 [Q15389-2]
CCDS6306.1 [Q15389-1]
RefSeqiNP_001137.2, NM_001146.4 [Q15389-1]
NP_001186788.1, NM_001199859.2 [Q15389-2]
NP_001300980.1, NM_001314051.1
UniGeneiHs.369675

Genome annotation databases

EnsembliENST00000297450; ENSP00000297450; ENSG00000154188 [Q15389-2]
ENST00000517746; ENSP00000428340; ENSG00000154188 [Q15389-1]
GeneIDi284
KEGGihsa:284
UCSCiuc003ymn.4 human [Q15389-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiANGP1_HUMAN
AccessioniPrimary (citable) accession number: Q15389
Secondary accession number(s): Q5HYA0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 1, 1998
Last modified: June 20, 2018
This is version 165 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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