ANXA4 annexin A4 [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

Location:: 2p13.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (69643808..69827112)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (69656119..69839380)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (69870940..70054244)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
GSK3beta-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration.
Title: GSK3β-Ikaros-ANXA4 signaling inhibits high-glucose-induced fibroblast migration.
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.
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.
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.
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.
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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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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

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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

RH65876 (e-PCR)
- UniSTS:70428

RH1484 (e-PCR)
- UniSTS:27743

ANXA4_2332 (e-PCR)
- UniSTS:280442

RH36905 (e-PCR)
- UniSTS:87932

D2S2560 (e-PCR)
- UniSTS:60046

SHGC-83751 (e-PCR)
- UniSTS:104345

D2S2862 (e-PCR)
- UniSTS:43168

L18441 (e-PCR)
- UniSTS:71348

SHGC-15259 (e-PCR)
- UniSTS:8665

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 more info	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 more info	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)

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
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
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
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
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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

69643808..69827112

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047444083.1 → XP_047300039.1 annexin A4 isoform X1
XM_017003943.2 → XP_016859432.1 annexin A4 isoform X1

UniProtKB/TrEMBL

V9HW59

Conserved Domains (1) summary

pfam00191
Location:251 → 316

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

UniProtKB/TrEMBL

V9HW59

Conserved Domains (1) summary

pfam00191
Location:251 → 316

Annexin
XM_047444082.1 → XP_047300038.1 annexin A4 isoform X1
XM_047444081.1 → XP_047300037.1 annexin A4 isoform X1
XM_047444080.1 → XP_047300036.1 annexin A4 isoform X1