ANXA1

Summary

ANXA1 (annexin A1, HGNC:533) is a protein-coding gene on chromosome 9q21.13, encoding Annexin A1 (P04083). Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process.

This gene encodes a membrane-localized protein that binds phospholipids. This protein inhibits phospholipase A2 and has anti-inflammatory activity. Loss of function or expression of this gene has been detected in multiple tumors.

Source: NCBI Gene 301 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 93 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000700

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:533
Approved symbol	ANXA1
Name	annexin A1
Location	9q21.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135046
Ensembl biotype	protein_coding
OMIM	151690
Entrez	301

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 25 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000257497, ENST00000376911, ENST00000415424, ENST00000456643, ENST00000468639, ENST00000489109, ENST00000491192, ENST00000495713, ENST00000857789, ENST00000857790, ENST00000857791, ENST00000857792, ENST00000857793, ENST00000857794, ENST00000857795, ENST00000857796, ENST00000857797, ENST00000954795, ENST00000954796, ENST00000954797, ENST00000954798, ENST00000954799, ENST00000954800, ENST00000954801, ENST00000954802, ENST00000954803, ENST00000954804, ENST00000954805, ENST00000954806

RefSeq mRNA: 1 — MANE Select: NM_000700 NM_000700

CCDS: CCDS6645

Canonical transcript exons

ENST00000257497 — 13 exons

Exon	Start	End
ENSE00000706585	73159329	73159423
ENSE00001198999	73151865	73151924
ENSE00001628663	73167497	73167555
ENSE00001650954	73169032	73169154
ENSE00003463283	73163476	73163532
ENSE00003508731	73162782	73162861
ENSE00003513338	73170051	73170393
ENSE00003543664	73165116	73165209
ENSE00003569681	73158522	73158601
ENSE00003612693	73160263	73160376
ENSE00003651204	73158695	73158803
ENSE00003677609	73166097	73166192
ENSE00003691979	73160803	73160893

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 326.9519 / max 19411.9811, expressed in 1760 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96934	317.3791	1759
96931	3.0969	1140
96933	2.8445	1113
96932	1.0854	644
96941	0.9150	487
96939	0.8670	522
96938	0.4892	245
205512	0.1841	70
96936	0.0514	4
96937	0.0391	10

Top tissues by expression

298 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oral cavity	UBERON:0000167	99.96	gold quality
pharyngeal mucosa	UBERON:0000355	99.96	gold quality
lower esophagus mucosa	UBERON:0035834	99.96	gold quality
tongue squamous epithelium	UBERON:0006919	99.94	gold quality
gingiva	UBERON:0001828	99.91	gold quality
gingival epithelium	UBERON:0001949	99.90	gold quality
esophagus mucosa	UBERON:0002469	99.90	gold quality
body of tongue	UBERON:0011876	99.88	gold quality
squamous epithelium	UBERON:0006914	99.87	gold quality
amniotic fluid	UBERON:0000173	99.86	gold quality
esophagus squamous epithelium	UBERON:0006920	99.85	gold quality
cervix squamous epithelium	UBERON:0006922	99.85	gold quality
calcaneal tendon	UBERON:0003701	99.84	gold quality
palpebral conjunctiva	UBERON:0001812	99.83	gold quality
epithelium of nasopharynx	UBERON:0001951	99.82	gold quality
cervix epithelium	UBERON:0004801	99.82	gold quality
nasal cavity epithelium	UBERON:0005384	99.82	gold quality
nasopharynx	UBERON:0001728	99.81	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.78	gold quality
bronchial epithelial cell	CL:0002328	99.76	gold quality
epithelium of esophagus	UBERON:0001976	99.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.72	gold quality
nasal cavity mucosa	UBERON:0001826	99.68	gold quality
tongue	UBERON:0001723	99.66	gold quality
epithelium of bronchus	UBERON:0002031	99.66	gold quality
bronchus	UBERON:0002185	99.64	gold quality
monocyte	CL:0000576	99.63	gold quality
mouth mucosa	UBERON:0003729	99.63	gold quality
mononuclear cell	CL:0000842	99.62	gold quality
placenta	UBERON:0001987	99.61	gold quality

Single-cell (SCXA)

Detected in 52 experiment(s), a significant marker in 43.

