Seroatlas · Human Serome Atlas

ANGPTL4

Angiopoietin-related protein 4

Also known as: ANGL4_HUMAN, ARP4, FIAF, HFARP, NL2, PGAR, pp1158

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q9BY76
Gene: ANGPTL4
Ensembl: ENSG00000167772
Chromosome: 19
Canonical length: 406 aa
Protein class: Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins
Subcellular location: Nucleoplasm,Vesicles
Secretome location: Secreted to blood
Quaternary structure: Homooligomer

OverviewNCBI Gene

This gene encodes a glycosylated, secreted protein containing a C-terminal fibrinogen domain. The encoded protein is induced by peroxisome proliferation activators and functions as a serum hormone that regulates glucose homeostasis, lipid metabolism, and insulin sensitivity. This protein can also act as an apoptosis survival factor for vascular endothelial cells and can prevent metastasis by inhibiting vascular growth and tumor cell invasion. The C-terminal domain may be proteolytically-cleaved from the full-length secreted protein. Decreased expression of this gene has been associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. This gene was previously referred to as ANGPTL2 but has been renamed ANGPTL4. [provided by RefSeq, Sep 2013]

Canonical amino-acid sequenceUniProt

406 residues, UniProt reviewed canonical sequence.

>Q9BY76|ANGPTL4
     1  MSGAPTAGAA LMLCAATAVL LSAQGGPVQS KSPRFASWDE MNVLAHGLLQ LGQGLREHAE
    61  RTRSQLSALE RRLSACGSAC QGTEGSTDLP LAPESRVDPE VLHSLQTQLK AQNSRIQQLF
   121  HKVAQQQRHL EKQHLRIQHL QSQFGLLDHK HLDHEVAKPA RRKRLPEMAQ PVDPAHNVSR
   181  LHRLPRDCQE LFQVGERQSG LFEIQPQGSP PFLVNCKMTS DGGWTVIQRR HDGSVDFNRP
   241  WEAYKAGFGD PHGEFWLGLE KVHSITGDRN SRLAVQLRDW DGNAELLQFS VHLGGEDTAY
   301  SLQLTAPVAG QLGATTVPPS GLSVPFSTWD QDHDLRRDKN CAKSLSGGWW FGTCSHSNLN
   361  GQYFRSIPQQ RQKLKKGIFW KTWRGRYYPL QATTMLIQPM AAEAAS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ANGPTL4 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: 188 nTPM

Expression across tissuesHPA

Tissue

adipose tissue: 188 nTPM
liver: 177 nTPM
breast: 162 nTPM
pancreas: 69 nTPM
basal ganglia: 62 nTPM
blood vessel: 58 nTPM

Single-cell type

esophageal apical cells: 1000 nCPM
breast lactating cells: 723 nCPM
enterocytes: 586 nCPM
pancreatic acinar cells: 451 nCPM
hepatocytes: 221 nCPM
astrocytes: 219 nCPM

Immune cell

basophil: 3.3 nTPM
neutrophil: 0.8 nTPM
eosinophil: 0.4 nTPM
NK-cell: 0.3 nTPM
memory B-cell: 0.2 nTPM
T-reg: 0.2 nTPM

Brain region

midbrain: 55 nTPM
thalamus: 48 nTPM
white matter: 45 nTPM
basal ganglia: 43 nTPM
cerebral cortex: 40 nTPM
medulla oblongata: 40 nTPM

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): 1.28
gnomAD pLI: 0
gnomAD missense Z: 0.44
DepMap mean gene effect: -0.05
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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ANGPTL4 as an antibody target. Whether an autoantibody or antibody against ANGPTL4 could matter depends on whether native ANGPTL4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ANGPTL4 is annotated as secreted, so native ANGPTL4 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label ANGPTL4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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