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ANXA4 annexin A4 [ Homo sapiens (human) ]

Gene ID: 307, updated on 11-Apr-2024

Summary

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Official Symbol
ANXA4provided by HGNC
Official Full Name
annexin A4provided by HGNC
Primary source
HGNC:HGNC:542
See related
Ensembl:ENSG00000196975 MIM:106491; AllianceGenome:HGNC:542
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ANX4; P32.5; PIG28; PP4-X; ZAP36; PAP-II; HEL-S-274
Summary
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]
Expression
Broad expression in gall bladder (RPKM 187.6), duodenum (RPKM 64.1) and 17 other tissues See more
Orthologs
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Genomic context

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See ANXA4 in Genome Data Viewer
Location:
2p13.3
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (69643808..69827112)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (69656119..69839380)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (69870940..70054244)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene AP2 associated kinase 1 Neighboring gene beta-1,3-N-acetylgalactosaminyltransferase 1 pseudogene 1 Neighboring gene ribosomal protein L36a pseudogene 16 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11597 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15975 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr2:69872055-69872657 Neighboring gene small nucleolar RNA U13 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15976 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11599 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11598 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15977 Neighboring gene SMARCA4 interacting SWI/SNF chromatin remodeling complex scaffold lncRNA Neighboring gene uncharacterized LOC124906021 Neighboring gene H3K27ac hESC enhancers GRCh37_chr2:70055828-70056749 and GRCh37_chr2:70056750-70057670 Neighboring gene germ cell-less 1, spermatogenesis associated Neighboring gene ribosomal protein L23a pseudogene 92 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:70120713-70121648 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:70121649-70122583 Neighboring gene small nuclear ribonucleoprotein U4/U6.U5 subunit 27

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Evidence of an Annexin A4 mediated plasma membrane repair response to biomechanical strain associated with glaucoma pathogenesis. Vicic N, et al. J Cell Physiol, 2022 Sep. PMID 35862065, Free PMC Article
  2. Membrane-cytoplasm translocation of annexin A4 is involved in the metastasis of colorectal carcinoma. Peng Y, et al. Aging (Albany NY), 2021 Mar 24. PMID 33761465, Free PMC Article
  3. Clinical Significance of Annexin A4 as a Biomarker in the Early Diagnosis of Hepatocellular Carcinoma. Saad ZM, et al. Asian Pac J Cancer Prev, 2020 Sep 1. PMID 32986366, Free PMC Article
  4. Lewis(y) antigen-mediated positive feedback loop induces and promotes chemotherapeutic resistance in ovarian cancer. Liu J, et al. Int J Oncol, 2018 Oct. PMID 30066907
  5. The Role of Annexin A4 in Triple-Negative Breast Cancer Progression and Its Clinical Application. Zhang ZG, et al. Ann Clin Lab Sci, 2016 Sep. PMID 27650619

See all (115) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Evidence of an Annexin A4 mediated plasma membrane repair response to biomechanical strain associated with glaucoma pathogenesis.
    Title: Evidence of an Annexin A4 mediated plasma membrane repair response to biomechanical strain associated with glaucoma pathogenesis.
  2. Membrane-cytoplasm translocation of annexin A4 is involved in the metastasis of colorectal carcinoma.
    Title: Membrane-cytoplasm translocation of annexin A4 is involved in the metastasis of colorectal carcinoma.
  3. p53 and ANXA4/NFkappaB p50 complexes regulate cell proliferation, apoptosis and tumor progression in ovarian clear cell carcinoma.
    Title: p53 and ANXA4/NF‑κB p50 complexes regulate cell proliferation, apoptosis and tumor progression in ovarian clear cell carcinoma.
  4. Clinical Significance of Annexin A4 as a Biomarker in the Early Diagnosis of Hepatocellular Carcinoma.
    Title: Clinical Significance of Annexin A4 as a Biomarker in the Early Diagnosis of Hepatocellular Carcinoma.
  5. GSK3beta-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration.
    Title: GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration.
  6. Bioinformatics analysis predicted that annexin A4 was a potential target gene of miR-203. Next, luciferase reporter assay confirmed that miR-203 could directly target annexin A4.
    Title: miR-203 Inhibits the Invasion and EMT of Gastric Cancer Cells by Directly Targeting Annexin A4.
  7. ANXA4 expression was increased at both the mRNA and protein level in the drugresistant ovarian cancer cells, and ANXA4 contained a Lewis(y) structure. ANXA4 overexpression can abnormally activate signaling pathways and regulate the expression of a numbers of factors, forming a positive feedback loop to induce the chemoresistance of ovarian cancer cells.
    Title: Lewis(y) antigen-mediated positive feedback loop induces and promotes chemotherapeutic resistance in ovarian cancer.
  8. Annexin A4 binds to artificial membranes and generates curvature force initiated from free edges, whereas annexin A6 induces constriction force.
    Title: Annexin A4 and A6 induce membrane curvature and constriction during cell membrane repair.
  9. Taken together, these data indicate that up-regulation of ANXA4 leads to activation of the NF-kappaB pathway and its target genes in a feedback regulatory mechanism via the p65 subunit, resulting in tumor growth in GBC.
    Title: Annexin A4-nuclear factor-κB feedback circuit regulates cell malignant behavior and tumor growth in gallbladder cancer.
  10. Upregulation and nuclear translocation of ANXA4 have been observed in the progression of colorectal cancer and ovarian serous carcinoma. Knockdown of ANXA4 attenuated migration in ovarian cancer and breast cancer cells. In contrast, knockdown of ANXA4 increased susceptibility to platinum in ovarian cancer and malignant mesothelioma cells. Review.
    Title: The role of annexin A4 in cancer.
Submit: New GeneRIF Correction See all GeneRIFs (39)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortiu
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 upregulates the expression of annexin A4 and V in umbilical cord blood mononuclear cells and T-cell lines but downregulates the expression of annexin A1 in umbilical cord blood mononuclear cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC75105, DKFZp686H02120