Experiment	Marker?	Max mean expression
E-CURD-89	yes	26704.89
E-HCAD-1	yes	14772.27
E-GEOD-135922	yes	12540.90
E-MTAB-10596	yes	9043.34
E-GEOD-89232	yes	8213.87
E-HCAD-24	yes	7921.30
E-CURD-97	yes	7477.19
E-MTAB-10855	yes	6268.64
E-MTAB-8221	yes	5953.46
E-MTAB-6701	yes	5340.32
E-HCAD-23	yes	5333.32
E-CURD-88	yes	4463.07
E-CURD-114	yes	4336.05
E-HCAD-13	yes	4057.50
E-MTAB-7407	yes	4054.50

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
IL1B	Activation
IL6	Activation
TNF	Activation

Upstream regulators (CollecTRI, top): CEBPA, NR3C1, RUNX1, SPI1, STAT3, TP53

miRNA regulators (miRDB)

41 targeting ANXA1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-3675-3P	99.09	67.70	968

Literature-anchored findings (GeneRIF, showing 40)

• ANXA1-derived peptides inhibit antigen-driven cellular proliferation and cytokine production in vitro. (PMID:11468004)
• 17beta-estradiol promotes the synthesis and the secretion of annexin I in the CCRF-CEM human cell line. (PMID:11759108)
• interferes with a leukocyte endothelial step essential for U937 cell, and possibly monocyte, transmigration both in vitro and in vivo (PMID:12165536)
• ANXA1 secretion in lymphocytes is unlikely to involve the classical ER-Golgi pathway; requires a Ca(2+)-dependent cleavage of ANXA1; involves both Ca(2+)-dependent and independent mechanisms; and is apparently independent of the GC receptor alpha isoform (PMID:12236584)
• This protein is translocated from cellular membrane to the nuclear membrane in human esophageal squamous cell carcinoma. (PMID:12679902)
• These results showed that annexin I binds to a surface receptor in order to regulate the stimulation of insulin release in MIN6N8a cells. (PMID:12859969)
• The gene expression profile of ALD is dominated by alcohol metabolism and inflammation and differs from other liver diseases. Annexins may play a role in the progression of fibrosis in ALD. (PMID:14633604)
• Annexin-I has a role in drug resistance in tumor cells (PMID:14733945)
• annexin II serves as both ligand and receptor in promoting phagocytosis. (PMID:15064349)
• ANXA1 has roles in neutrophil apoptosis [review] (PMID:15157173)
• Annexin I was expressed in vivo in lungs containing metastasized MDA-MB-435 cells but not in normal lung tissue of athymic mice, suggesting that it is an important cellular protein that is down regulated through BRMS1 mediated metastasis suppression. (PMID:15168732)
• an annexin 1 peptide can activate FPR, FPRL1, and FPRL2; results indicate that annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family. (PMID:15187149)
• annexin I is not the tumor suppressor gene corresponding to the high levels of loss of heterozygosity observed on chromosome 9 in esophageal squamous cell carcinoma (PMID:15447985)
• Data show that there is no association of these SNPs in ANXA1 gene with type 2 diabetes in Shanghai Han population. (PMID:15476183)
• Human colon adenocarcinoma cell differentiation is associated with an up-regulation of AnxA1, AnxA2, and AnxA5 and with a subcellular relocation of these proteins (PMID:15526283)
• annexin1 exerted its erythropoiesis regulating effect by ERK pathway (PMID:15883023)
• Results show that progression from prostatic intraepithelial neoplasia to prostate cancer is characterized by a reduction of ANX1 and suggest that downregulation of this protein could represent an important event in prostate carcinogenesis. (PMID:15944914)
• These results suggest that annexin A1 may be a key protein involved in CF pathogenesis especially in relation to the not well defined field of inflammation in CF. (PMID:16014420)
• annexin A1 and A2 may have roles in dysferlin deficiency and in muscular dystrophies (PMID:16100712)
• ANXA1 expression is decreased in prostatic adenocarcinoma and in high-grade prostatic intraepithelial neoplasia. (PMID:16324197)
