ANXA2

Summary

ANXA2 (annexin A2, HGNC:537) is a protein-coding gene on chromosome 15q22.2, encoding Annexin A2 (P07355). Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids.

This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. This protein functions as an autocrine factor which heightens osteoclast formation and bone resorption. This gene has three pseudogenes located on chromosomes 4, 9 and 10, respectively. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. Annexin A2 expression has been found to correlate with resistance to treatment against various cancer forms.

Source: NCBI Gene 302 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 50 total
• Druggable target: yes
• MANE Select transcript: NM_004039

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:537
Approved symbol	ANXA2
Name	annexin A2
Location	15q22.2
Locus type	gene with protein product
Status	Approved
Aliases	LIP2
Ensembl gene	ENSG00000182718
Ensembl biotype	protein_coding
OMIM	151740
Entrez	302

Gene structure

Transcript identifiers

Ensembl transcripts: 83 — 68 protein_coding, 6 retained_intron, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000332680, ENST00000396024, ENST00000421017, ENST00000451270, ENST00000504475, ENST00000557904, ENST00000557906, ENST00000557937, ENST00000557986, ENST00000558132, ENST00000558169, ENST00000558503, ENST00000558558, ENST00000558985, ENST00000558986, ENST00000558998, ENST00000559113, ENST00000559176, ENST00000559350, ENST00000559370, ENST00000559467, ENST00000559559, ENST00000559647, ENST00000559725, ENST00000559780, ENST00000559818, ENST00000559956, ENST00000560014, ENST00000560165, ENST00000560367, ENST00000560389, ENST00000560466, ENST00000560468, ENST00000560495, ENST00000560546, ENST00000560936, ENST00000561022, ENST00000561445, ENST00000676687, ENST00000677258, ENST00000677968, ENST00000678061, ENST00000678450, ENST00000678796, ENST00000678870, ENST00000679109, ENST00000861991, ENST00000861992, ENST00000861993, ENST00000861994, ENST00000861995, ENST00000861996, ENST00000861997, ENST00000861998, ENST00000861999, ENST00000862000, ENST00000862001, ENST00000862002, ENST00000862003, ENST00000862004, ENST00000862005, ENST00000862006, ENST00000862007, ENST00000862008, ENST00000862009, ENST00000911891, ENST00000911892, ENST00000911893, ENST00000911894, ENST00000971922, ENST00000971923, ENST00000971924, ENST00000971925, ENST00000971926, ENST00000971927, ENST00000971928, ENST00000971929, ENST00000971930, ENST00000971931, ENST00000971932, ENST00000971933, ENST00000971934, ENST00000971935

RefSeq mRNA: 4 — MANE Select: NM_004039 NM_001002857, NM_001002858, NM_001136015, NM_004039

CCDS: CCDS10175, CCDS32256

Canonical transcript exons

ENST00000451270 — 13 exons

Exon	Start	End
ENSE00002562352	60347151	60347689
ENSE00003547877	60351193	60351251
ENSE00003594061	60382342	60382441
ENSE00003623344	60386028	60386086
ENSE00003664315	60349075	60349197
ENSE00003784124	60364429	60364523
ENSE00003786058	60351724	60351819
ENSE00003786334	60357146	60357236
ENSE00003789166	60360941	60361054
ENSE00003789905	60355919	60355998
ENSE00003791460	60352383	60352476
ENSE00003791499	60354154	60354213
ENSE00003900574	60397943	60397986

