ANGPT1

Protein identityUniProt · HPA

UniProt accession

Q15389

Gene

ANGPT1

Ensembl

ENSG00000154188

Chromosome

8

Canonical length

498 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins, RAS pathway related proteins

Secretome location

Secreted to blood

Quaternary structure

Homooligomer

OverviewNCBI Gene

This gene encodes a secreted glycoprotein that belongs to the angiopoietin family. Members of this family play important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The protein encoded by this gene is a secreted glycoprotein that activates the receptor by inducing its tyrosine phosphorylation. It plays a critical role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme and inhibits endothelial permeability. The protein also contributes to blood vessel maturation and stability, and may be involved in early development of the heart. Mutations in this gene are associated with hereditary angioedema. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

498 residues, UniProt reviewed canonical sequence.

>Q15389|ANGPT1
     1  MTVFLSFAFL AAILTHIGCS NQRRSPENSG RRYNRIQHGQ CAYTFILPEH DGNCRESTTD
    61  QYNTNALQRD APHVEPDFSS QKLQHLEHVM ENYTQWLQKL ENYIVENMKS EMAQIQQNAV
   121  QNHTATMLEI GTSLLSQTAE QTRKLTDVET QVLNQTSRLE IQLLENSLST YKLEKQLLQQ
   181  TNEILKIHEK NSLLEHKILE MEGKHKEELD TLKEEKENLQ GLVTRQTYII QELEKQLNRA
   241  TTNNSVLQKQ QLELMDTVHN LVNLCTKEGV LLKGGKREEE KPFRDCADVY QAGFNKSGIY
   301  TIYINNMPEP KKVFCNMDVN GGGWTVIQHR EDGSLDFQRG WKEYKMGFGN PSGEYWLGNE
   361  FIFAITSQRQ YMLRIELMDW EGNRAYSQYD RFHIGNEKQN YRLYLKGHTG TAGKQSSLIL
   421  HGADFSTKDA DNDNCMCKCA LMLTGGWWFD ACGPSNLNGM FYTAGQNHGK LNGIKWHYFK
   481  GPSYSLRSTT MMIRPLDF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ANGPT1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.41

Highest tissue expression

32 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ANGPT1.

Disease | AllUniProt

Conditions ANGPT1 is implicated in, by any mechanism.

• Angioedema, hereditary, 5 (HAE5) MIM:619361

ReferencesPubMed · IEDB

Publications for ANGPT1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.34

gnomAD pLI

0.95

gnomAD missense Z

1.3

DepMap mean gene effect

-0.06

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of transmembrane receptor protein tyrosine kinase activity
• angiogenesis
• blood coagulation
• cell-substrate adhesion
• glomerulus vasculature development
• hemopoiesis
• heparin proteoglycan biosynthetic process
• in utero embryonic development
• negative regulation of apoptotic process
• negative regulation of cell adhesion
• negative regulation of cytokine production involved in immune response
• negative regulation of endothelial cell apoptotic process
• negative regulation of neuron apoptotic process
• negative regulation of protein import into nucleus
• negative regulation of vascular endothelial growth factor signaling pathway
• negative regulation of vascular permeability
• neuron apoptotic process
• positive chemotaxis
• positive regulation of blood vessel endothelial cell migration
• positive regulation of blood-brain barrier permeability
• positive regulation of cell adhesion
• positive regulation of coagulation
• positive regulation of endothelial cell migration
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of gene expression
• positive regulation of peptidyl-tyrosine phosphorylation
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of protein ubiquitination
• positive regulation of receptor internalization
• protein localization to cell surface
• regulation of canonical NF-kappaB signal transduction
• regulation of skeletal muscle satellite cell proliferation
• regulation of tumor necrosis factor production
• sprouting angiogenesis
• Tie signaling pathway
• regulation of macrophage migration inhibitory factor signaling pathway

Molecular functions

• identical protein binding
• receptor ligand activity
• receptor tyrosine kinase binding

Cellular components

• extracellular exosome
• extracellular region
• extracellular space
• membrane raft
• microvillus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Fibrinogen, alpha/beta/gamma chain, C-terminal globular domain
• Fibrinogen, alpha/beta/gamma chain, C-terminal globular, subdomain 1
• Fibrinogen, conserved site
• Fibrinogen-like, C-terminal
• Fibrinogen/angiopoietin-like
• Angiopoietin-1/2/4 domain
• Fibrinogen beta and gamma chains, C-terminal globular domain
• ANG-1-like domain

KeywordsUniProt

• Angiogenesis
• Coiled coil
• Developmental protein
• Differentiation
• Disulfide bond
• Glycoprotein
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of ANGPT1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• THBD
• SVEP1
• TEK