• gene expression of CCR10 was increased by recombinant ANXA1 and the N-terminal ANXA1 peptide (PMID:16460738)
• ANXA1 and Gal-3 changed in their content and localization when neutrophils adhere to endothelia. In contrast, a decrease in the total amounts of Gal-1 was detected in migrated compared to non-migrated neutrophils. (PMID:16530434)
• ANXA1 expression may correlate with the tumorigenesis suggesting that the protein may represent an effective differentiation marker in thyroid cancer. (PMID:16627980)
• AnxA1 has a role in stimulating SKCO-15 cell migration through nFPR activation (PMID:16675446)
• Annexin I may have tumor suppressor functions in prostate cancer. The pro-apoptotic effect of ANX I involves the activation of p38 and JNK, which appears to shift the balance of signal transduction away from proliferation and toward apoptosis. (PMID:16741918)
• glucocorticoids and IL-1beta upregulate the synthesis and translocation of annexin I in rheumatoid synovial cells, but interdependent signalling pathways are involved (PMID:16883066)
• The high ANXA1 expression is frequent in esophageal and esophagogastric junction adenocarcinomas, correlates with more advanced pathologic T stage and the presence of distant metastasis, and is an independent prognostic factor for patient survival. (PMID:16899607)
• results suggest that suppressed ANXA1 expression in breast tissue is correlated with breast cancer development and progression (PMID:16949910)
• In view of the wide range of endogenous ligands known to interact with FPRL-1, including the anti-inflammatory protein annexin-A1, we speculate that the novel effect here described may impact on the immunosuppressive properties of glucocorticoids. (PMID:16973129)
• Ca2+ entering through a disruption locally induces annexin A1 binding to membranes, initiating emergency fusion events whenever and wherever required. (PMID:16984915)
• CD4+ cells from patients with rheumatoid arthritis showed a marked up-regulation of annexin-1 expression; annexin-1 is a molecular “tuner” of TCR signaling (PMID:17008549)
• Decrease of annexin-I expression is associated with bladder cancer development (PMID:17019707)
• The identification of annexin 1 as a substrate for HLE supports the model in which annexin 1 participates in regulating leukocyte emigration into inflamed tissue. (PMID:17023068)
• Annexin 1 has roles in a variety of inflammatory pathways, on cell proliferation machinery, in the regulation of cell death signaling, in phagocytic clearance of apoptosing cells, and most importantly in the process of carcinogenesis [review] (PMID:17215481)
• the role of the homeostatic antiinflammatory axis centered on annexin 1 in cerebral microvascular dysfunction and tissue injury associated with middle cerebral artery occlusion and reperfusion (PMID:17317721)
• Results demonstrated that ANXA1 plays a regulatory role in laryngeal cancer cell growth. (PMID:17340616)
• Annexin-1 and peptide derivatives play a role in promoting the resolution of inflammation. (PMID:17372018)
• LMP1 mediates serine phosphorylation of Annexin I via the PKC pathway. (PMID:17626739)
• proteinase 3 has a critical role in annexin 1 cleavage in activated neutrophils (PMID:17681950)
• the confluence-dependent interaction of cPLA(2)alpha and annexin A1 at the Golgi acts as a novel molecular switch controlling cPLA(2)alpha activity and endothelial cell prostaglandin generation. (PMID:17873281)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	anxa1a	ENSDARG00000026726
danio_rerio	anxa1d	ENSDARG00000098481
danio_rerio	anxa1b	ENSDARG00000100095
danio_rerio	anxa1c	ENSDARG00000104359
mus_musculus	Anxa1	ENSMUSG00000024659
rattus_norvegicus	Anxa1	ENSRNOG00000017469
drosophila_melanogaster	AnxB9	FBGN0000083
drosophila_melanogaster	AnxB11	FBGN0030749