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 98.5447 / max 1661.9847, expressed in 1781 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150314	97.3060	1777
150315	0.4605	249
150316	0.3170	161
150311	0.1760	83
150319	0.1307	31
150317	0.1193	12
150318	0.0207	6
150320	0.0094	6
207550	0.0051	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.93	gold quality
cervix squamous epithelium	UBERON:0006922	99.92	gold quality
amniotic fluid	UBERON:0000173	99.90	gold quality
nasal cavity epithelium	UBERON:0005384	99.90	gold quality
epithelium of nasopharynx	UBERON:0001951	99.89	gold quality
cervix epithelium	UBERON:0004801	99.88	gold quality
synovial joint	UBERON:0002217	99.87	gold quality
esophagus squamous epithelium	UBERON:0006920	99.87	gold quality
pharyngeal mucosa	UBERON:0000355	99.86	gold quality
epithelium of bronchus	UBERON:0002031	99.86	gold quality
bronchus	UBERON:0002185	99.86	gold quality
visceral pleura	UBERON:0002401	99.86	gold quality
squamous epithelium	UBERON:0006914	99.86	gold quality
pleura	UBERON:0000977	99.85	gold quality
epithelium of esophagus	UBERON:0001976	99.85	gold quality
parietal pleura	UBERON:0002400	99.85	gold quality
oral cavity	UBERON:0000167	99.83	gold quality
hair follicle	UBERON:0002073	99.83	gold quality
skin of hip	UBERON:0001554	99.82	gold quality
tongue squamous epithelium	UBERON:0006919	99.82	gold quality
islet of Langerhans	UBERON:0000006	99.81	gold quality
palpebral conjunctiva	UBERON:0001812	99.81	gold quality
gingival epithelium	UBERON:0001949	99.81	gold quality
esophagus mucosa	UBERON:0002469	99.81	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.81	gold quality
trigeminal ganglion	UBERON:0001675	99.80	gold quality
gingiva	UBERON:0001828	99.80	gold quality
colonic mucosa	UBERON:0000317	99.79	gold quality
ileal mucosa	UBERON:0000331	99.79	gold quality
mammalian vulva	UBERON:0000997	99.79	gold quality

Single-cell (SCXA)

Detected in 59 experiment(s), a significant marker in 46.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	8318.19
E-GEOD-81547	yes	7412.58
E-ENAD-27	yes	5579.28
E-GEOD-130473	yes	3551.71
E-GEOD-114530	yes	3482.52
E-MTAB-10287	yes	3441.60
E-MTAB-7407	yes	3263.64
E-MTAB-8221	yes	3081.31
E-MTAB-9841	yes	3080.85
E-HCAD-31	yes	2831.66
E-MTAB-9154	yes	2805.23
E-GEOD-124263	yes	2473.80
E-GEOD-93593	yes	2228.30
E-MTAB-6819	yes	2135.32
E-HCAD-1	yes	2077.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CAMTA1, STAT6

miRNA regulators (miRDB)

56 targeting ANXA2, 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-9-5P	100.00	72.28	2361
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514

Literature-anchored findings (GeneRIF, showing 40)

