ANXA5
Annexin A5
Also known as: ANX5, ANXA5_HUMAN, CPB-I, ENX2, PAP-I, RPRGL3, VAC-alph
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P08758
- Gene
- ANXA5
- Ensembl
- ENSG00000164111
- Chromosome
- 4
- Canonical length
- 320 aa
- Protein class
- Disease related genes, FDA approved drug targets, Plasma proteins, Predicted intracellular proteins, Transporters
- Subcellular location
- Nuclear membrane
OverviewNCBI Gene
The Annexin 5 gene spans 29 kb containing 13 exons, and encodes a single transcript of approximately 1.6 kb and a protein product with a molecular weight of about 35 kDa.The protein encoded by this gene belongs to the annexin family of calcium-dependent phospholipid binding proteins some of which have been implicated in membrane-related events along exocytotic and endocytotic pathways. Annexin 5 is a phospholipase A2 and protein kinase C inhibitory protein with calcium channel activity and a potential role in cellular signal transduction, inflammation, growth and differentiation. Annexin 5 has also been described as placental anticoagulant protein I, vascular anticoagulant-alpha, endonexin II, lipocortin V, placental protein 4 and anchorin CII. Polymorphisms in this gene have been implicated in various obstetric complications. [provided by RefSeq, Dec 2019]
Canonical amino-acid sequenceUniProt
320 residues, UniProt reviewed canonical sequence.
>P08758|ANXA5
1 MAQVLRGTVT DFPGFDERAD AETLRKAMKG LGTDEESILT LLTSRSNAQR QEISAAFKTL
61 FGRDLLDDLK SELTGKFEKL IVALMKPSRL YDAYELKHAL KGAGTNEKVL TEIIASRTPE
121 ELRAIKQVYE EEYGSSLEDD VVGDTSGYYQ RMLVVLLQAN RDPDAGIDEA QVEQDAQALF
181 QAGELKWGTD EEKFITIFGT RSVSHLRKVF DKYMTISGFQ IEETIDRETS GNLEQLLLAV
241 VKSIRSIPAY LAETLYYAMK GAGTDDHTLI RVMVSRSEID LFNIRKEFRK NFATSLYSMI
301 KGDTSGDYKK ALLLLCGEDDLocalizationUniProt · AlphaFold · HPA
Whether an antibody against ANXA5 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
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.25
- Highest tissue expression
- 460 nTPM
Expression across tissuesHPA
Tissue
- adipose tissue: 460 nTPM
- placenta: 438 nTPM
- cervix: 403 nTPM
- blood vessel: 400 nTPM
- smooth muscle: 346 nTPM
- breast: 323 nTPM
Single-cell type
- extravillous trophoblasts: 1,408 nCPM
- cytotrophoblasts: 1,348 nCPM
- syncytiotrophoblasts: 1,284 nCPM
- migrating cytotrophoblasts: 1,188 nCPM
- pancreatic duct cells: 1,031 nCPM
- monocytes: 891 nCPM
Immune cell
- intermediate monocyte: 831 nTPM
- non-classical monocyte: 801 nTPM
- total PBMC: 773 nTPM
- myeloid DC: 746 nTPM
- classical monocyte: 726 nTPM
- eosinophil: 361 nTPM
Brain region
- thalamus: 171 nTPM
- white matter: 169 nTPM
- medulla oblongata: 160 nTPM
- choroid plexus: 128 nTPM
- cerebellum: 125 nTPM
- hypothalamus: 123 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about ANXA5.
Disease | AllUniProt
Conditions ANXA5 is implicated in, by any mechanism.
- Pregnancy loss, recurrent, 3 (RPRGL3) MIM:614391
Disease | AutoantibodyPubMed
Conditions in which antibodies against ANXA5 are reported. Each links to that disease's full target list.
- Antiphospholipid Syndrome 39
- Abortion, Habitual 15
- Thrombosis 14
- Lupus Erythematosus, Systemic 13
- Abortion, Spontaneous 11
- Venous Thrombosis 5
- Stroke 4
- COVID-19 3
- Myocardial Infarction 3
- Pre-Eclampsia 3
Showing 10 of 12 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for ANXA5 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.
Reference: AutoantibodyPubMed
88 publications
- Noncriteria antiphospholipid antibodies in antiphospholipid syndrome.
2024 · Int J Lab Hematol · RCR 4.3 · 14 citations - Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody.
1994 · Am J Hematol · RCR 4.3 · 117 citations - Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nîmes Obstetricians and Haematologists Study--NOHA.