Paralogs (12): ANXA13 (ENSG00000104537), ANXA10 (ENSG00000109511), ANXA11 (ENSG00000122359), ANXA7 (ENSG00000138279), ANXA3 (ENSG00000138772), ANXA9 (ENSG00000143412), ANXA5 (ENSG00000164111), ANXA2 (ENSG00000182718), ANXA4 (ENSG00000196975), ANXA6 (ENSG00000197043), ANXA8L1 (ENSG00000264230), ANXA8 (ENSG00000265190)

Protein

Protein identifiers

Annexin A1 — P04083 (reviewed: P04083)

Alternative names: Annexin I, Annexin-1, Calpactin II, Calpactin-2, Chromobindin-9, Lipocortin I, Phospholipase A2 inhibitory protein, p35

All UniProt accessions (4): P04083, Q5T3N0, Q5T3N1, Q5TZZ9

UniProt curated annotations — full annotation on UniProt →

Function. Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity. Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response. Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T cells. Promotes the differentiation of T cells into Th1 cells and negatively regulates differentiation into Th2 cells. Has no effect on unstimulated T cells. Negatively regulates hormone exocytosis via activation of the formyl peptide receptors and reorganization of the actin cytoskeleton. Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions. Displays Ca(2+)-dependent binding to phospholipid membranes. Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton. In the context of antitumor immunity, interacts with FPR1 on dendritic cells allowing for tumor-associated antigens uptake and cross-presentation to T cells to mount an antitumor specific T cell response. Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades. Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors. Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration. Promotes resolution of inflammation and wound healing. Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2.

Subunit / interactions. Homodimer; non-covalently linked. Homodimer; linked by transglutamylation. Homodimers linked by transglutamylation are observed in placenta, but not in other tissues. Interacts with S100A11. Heterotetramer, formed by two molecules each of S100A11 and ANXA1. Interacts with DYSF. Interacts with EGFR.

Subcellular location. Nucleus. Cytoplasm. Cell projection. Cilium. Cell membrane. Membrane. Endosome membrane. Basolateral cell membrane. Apical cell membrane. Lateral cell membrane. Secreted. Extracellular space. Extracellular exosome. Cytoplasmic vesicle. Secretory vesicle lumen. Phagocytic cup. Early endosome. Cytoplasmic vesicle membrane.

Tissue specificity. Detected in resting neutrophils. Detected in peripheral blood T cells. Detected in extracellular vesicles in blood serum from patients with inflammatory bowel disease, but not in serum from healthy donors. Detected in placenta (at protein level). Detected in liver.

Post-translational modifications. Phosphorylated by protein kinase C, EGFR and TRPM7. Phosphorylated in response to EGF treatment. Sumoylated. Proteolytically cleaved by cathepsin CTSG to release the active N-terminal peptide Ac2-26.

Domain organisation. The full-length protein can bind eight Ca(2+) ions via the annexin repeats. Calcium binding causes a major conformation change that modifies dimer contacts and leads to surface exposure of the N-terminal phosphorylation sites; in the absence of Ca(2+), these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding.

Miscellaneous. Was originally identified as calcium and phospholipid binding protein that displays Ca(2+)-dependent binding to phospholipid membranes and can promote membrane aggregation in vitro. Was initially identified as inhibitor of phospholipase A2 activity (in vitro). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates.

Similarity. Belongs to the annexin family.

RefSeq proteins (1): NP_000691* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001464	Annexin	Family
IPR002388	ANX1	Family
IPR018252	Annexin_repeat_CS	Conserved_site
IPR018502	Annexin_repeat	Repeat
IPR037104	Annexin_sf	Homologous_superfamily

Pfam: PF00191

UniProt features (64 total): binding site 26, modified residue 11, helix 8, cross-link 5, repeat 4, mutagenesis site 3, initiator methionine 1, chain 1, peptide 1, site 1, disulfide bond 1, sequence conflict 1, strand 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
1QLS	X-RAY DIFFRACTION	2.3
1AIN	X-RAY DIFFRACTION	2.5
9NP0	ELECTRON MICROSCOPY	3.32
1BO9	SOLUTION NMR
5VFW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04083-F1	95.56	0.91

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 26–27 (cleavage; by ctsg)

Ligand- & substrate-binding residues (26): 97; 100; 105; 127; 129; 131; 132; 134; 171; 210; 213; 215 …

Post-translational modifications (16): 2, 5, 21, 27, 34, 37, 41, 58, 136, 239, 312, 19, 214, 214, 257, 332

Disulfide bonds (1): 324–343

Mutagenesis-validated functional residues (3):

Position	Phenotype
27	abolishes secretion and modulation of exocytosis.
34	no effect on secretion and modulation of exocytosis.
45	abolishes secretion and nearly abolishes modulation of exocytosis.