• identification of a hetereotetramer as a plasmin reductase (PMID:11781322)
• amino acids critical for tissue-type plasminogen activator-annexin A2 interaction (PMID:12468550)
• results suggest that annexin II, and, likely, annexin I, may be endogenous suppressors of prostate cancer cell migration and their reduced or lost expression may contribute to prostate cancer development and progression (PMID:12629510)
• virtual Northern blots to analyze expression of NACA and ANX2 in progenitor cultures of nine children with Juvenile myelomonocytic leukemia and five healthy individuals (PMID:12699894)
• analysis of annexin A2 interaction with tissue plasminogen activator, plasminogen, and plasmin (PMID:12730231)
• annexin 2/S100A10 complex functions in the intracellular positioning of recycling endosomes and that both subunits are required for this activity (PMID:13679511)
• annexin II-mediated assembly of plasminogen and t-PA on monocyte/macrophages contributes to plasmin generation, matrix remodeling, and directed migration (PMID:14504107)
• annexin II binds to CEACAM1 in breast neoplasms (PMID:14522961)
• possible mechanistic and regulatory role of Anx-II in prostate cancer progression (PMID:14613585)
• ANXA2 is a Ca(2+)-dependent RNA-binding protein that interacts with the mRNA of the nuclear oncogene, c-myc (PMID:14672933)
• AII does not bind 1,25-D(3) in a physiologically relevant manner (PMID:14991775)
• Western blotting of endothelial cell surface of a number of sites showed higher amounts of tissue plasminogen activator annexin II on cerebral endothelial cell. In contrast, expression of u-PA receptor was the same for all ECs (PMID:14995994)
• Lipocortin II may be a marker or contribute to asthma exacerbation. (PMID:15051937)
• Annexin I serves as both ligand and receptor in promoting phagocytosis. (PMID:15064349)
• E2A-HLF induces annexin II by substituting for cytokines that activate downstream pathways of Ras (PMID:15070701)
• Reduced Annexin 2 expression is associated with osteosarcoma metastases (PMID:15211578)
• Experiments using individual subunits identify annexin 2 as a PtdIns(4,5)P(2)-binding entity (PMID:15226372)
• siRNA-mediated downregulation of annexin A2/S100A10 and disruption of the complex by microinjection of peptide competitors result in a marked reduction in von Willebrand Factor (PMID:15257287)
• Temperature stress-induced annexin 2 translocation is dependent on both expression of protein p11 tyrosine phosphorylation of annexin 2. (PMID:15302870)
• observations suggest a novel pathway for endothelial activation induced by APLA/anti-beta2GPI antibodies that is initiated by cross-linking or clustering of annexin A2 on the endothelial surface (PMID:15471954)
• 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)
• investigation undertaken to identify the significance of annexin II expression and regulation in leukaemia do not fully support the concept of the coagulopathy associated with APL being caused by hyperfibrinolysis alone (PMID:15567461)
• S100A10 and annexin A2 play an important role in plasmin regulation and in cancer cell invasiveness and metastasis [review] (PMID:15574370)
• several single nucleotide polymorphisms in bone morphogenic protein 6, annexin A2, and klotho were associated with sickle cell osteonecrosis (PMID:15784727)
• S100A4 protein alone or in a complex with annexin II accelerated tissue plasminogen activator-mediated plasminogen activation in solution and on the endothelial cell surface (PMID:15788416)
• complex with S100A10 is a substrate of thioredoxin (PMID:15849182)
• AX-II, in addition to inducing GM-CSF expression, increases membrane-bound RANKL synthesis by marrow stromal cells through MAPK-dependent pathway. (PMID:15940368)
• Results show that progression from prostatic intraepithelial neoplasia to prostate cancer is characterized by a reduction of ANX2 and suggest that downregulation of these proteins could represent an important event in prostate carcinogenesis. (PMID:15944914)
• annexin A1 and A2 may have roles in dysferlin deficiency and in muscular dystrophies (PMID:16100712)
• Annexin A2 is part of the putative cell surface vitamin D binding protein binding site complex and functions to mediate the chemotactic cofactor effect. (PMID:16177123)
• analysis of the structural determinant of the PtdIns(4,5)P2 selectivity of A2t (annexin II-p11 heterotetramer), which may be involved in the regulation of PtdIns(4,5)P2 clustering in the cell (PMID:16230353)
• The experimental data suggest that the ANNEXIN A2 gene may relate to cellular apoptosis induced by p53 gene. (PMID:16331566)
• anti-A2 antibodies contribute to the prothrombotic diathesis in antiphospholipid syndrome (PMID:16493010)
• novel gag-binding protein essential for the proper assembly of HIV in monocyte-derived macrophages. (PMID:16501079)
• annexin 2 mediated fibrinolysis on the transitional cell carcinoma cells may play a role in inducing hemorrhagic disorder in vascular intimal carcinomatosis (PMID:16524621)
• Annexin II-dependent localized plasmin generation is associated with angiogenesis and metastasis in breast cancer (PMID:16643892)
• Review discusses a role for annexin 2 in the regulation of ecto-5’-nucleotidase activity, which is dependent upon the stability of the membrane rafts. (PMID:16709165)
• Real-time RT-PCR confirmed up-regulation of IL-8, osteopontin, and TNFRSF14 and down-regulation of SAMeS and CD209 in AH. (PMID:16797773)
• analysis of calcium-dependent heparin binding to annexin A2 (PMID:16882661)
• Results describe the design, production, biophysical characterization and binding properties of a soluble mutant form of annexin A2 domain IV that adopts a partially folded conformation. (PMID:16963080)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	anxa2a	ENSDARG00000003216
danio_rerio	anxa2b	ENSDARG00000053625
mus_musculus	Anxa2	ENSMUSG00000032231
rattus_norvegicus	Anxa2	ENSRNOG00000010362
rattus_norvegicus	AABR07018244.2	ENSRNOG00000058011
drosophila_melanogaster	AnxB9	FBGN0000083
drosophila_melanogaster	AnxB11	FBGN0030749

Paralogs (12): ANXA13 (ENSG00000104537), ANXA10 (ENSG00000109511), ANXA11 (ENSG00000122359), ANXA1 (ENSG00000135046), ANXA7 (ENSG00000138279), ANXA3 (ENSG00000138772), ANXA9 (ENSG00000143412), ANXA5 (ENSG00000164111), ANXA4 (ENSG00000196975), ANXA6 (ENSG00000197043), ANXA8L1 (ENSG00000264230), ANXA8 (ENSG00000265190)