2000 · Thromb Haemost · RCR 4 · 125 citations - Non-criteria antiphospholipid antibodies in antiphospholipid syndrome: Diagnostic value added.
2022 · Front Immunol · RCR 3.2 · 27 citations - Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications.
2001 · Clin Chem · RCR 3.1 · 107 citations
Show 20 more of 88 total
- Annexin V is critical in the maintenance of murine placental integrity.
1999 · Am J Obstet Gynecol · RCR 2.9 · 104 citations - Anti-annexins autoantibodies: their role as biomarkers of autoimmune diseases.
2011 · Autoimmun Rev · RCR 2.8 · 90 citations - Non-conventional antiphospholipid antibodies in patients with clinical obstetrical APS: Prevalence and treatment efficacy in pregnancies.
2016 · Semin Arthritis Rheum · RCR 2.4 · 47 citations - Criteria and non-criteria antiphospholipid autoantibodies screening in patients with late pregnancy morbidity: A cross-sectional study.
2024 · Placenta · RCR 2.3 · 7 citations - Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression.
2011 · Am J Obstet Gynecol · RCR 2.3 · 64 citations - Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies.
2021 · Clin Rheumatol · RCR 2.2 · 32 citations - Anti-annexin V antibodies in patients with early pregnancy loss or implantation failures.
2001 · Fertil Steril · RCR 2.2 · 70 citations - Antiphospholipid/antiprotein antibodies, hemostasis-related autoantibodies, and plasma homocysteine as risk factors for a first early pregnancy loss: a matched case-control study.
2003 · Blood · RCR 2.2 · 72 citations - Lupus anticoagulant autoantibody induces apoptosis in umbilical vein endothelial cells: involvement of annexin V.
1994 · Biochem Biophys Res Commun · RCR 2.1 · 65 citations - The mosaic of "seronegative" antiphospholipid syndrome.
2014 · J Immunol Res · RCR 1.9 · 45 citations - Antiphospholipid antibodies disappearance in primary antiphospholipid syndrome: Thrombosis recurrence.
2017 · Autoimmun Rev · RCR 1.7 · 34 citations - Reduction of circulating annexin A5 levels and resistance to annexin A5 anticoagulant activity in women with recurrent spontaneous pregnancy losses.
2006 · Am J Obstet Gynecol · RCR 1.7 · 56 citations - Evaluation of the Diagnostic Value of Non-criteria Antibodies for Antiphospholipid Syndrome Patients in a Chinese Cohort.
2021 · Front Immunol · RCR 1.6 · 18 citations - Stroke and antiphospholipid syndrome-antiphospholipid antibodies are a risk factor for an ischemic cerebrovascular event.
2019 · Clin Rheumatol · RCR 1.6 · 25 citations - Localization of the apoptosis-inducing activity of lupus anticoagulant in an annexin V-binding antibody subset.
1998 · J Clin Invest · RCR 1.6 · 62 citations - Anti-beta 2 glycoprotein 1 and anti-annexin V antibodies in women with recurrent miscarriage.
2001 · Br J Haematol · RCR 1.5 · 51 citations - Non beta 2-glycoprotein I cofactors for antiphospholipid antibodies.
1996 · Lupus · RCR 1.5 · 40 citations - Annexin A5 polymorphism (-1C-->T) and the presence of anti-annexin A5 antibodies in the antiphospholipid syndrome.
2006 · Ann Rheum Dis · RCR 1.4 · 49 citations - Clinical laboratory testing for the antiphospholipid syndrome.
2005 · Clin Chim Acta · RCR 1.4 · 42 citations - Circulating B lymphocytes producing autoantibodies to endothelial cells play a role in the pathogenesis of Takayasu arteritis.
2011 · J Vasc Surg · RCR 1.3 · 42 citations
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)
- 1.45
- gnomAD pLI
- 0
- gnomAD missense Z
- 0.55
- DepMap mean gene effect
- 0.08
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- blood coagulation
- negative regulation of apoptotic process
- negative regulation of coagulation
- signal transduction
Molecular functions
- calcium ion binding
- calcium-dependent phospholipid binding
- phosphatidylserine binding
- phospholipase inhibitor activity
- phospholipid binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of ANXA5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads ANXA5 as an antibody target. Whether an autoantibody or antibody against ANXA5 could matter depends on whether native ANXA5 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
ANXA5 is annotated at the cell surface, where native ANXA5 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label ANXA5 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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