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events
R-HSA-444473	Formyl peptide receptors bind formyl peptides and many other ligands
R-HSA-445355	Smooth Muscle Contraction
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-397014	Muscle contraction
R-HSA-449147	Signaling by Interleukins
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 855 (showing top): BIOCARTA_GCR_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_52, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_WOUND_HEALING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION

GO Biological Process (42): neutrophil homeostasis (GO:0001780), adaptive immune response (GO:0002250), monocyte chemotaxis (GO:0002548), regulation of leukocyte migration (GO:0002685), phagocytosis (GO:0006909), inflammatory response (GO:0006954), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), regulation of cell shape (GO:0008360), myoblast migration involved in skeletal muscle regeneration (GO:0014839), peptide cross-linking (GO:0018149), actin cytoskeleton organization (GO:0030036), keratinocyte differentiation (GO:0030216), positive regulation of vesicle fusion (GO:0031340), regulation of interleukin-1 production (GO:0032652), negative regulation of interleukin-8 production (GO:0032717), positive regulation of interleukin-2 production (GO:0032743), positive regulation of neutrophil apoptotic process (GO:0033031), cellular response to vascular endothelial growth factor stimulus (GO:0035924), positive regulation of T cell proliferation (GO:0042102), neutrophil activation (GO:0042119), negative regulation of apoptotic process (GO:0043066), innate immune response (GO:0045087), positive regulation of T-helper 1 cell differentiation (GO:0045627), negative regulation of T-helper 2 cell differentiation (GO:0045629), negative regulation of exocytosis (GO:0045920), alpha-beta T cell differentiation (GO:0046632), regulation of hormone secretion (GO:0046883), arachidonate secretion (GO:0050482), regulation of inflammatory response (GO:0050727), cellular response to glucocorticoid stimulus (GO:0071385), granulocyte chemotaxis (GO:0071621), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), positive regulation of wound healing (GO:0090303), neutrophil clearance (GO:0097350), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), immune system process (GO:0002376), regulation of cell population proliferation (GO:0042127), negative regulation of transport (GO:0051051)

GO Molecular Function (12): phosphatidylserine binding (GO:0001786), signaling receptor binding (GO:0005102), calcium ion binding (GO:0005509), phospholipid binding (GO:0005543), calcium-dependent phospholipid binding (GO:0005544), lipid binding (GO:0008289), phospholipase A2 inhibitor activity (GO:0019834), calcium-dependent protein binding (GO:0048306), cadherin binding involved in cell-cell adhesion (GO:0098641), phospholipase inhibitor activity (GO:0004859), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (31): cornified envelope (GO:0001533), phagocytic cup (GO:0001891), extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), cell surface (GO:0009986), vesicle membrane (GO:0012506), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), extracellular matrix (GO:0031012), motile cilium (GO:0031514), early endosome membrane (GO:0031901), vesicle (GO:0031982), sarcolemma (GO:0042383), extracellular exosome (GO:0070062), early endosome (GO:0005769), actin filament (GO:0005884), cilium (GO:0005929), endosome membrane (GO:0010008), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Peptide ligand-binding receptors	1
Muscle contraction	1
Signaling by Interleukins	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Immune System	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
plasma membrane	3
phospholipid binding	2
protein binding	2
binding	2
plasma membrane region	2
leukocyte homeostasis	1
myeloid cell homeostasis	1
immune response	1
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
regulation of immune system process	1
regulation of cell migration	1
leukocyte migration	1
endocytosis	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
regulation of cell morphogenesis	1
regulation of biological quality	1
skeletal muscle tissue regeneration	1
myoblast migration	1
protein modification process	1
cytoskeleton organization	1
actin filament-based process	1
epidermal cell differentiation	1
skin development	1
vesicle fusion	1
positive regulation of organelle organization	1
regulation of vesicle fusion	1
positive regulation of transport	1
regulation of cytokine production	1
interleukin-1 production	1
negative regulation of cytokine production	1