Protein

Protein identifiers

Annexin A2 — P07355 (reviewed: P07355)

Alternative names: Annexin II, Annexin-2, Calpactin I heavy chain, Calpactin-1 heavy chain, Chromobindin-8, Lipocortin II, Placental anticoagulant protein IV, Protein I, p36

All UniProt accessions (24): P07355, A0A024R5Z7, A0A7I2V4P4, H0YKL9, H0YKN4, H0YKS4, H0YKV8, H0YKX9, H0YKZ7, H0YL33, H0YLE2, H0YLV6, H0YM50, H0YMD0, H0YMD9, H0YMM1, H0YMT9, H0YMU9, H0YMW4, H0YN28, H0YN42, H0YNA0, H0YNB8, H0YNP5

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. May be involved in heat-stress response. Inhibits PCSK9-enhanced LDLR degradation, probably reduces PCSK9 protein levels via a translational mechanism but also competes with LDLR for binding with PCSK9. Binds to endosomes damaged by phagocytosis of particulate wear debris and participates in endosomal membrane stabilization, thereby limiting NLRP3 inflammasome activation. Required for endothelial cell surface plasmin generation and may support fibrinolytic surveillance and neoangiogenesis. (Microbial infection) Binds M.pneumoniae CARDS toxin, probably serves as one receptor for this pathogen. When ANXA2 is down-regulated by siRNA, less toxin binds to human cells and less vacuolization (a symptom of M.pneumoniae infection) is seen.

Subunit / interactions. Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36. Interacts with ATP1B1. Interacts with DYSF. Interacts with COCH. Interacts (via repeat Annexin 1) with PCSK9 (via the C-terminal domain); the interaction inhibits the degradation of LDLR. Interacts with CEACAM1 (via the cytoplasmic domain); this interaction is regulated by phosphorylation of CEACAM1. Interacts with APPL2 and APPL1; targets APPL2 to endosomes and acting in parallel to RAB5A. Interacts with S100A4. May interact with UBAP2. Interacts with PLEKHG4B; this interaction is required for PLEKHG4B localization to cell-cell adhesions. (Microbial infection) Interacts with human cytomegalovirus (HCMV). (Microbial infection) Interacts with M.pneumoniae CARDS toxin; CARDS probably uses this protein as a receptor. A portion of internalized CARDS remains associated with intracellular annexin 2.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane. Melanosome.

Post-translational modifications. Phosphorylation of Tyr-24 enhances heat stress-induced translocation to the cell surface. ISGylated.

Disease relevance. Increased expression of ANXA2 is associated with hepatocellular carcinoma tumor progression.

Domain organisation. A pair of annexin repeats may form one binding site for calcium and phospholipid.

Miscellaneous. It may cross-link plasma membrane phospholipids with actin and the cytoskeleton and be involved with exocytosis.

Similarity. Belongs to the annexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P07355-1	1	yes
P07355-2	2

RefSeq proteins (4): NP_001002857, NP_001002858, NP_001129487, NP_004030* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001464	Annexin	Family
IPR002389	ANX2	Family
IPR018252	Annexin_repeat_CS	Conserved_site
IPR018502	Annexin_repeat	Repeat
IPR037104	Annexin_sf	Homologous_superfamily

Pfam: PF00191

UniProt features (60 total): helix 21, modified residue 8, mutagenesis site 8, strand 5, repeat 4, turn 4, sequence conflict 3, cross-link 2, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

