ANGPTL3

Protein identityUniProt · HPA

UniProt accession

Q9Y5C1

Gene

ANGPTL3

Ensembl

ENSG00000132855

Chromosome

1

Canonical length

460 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a member of a family of secreted proteins that function in angiogenesis. The encoded protein, which is expressed predominantly in the liver, is further processed into an N-terminal coiled-coil domain-containing chain and a C-terminal fibrinogen chain. The N-terminal chain is important for lipid metabolism, while the C-terminal chain may be involved in angiogenesis. Mutations in this gene cause familial hypobetalipoproteinemia type 2. [provided by RefSeq, Aug 2015]

Canonical amino-acid sequenceUniProt

460 residues, UniProt reviewed canonical sequence.

>Q9Y5C1|ANGPTL3
     1  MFTIKLLLFI VPLVISSRID QDNSSFDSLS PEPKSRFAML DDVKILANGL LQLGHGLKDF
    61  VHKTKGQIND IFQKLNIFDQ SFYDLSLQTS EIKEEEKELR RTTYKLQVKN EEVKNMSLEL
   121  NSKLESLLEE KILLQQKVKY LEEQLTNLIQ NQPETPEHPE VTSLKTFVEK QDNSIKDLLQ
   181  TVEDQYKQLN QQHSQIKEIE NQLRRTSIQE PTEISLSSKP RAPRTTPFLQ LNEIRNVKHD
   241  GIPAECTTIY NRGEHTSGMY AIRPSNSQVF HVYCDVISGS PWTLIQHRID GSQNFNETWE
   301  NYKYGFGRLD GEFWLGLEKI YSIVKQSNYV LRIELEDWKD NKHYIEYSFY LGNHETNYTL
   361  HLVAITGNVP NAIPENKDLV FSTWDHKAKG HFNCPEGYSG GWWWHDECGE NNLNGKYNKP
   421  RAKSKPERRR GLSWKSQNGR LYSIKSTKML IHPTDSESFE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ANGPTL3 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)

0.42

Highest tissue expression

632 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ANGPTL3.

Disease | AllUniProt

Conditions ANGPTL3 is implicated in, by any mechanism.

• Hypobetalipoproteinemia, familial, 2 (FHBL2) MIM:605019

Disease | GeneticClinVar

15 pathogenic / likely-pathogenic of 140 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial hypobetalipoproteinemia 2
• Inborn genetic diseases
• Developmental and epileptic encephalopathy, 23

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)

1.3

gnomAD pLI

0

gnomAD missense Z

-0.09

DepMap mean gene effect

0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acylglycerol homeostasis
• angiogenesis
• artery morphogenesis
• cell-matrix adhesion
• cholesterol homeostasis
• cholesterol metabolic process
• fatty acid metabolic process
• glycerol metabolic process
• integrin-mediated signaling pathway
• lipid homeostasis
• lipid storage
• negative regulation of very-low-density lipoprotein particle remodeling
• phospholipid catabolic process
• phospholipid homeostasis
• phospholipid metabolic process
• positive regulation of angiogenesis
• positive regulation of cell migration
• positive regulation of lipid catabolic process
• regulation of chylomicron remodeling
• response to hormone
• signal transduction
• triglyceride homeostasis

Molecular functions

• enzyme inhibitor activity
• growth factor activity
• heparin binding
• integrin binding
• lipase binding
• lipase inhibitor activity
• phospholipase inhibitor activity

Cellular components

• cell surface
• early endosome
• extracellular region
• extracellular space
• Golgi apparatus
• lamellipodium

Protein domainsUniProt · Pfam · InterPro

• Fibrinogen, alpha/beta/gamma chain, C-terminal globular domain
• Fibrinogen, alpha/beta/gamma chain, C-terminal globular, subdomain 1
• Fibrinogen-like, C-terminal
• Fibrinogen C-terminal domain-containing protein
• Fibrinogen beta and gamma chains, C-terminal globular domain

KeywordsUniProt

• Angiogenesis
• Cell adhesion
• Cell projection
• Coiled coil
• Disulfide bond
• Glycoprotein
• Heparin-binding
• Lipid metabolism
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of ANGPTL3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ANGPTL8
• ITGB3