Protein interactions and networks

STRING

3688 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANXA1	FPR2	P25090	999
ANXA1	FPR1	P21462	998
ANXA1	S100A11	P31949	993
ANXA1	S100A10	P08206	931
ANXA1	DYSF	O75923	915
ANXA1	FPR3	P25089	892
ANXA1	HSH2D	Q96JZ2	837
ANXA1	YWHAZ	P29213	781
ANXA1	CDH1	P12830	767
ANXA1	S100A6	P06703	739
ANXA1	CALR	P27797	733
ANXA1	TRIM72	Q6ZMU5	703
ANXA1	CTAG1A	P78358	691
ANXA1	TP53	P04637	678
ANXA1	ENO1	P06733	678

IntAct

199 interactions, top by confidence:

A	B	Type	Score
EGFR	ANXA1	psi-mi:“MI:0915”(physical association)	0.770
ANXA1	EGFR	psi-mi:“MI:0915”(physical association)	0.770
ANXA1	EGFR	psi-mi:“MI:0403”(colocalization)	0.770
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NSL1	NDC80	psi-mi:“MI:0914”(association)	0.640
STK4	STRN	psi-mi:“MI:0914”(association)	0.610
ANXA1	LNPK	psi-mi:“MI:0915”(physical association)	0.560
ANXA1	EVA1B	psi-mi:“MI:0915”(physical association)	0.560
ANXA1	ZHX1-C8orf76	psi-mi:“MI:0915”(physical association)	0.560
ANXA1	LEG1	psi-mi:“MI:0915”(physical association)	0.560
sseJ	ANXA1	psi-mi:“MI:0915”(physical association)	0.560
ANXA1	RIPK1	psi-mi:“MI:0915”(physical association)	0.560
ANXA1	IKBKG	psi-mi:“MI:0915”(physical association)	0.560
RIPK1	ANXA1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (382): MEIS2 (Two-hybrid), ANXA1 (Affinity Capture-RNA), ANXA1 (Affinity Capture-RNA), ANXA1 (Affinity Capture-RNA), ANXA1 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS), ANXA1 (Reconstituted Complex), ANXA1 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS), ANXA1 (Affinity Capture-MS)

ESM2 similar proteins: A2SW69, A5A6L7, A5A6M2, A6NMY6, O35639, O35640, P04083, P04272, P07150, P07355, P07356, P08132, P08758, P09525, P10107, P12429, P13214, P13928, P14087, P14669, P14950, P17153, P17785, P19619, P19620, P22464, P24551, P24801, P27006, P46193, P50994, P51662, P55260, P93157, P97429, Q07936, Q2Q1M6, Q3SWX7, Q4R4H7, Q5R1W0

Diamond homologs: A2SW69, A5A6L7, A5A6M2, A6NMY6, C0HJG9, C1L7Y4, C4QH88, O35639, O35640, O76027, O97529, P04083, P04272, P07150, P07355, P07356, P08132, P08133, P08758, P09525, P10107, P12429, P13214, P13928, P14087, P14668, P14669, P14824, P14950, P17153, P17785, P19619, P19620, P20072, P20073, P22464, P22465, P24551, P24639, P24801