41 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2HYV	X-RAY DIFFRACTION	1.42
1W7B	X-RAY DIFFRACTION	1.52
7QQM	X-RAY DIFFRACTION	1.6
7PC5	X-RAY DIFFRACTION	1.7
7P73	X-RAY DIFFRACTION	1.85
2HYU	X-RAY DIFFRACTION	1.86
7ZVN	X-RAY DIFFRACTION	1.87
5LPX	X-RAY DIFFRACTION	1.9
7P74	X-RAY DIFFRACTION	1.9
7PC3	X-RAY DIFFRACTION	1.95
7P70	X-RAY DIFFRACTION	2
7PCB	X-RAY DIFFRACTION	2
2HYW	X-RAY DIFFRACTION	2.1
5LPU	X-RAY DIFFRACTION	2.1
7NMI	X-RAY DIFFRACTION	2.1
7PC7	X-RAY DIFFRACTION	2.1
7EQ7	X-RAY DIFFRACTION	2.11
7P72	X-RAY DIFFRACTION	2.15
8AEL	X-RAY DIFFRACTION	2.2
5N7D	X-RAY DIFFRACTION	2.3
5N7F	X-RAY DIFFRACTION	2.3
6TWX	X-RAY DIFFRACTION	2.3
6TWY	X-RAY DIFFRACTION	2.3
7PC4	X-RAY DIFFRACTION	2.3
6TWU	X-RAY DIFFRACTION	2.4
7PC9	X-RAY DIFFRACTION	2.4
7ZVX	X-RAY DIFFRACTION	2.4
7QQL	X-RAY DIFFRACTION	2.44
7QQN	X-RAY DIFFRACTION	2.45
7PC8	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07355-F1	94.59	0.92

Functional residue map

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

Post-translational modifications (10): 49, 152, 184, 199, 227, 49, 49, 2, 24, 26

Mutagenesis-validated functional residues (8):

Position	Phenotype
24	abolishes heat stress-induced cell surface localization.
26	stronger interaction with s100a4.
28–36	no effect on interaction with pcsk9.
37–47	slightly decreases interaction with pcsk9.
77–81	strongly decreases interaction with pcsk9.
77–80	decreases interaction with pcsk9. strongly decreases interaction with pcsk9; when associated with k-88.
80–84	no effect on interaction with pcsk9.
88	strongly decreases interaction with pcsk9; when associated with 77-a–a-80.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-445355	Smooth Muscle Contraction
R-HSA-6798695	Neutrophil degranulation
R-HSA-75205	Dissolution of Fibrin Clot
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-397014	Muscle contraction
R-HSA-447115	Interleukin-12 family signaling
R-HSA-449147	Signaling by Interleukins
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9020591	Interleukin-12 signaling
R-HSA-9855142	Cellular responses to mechanical stimuli
R-HSA-9860931	Response of endothelial cells to shear stress

MSigDB gene sets: 746 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, MODULE_52, SHEPARD_BMYB_MORPHOLINO_UP, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_VESICLE_FUSION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_VACUOLE_ORGANIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT

GO Biological Process (28): angiogenesis (GO:0001525), membrane raft assembly (GO:0001765), positive regulation of receptor recycling (GO:0001921), negative regulation of receptor internalization (GO:0002091), vesicle budding from membrane (GO:0006900), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), positive regulation of plasminogen activation (GO:0010756), response to activity (GO:0014823), collagen fibril organization (GO:0030199), lung development (GO:0030324), positive regulation of vesicle fusion (GO:0031340), negative regulation of low-density lipoprotein particle receptor catabolic process (GO:0032804), osteoclast development (GO:0036035), fibrinolysis (GO:0042730), mRNA transcription by RNA polymerase II (GO:0042789), positive regulation of vacuole organization (GO:0044090), positive regulation of exocytosis (GO:0045921), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of neurogenesis (GO:0050767), epithelial cell apoptotic process (GO:1904019), positive regulation of low-density lipoprotein particle clearance (GO:1905581), positive regulation of receptor-mediated endocytosis involved in cholesterol transport (GO:1905602), positive regulation of plasma membrane repair (GO:1905686), negative regulation of coagulation (GO:0050819), negative regulation of transport (GO:0051051), positive regulation of multicellular organismal process (GO:0051240), cell-cell adhesion (GO:0098609)

GO Molecular Function (15): phosphatidylserine binding (GO:0001786), protease binding (GO:0002020), RNA binding (GO:0003723), serine-type endopeptidase inhibitor activity (GO:0004867), calcium ion binding (GO:0005509), calcium-dependent phospholipid binding (GO:0005544), phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), cytoskeletal protein binding (GO:0008092), phospholipase A2 inhibitor activity (GO:0019834), identical protein binding (GO:0042802), S100 protein binding (GO:0044548), calcium-dependent protein binding (GO:0048306), cadherin binding involved in cell-cell adhesion (GO:0098641), phospholipase inhibitor activity (GO:0004859), protein binding (GO:0005515)