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables NF-kappaB binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables calcium ion binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables calcium-dependent phospholipid binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calcium-dependent phospholipid binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables calcium-dependent phospholipid binding NAS
Non-traceable Author Statement
more info
 PubMed 
enables calcium-dependent protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables phosphatidylserine binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables phospholipase inhibitor activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in Notch signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in epithelial cell differentiation IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in negative regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of apoptotic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of interleukin-8 production IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in cell surface IDA
Inferred from Direct Assay
more info
 PubMed 
located_in collagen-containing extracellular matrix HDA PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytoplasm TAS
Traceable Author Statement
more info
 PubMed 
located_in extracellular exosome HDA PubMed 
located_in nuclear membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in vesicle membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in vesicle membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in zymogen granule membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
annexin A4
Names
35-beta calcimedin
annexin IV (placental anticoagulant protein II)
annexin-4
carbohydrate-binding protein p33/p41
chromobindin-4
endonexin I
epididymis secretory protein Li 274
lipocortin IV
placental anticoagulant protein II
proliferation-inducing gene 28
proliferation-inducing protein 28
protein II

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001153.5 → NP_001144.1  annexin A4 isoform a

    See identical proteins and their annotated locations for NP_001144.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same isoform (a).
    Source sequence(s)
    AC019206, AK058017, BC000182, D78152, DB562261
    Consensus CDS
    CCDS1894.1
    UniProtKB/TrEMBL
    V9HW59
    Related
    ENSP00000377833.4, ENST00000394295.6
    Conserved Domains (1) summary
    pfam00191
    Location:251 → 316
    Annexin

  2. NM_001320698.2 → NP_001307627.1  annexin A4 isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1 and 2 both encode the same isoform (a).
    Source sequence(s)
    AC019206, AC092431, AK058017, BC000182, D78152, DB562261, DN994496
    Consensus CDS
    CCDS1894.1
    UniProtKB/TrEMBL
    V9HW59
    Conserved Domains (1) summary
    pfam00191
    Location:251 → 316
    Annexin

  3. NM_001320700.2 → NP_001307629.1  annexin A4 isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    AC019206, AK058017, BC063672, D78152, DB562261
    Consensus CDS
    CCDS82459.1
    UniProtKB/TrEMBL
    B4DDZ4, Q6P452
    Related
    ENSP00000386756.1, ENST00000409920.5
    Conserved Domains (2) summary
    smart00335
    Location:83 → 135
    ANX; Annexin repeats
    pfam00191
    Location:229 → 294
    Annexin; Annexin

  4. NM_001320702.2 → NP_001307631.1  annexin A4 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (c) is shorter at the N-terminus compared to isoform a.
    Source sequence(s)
    AC019206, AK058017, AK293177, D78152, DB562261
    UniProtKB/Swiss-Prot
    P09525
    UniProtKB/TrEMBL
    Q6P452
    Conserved Domains (1) summary
    pfam00191
    Location:167 → 232
    Annexin

  5. NM_001365496.2 → NP_001352425.1  annexin A4 isoform a

    Status: REVIEWED

    Source sequence(s)
    AA237007, AC019206, BX110594, CN287596, CU446263, DB562261, DC380425
    Consensus CDS
    CCDS1894.1
    UniProtKB/TrEMBL
    V9HW59
    Conserved Domains (1) summary
    pfam00191
    Location:251 → 316
    Annexin

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    69643808..69827112
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047444083.1 → XP_047300039.1  annexin A4 isoform X1

  2. XM_017003943.2 → XP_016859432.1  annexin A4 isoform X1

    UniProtKB/TrEMBL
    V9HW59
    Conserved Domains (1) summary
    pfam00191
    Location:251 → 316
    Annexin

  3. XM_024452835.2 → XP_024308603.1  annexin A4 isoform X1

    UniProtKB/TrEMBL
    V9HW59
    Conserved Domains (1) summary
    pfam00191
    Location:251 → 316
    Annexin

  4. XM_047444082.1 → XP_047300038.1  annexin A4 isoform X1

  5. XM_047444081.1 → XP_047300037.1  annexin A4 isoform X1

  6. XM_047444080.1 → XP_047300036.1  annexin A4 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    69656119..69839380
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341638.1 → XP_054197613.1  annexin A4 isoform X1

  2. XM_054341636.1 → XP_054197611.1  annexin A4 isoform X1

  3. XM_054341637.1 → XP_054197612.1  annexin A4 isoform X1

  4. XM_054341635.1 → XP_054197610.1  annexin A4 isoform X1

  5. XM_054341634.1 → XP_054197609.1  annexin A4 isoform X1

  6. XM_054341633.1 → XP_054197608.1  annexin A4 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P09525.4 GenPept UniProtKB/Swiss-Prot:P09525

Gene LinkOut

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