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
EGFR	up-regulates	ANXA1	phosphorylation
PRKCA	up-regulates	ANXA1	phosphorylation
PRKCB	up-regulates	ANXA1	phosphorylation
PRKCG	up-regulates	ANXA1	phosphorylation
PRKCH	up-regulates	ANXA1	phosphorylation
SRC	up-regulates	ANXA1	phosphorylation
SRC	unknown	ANXA1	phosphorylation
TRPM7	up-regulates	ANXA1	phosphorylation
ANXA1	“up-regulates activity”	FPR2	binding
ANXA1	“up-regulates activity”	FPR3	binding
ANXA1	“up-regulates activity”	FPR1	binding
SPI1	“down-regulates quantity by repression”	ANXA1	“transcriptional regulation”
ANXA1	up-regulates	Apoptosis
ANXA1	“up-regulates quantity by expression”	IL6	“transcriptional regulation”
ANXA1	“up-regulates quantity by expression”	IL1B	“transcriptional regulation”
ANXA1	“up-regulates quantity by expression”	TNF	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 206 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RIP-mediated NFkB activation via ZBP1	5	23.2×	3e-04
Signaling by ALK	5	19.7×	6e-04
Downstream signal transduction	5	13.1×	2e-03
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	5	12.3×	3e-03
Interleukin-3, Interleukin-5 and GM-CSF signaling	5	10.9×	4e-03
Signaling by high-kinase activity BRAF mutants	5	10.9×	4e-03
Signaling by SCF-KIT	6	10.3×	2e-03
MAP2K and MAPK activation	5	9.8×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
response to muscle stretch	5	21.0×	1e-03
positive regulation of miRNA transcription	7	11.2×	1e-03
obsolete positive regulation of NF-kappaB transcription factor activity	7	7.9×	6e-03
positive regulation of canonical NF-kappaB signal transduction	11	4.4×	7e-03
DNA damage response	13	3.8×	7e-03
intracellular signal transduction	16	3.4×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

93 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	5
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1036 predictions. Top by Δscore:

Variant	Effect	Δscore
9:73158516:TTCCA:T	acceptor_loss	1.0000
9:73158517:TCCA:T	acceptor_loss	1.0000
9:73158518:CCA:C	acceptor_loss	1.0000
9:73158519:CAGAC:C	acceptor_loss	1.0000
9:73158520:A:AG	acceptor_gain	1.0000
9:73158520:A:AT	acceptor_loss	1.0000
9:73158521:G:A	acceptor_loss	1.0000
9:73158521:G:GA	acceptor_gain	1.0000
9:73158521:GA:G	acceptor_gain	1.0000
9:73158521:GAC:G	acceptor_gain	1.0000
9:73158521:GACA:G	acceptor_gain	1.0000
9:73158521:GACAC:G	acceptor_gain	1.0000
9:73158593:GAA:G	donor_gain	1.0000
9:73158599:GTT:G	donor_gain	1.0000
9:73158599:GTTGT:G	donor_loss	1.0000
9:73158600:TT:T	donor_gain	1.0000
9:73158600:TTG:T	donor_loss	1.0000
9:73158601:TG:T	donor_loss	1.0000
9:73158602:G:GA	donor_loss	1.0000
9:73158602:G:GG	donor_gain	1.0000
9:73158603:TAA:T	donor_loss	1.0000
9:73158604:AAG:A	donor_loss	1.0000
9:73158687:A:AG	acceptor_gain	1.0000
9:73158688:T:G	acceptor_gain	1.0000
9:73158693:A:AG	acceptor_gain	1.0000
9:73158694:G:GA	acceptor_gain	1.0000
9:73158694:GC:G	acceptor_gain	1.0000
9:73158694:GCA:G	acceptor_gain	1.0000
9:73158694:GCAA:G	acceptor_gain	1.0000
9:73158694:GCAAA:G	acceptor_gain	1.0000

