ANXA4

Protein identityUniProt · HPA

UniProt accession

P09525

Gene

ANXA4

Ensembl

ENSG00000196975

Chromosome

2

Canonical length

319 aa

Protein class

Cancer-related genes, FDA approved drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

Annexin IV (ANX4) belongs to the annexin family of calcium-dependent phospholipid binding proteins. Although their functions are still not clearly defined, several members of the annexin family have been implicated in membrane-related events along exocytotic and endocytotic pathways. ANX4 has 45 to 59% identity with other members of its family and shares a similar size and exon-intron organization. Isolated from human placenta, ANX4 encodes a protein that has possible interactions with ATP, and has in vitro anticoagulant activity and also inhibits phospholipase A2 activity. ANX4 is almost exclusively expressed in epithelial cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2016]

Canonical amino-acid sequenceUniProt

319 residues, UniProt reviewed canonical sequence.

>P09525|ANXA4
     1  MATKGGTVKA ASGFNAMEDA QTLRKAMKGL GTDEDAIISV LAYRNTAQRQ EIRTAYKSTI
    61  GRDLIDDLKS ELSGNFEQVI VGMMTPTVLY DVQELRRAMK GAGTDEGCLI EILASRTPEE
   121  IRRISQTYQQ QYGRSLEDDI RSDTSFMFQR VLVSLSAGGR DEGNYLDDAL VRQDAQDLYE
   181  AGEKKWGTDE VKFLTVLCSR NRNHLLHVFD EYKRISQKDI EQSIKSETSG SFEDALLAIV
   241  KCMRNKSAYF AEKLYKSMKG LGTDDNTLIR VMVSRAEIDM LDIRAHFKRL YGKSLYSFIK
   301  GDTSGDYRKV LLVLCGGDD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ANXA4 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

535 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ANXA4.

Disease | ImmuneIEDB

Conditions an epitope on ANXA4 was assayed in.

• type 1 diabetes mellitus T cell

ReferencesPubMed · IEDB

Publications for ANXA4 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

1.02

gnomAD pLI

0

gnomAD missense Z

0.86

DepMap mean gene effect

0.06

DepMap dependency class

none

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

• epithelial cell differentiation
• negative regulation of apoptotic process
• negative regulation of canonical NF-kappaB signal transduction
• negative regulation of interleukin-8 production
• negative regulation of transcription by RNA polymerase II
• negative regulation of tumor necrosis factor-mediated signaling pathway
• Notch signaling pathway
• signal transduction

Molecular functions

• calcium ion binding
• calcium-dependent phospholipid binding
• calcium-dependent protein binding
• identical protein binding
• NF-kappaB binding
• phosphatidylserine binding
• phospholipase inhibitor activity
• transcription regulator inhibitor activity

Cellular components

• cell surface
• cytoplasm
• extracellular exosome
• extracellular matrix
• nuclear membrane
• nucleus
• perinuclear region of cytoplasm
• plasma membrane
• vesicle membrane
• zymogen granule membrane

Protein domainsUniProt · Pfam · InterPro

• Annexin
• Annexin repeat, conserved site
• Annexin repeat
• Annexin superfamily
• Annexin
• Annexin A4

KeywordsUniProt

• Acetylation
• Alternative initiation
• Annexin
• Calcium
• Calcium/phospholipid-binding
• Cytoplasmic vesicle
• Membrane
• Phosphoprotein
• Repeat