AlphaMissense

2273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:73159382:C:A	R77S	0.996
9:73165128:G:C	A209P	0.996
9:73159383:G:C	R77P	0.995
9:73165120:T:C	L206S	0.995
9:73165201:T:C	L233P	0.995
9:73165165:T:C	F221S	0.994
9:73167539:T:C	L282P	0.994
9:73160360:T:C	L123P	0.993
9:73163528:C:A	A203D	0.993
9:73169078:G:C	R303P	0.993
9:73158780:T:C	L51S	0.992
9:73162809:T:A	I168K	0.992
9:73163527:G:C	A203P	0.992
9:73166181:T:C	L264P	0.992
9:73167547:G:C	A285P	0.992
9:73160368:G:C	A126P	0.991
9:73165177:T:C	L225P	0.991
9:73160350:G:C	A120P	0.990
9:73162854:T:C	L183P	0.990
9:73163483:G:C	R188P	0.990
9:73165201:T:A	L233H	0.990
9:73167529:G:C	A279P	0.990
9:73159368:G:C	R72P	0.989
9:73160849:G:T	R144I	0.989
9:73165164:T:C	F221L	0.989
9:73165166:C:A	F221L	0.989
9:73165166:C:G	F221L	0.989
9:73169077:C:A	R303S	0.989
9:73160360:T:A	L123H	0.988
9:73162809:T:G	I168R	0.988

dbSNP variants (sampled 300 via entrez): RS1000241754 (9:73170167 A>G), RS1000266047 (9:73154568 A>G), RS1000373649 (9:73153274 A>T), RS1000594415 (9:73153045 A>T), RS1000754947 (9:73166252 C>G,T), RS1000924126 (9:73165627 T>C), RS1001110406 (9:73159871 A>C), RS1001113441 (9:73165526 G>A,T), RS1001121851 (9:73160206 T>G), RS1001313056 (9:73157182 C>A), RS1001370054 (9:73165927 C>G), RS1001411207 (9:73169372 T>C), RS1001588135 (9:73168195 G>T), RS1001600476 (9:73156929 G>A), RS1001780799 (9:73162778 T>C)

Disease associations

OMIM: gene MIM:151690 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000774_4	Schizophrenia, bipolar disorder and depression (combined)	3.000000e-06
GCST002828_22	Urate levels in obese individuals	4.000000e-06
GCST003059_14	Parkinson’s disease	1.000000e-06
GCST007576_7	Chronotype	1.000000e-12
GCST009391_496	Metabolite levels	6.000000e-06
GCST011616_39	Cortical volume	5.000000e-11
GCST011617_24	Cortical surface area	8.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0008328	chronotype measurement
EFO:0005001	phenylalanine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724756 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178677: Inhibition of ANXA1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

145 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	7
Tretinoin	increases expression, increases reaction, decreases expression	6
Cadmium Chloride	decreases expression, increases abundance, increases expression	5
Arsenic Trioxide	increases secretion, increases response to substance, decreases expression, increases expression	4
Cadmium	decreases expression, increases abundance, increases expression	4
Cisplatin	affects response to substance, affects expression, increases expression	4
methylmercuric chloride	increases expression	3
trichostatin A	affects cotreatment, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Doxorubicin	affects expression, decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression, increases metabolic processing	3
Mifepristone	increases phosphorylation, affects binding, decreases reaction, increases reaction, increases localization (+1 more)	3
Aflatoxin B1	affects expression, increases expression	3
bisphenol F	decreases expression, increases expression	2
bisphenol A	decreases expression, increases expression	2
cadmium sulfate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
bisphenol S	decreases expression, increases expression	2
LDN 193189	affects cotreatment, increases expression, decreases expression	2
Air Pollutants	increases abundance, affects expression, affects cotreatment, decreases expression	2
Ascorbic Acid	affects binding, affects cotreatment, increases expression	2
Dexamethasone	increases localization, decreases reaction, increases phosphorylation, decreases response to substance, affects binding (+2 more)	2
Estradiol	decreases expression, increases expression	2
Fluorouracil	affects response to substance, decreases expression	2
Formaldehyde	increases expression	2
Hydrocortisone	affects cotreatment, increases expression, decreases reaction	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	affects cotreatment, increases expression	2

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650895	Binding	Binding affinity to human ANXA1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8BA	Abcam HCT 116 ANXA1 KO	Cancer cell line	Male
CVCL_B8SF	Abcam MCF-7 ANXA1 KO	Cancer cell line	Female
CVCL_B9DD	Abcam A-549 ANXA1 KO	Cancer cell line	Male
CVCL_SC66	HAP1 ANXA1 (-) 1	Cancer cell line	Male
CVCL_SC67	HAP1 ANXA1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.