GO Cellular Component (33): cornified envelope (GO:0001533), extracellular region (GO:0005576), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), endosome (GO:0005768), early endosome (GO:0005769), lipid droplet (GO:0005811), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), cell surface (GO:0009986), vesicle membrane (GO:0012506), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), nuclear matrix (GO:0016363), midbody (GO:0030496), extracellular matrix (GO:0031012), late endosome membrane (GO:0031902), vesicle (GO:0031982), azurophil granule lumen (GO:0035578), myelin sheath adaxonal region (GO:0035749), sarcolemma (GO:0042383), melanosome (GO:0042470), Schmidt-Lanterman incisure (GO:0043220), extracellular exosome (GO:0070062), RNA polymerase II transcription regulator complex (GO:0090575), plasma membrane protein complex (GO:0098797), AnxA2-p11 complex (GO:1990665), PCSK9-AnxA2 complex (GO:1990667), membrane raft (GO:0045121)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Immune System	2
Muscle contraction	1
Innate Immune System	1
Hemostasis	1
Interleukin-12 signaling	1
Response of endothelial cells to shear stress	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Signaling by Interleukins	1
Cytokine Signaling in Immune system	1
Interleukin-12 family signaling	1
Cellular responses to stimuli	1
Cellular responses to mechanical stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
protein binding	4
positive regulation of organelle organization	2
transcription by RNA polymerase II	2
phospholipid binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
membrane raft organization	1
membrane assembly	1
receptor recycling	1
regulation of receptor recycling	1
positive regulation of macromolecule metabolic process	1
positive regulation of signaling	1
regulation of receptor internalization	1
receptor internalization	1
negative regulation of receptor-mediated endocytosis	1
vesicle organization	1
vesicle-mediated transport	1
membrane organization	1
cellular process	1
cell-substrate adhesion	1
regulation of plasminogen activation	1
positive regulation of protein processing	1
plasminogen activation	1
response to stimulus	1
extracellular matrix organization	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
vesicle fusion	1
regulation of vesicle fusion	1
positive regulation of transport	1
low-density lipoprotein particle receptor catabolic process	1
regulation of low-density lipoprotein particle receptor catabolic process	1
negative regulation of protein catabolic process	1
negative regulation of receptor catabolic process	1
osteoclast differentiation	1
myeloid cell development	1
bone cell development	1
negative regulation of blood coagulation	1

Protein interactions and networks

STRING

3840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANXA2	S100A10	P08206	999
ANXA2	ANXA2R	Q3ZCQ2	997
ANXA2	PLG	P00747	996
ANXA2	PLAT	P00750	994
ANXA2	S100A11	P31949	991
ANXA2	S100A4	P26447	987
ANXA2	CD63	P08962	982
ANXA2	TLR4	O00206	967
ANXA2	AHNAK	Q09666	966
ANXA2	CTSB	P07858	952
ANXA2	S100A1	P23297	947
ANXA2	DYSF	O75923	944
ANXA2	APOH	P02749	922
ANXA2	CALR	P27797	915
ANXA2	MYC	P01106	915
ANXA2	S100A6	P06703	915

IntAct

336 interactions, top by confidence:

A	B	Type	Score
p37	ANXA2	psi-mi:“MI:0407”(direct interaction)	0.780
p37	ANXA2	psi-mi:“MI:0403”(colocalization)	0.780
p37	ANXA2	psi-mi:“MI:0915”(physical association)	0.780
ANXA2	p37	psi-mi:“MI:0915”(physical association)	0.780
WFDC2	ANXA2	psi-mi:“MI:0914”(association)	0.740
WFDC2	ANXA2	psi-mi:“MI:0915”(physical association)	0.740
WFDC2	ANXA2	psi-mi:“MI:0403”(colocalization)	0.740

BioGRID (562): ANXA2 (Affinity Capture-Western), ANXA2 (Affinity Capture-Western), PLA2G4A (Affinity Capture-Western), ANXA2 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), S100A10 (Affinity Capture-MS), ANXA13 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), ANXA2 (Affinity Capture-Western), ANXA2 (Co-fractionation)

ESM2 similar proteins: A2SW69, A5A6L7, A6NMY6, O35639, O35640, O97529, P04272, P07355, P07356, P08132, P08758, P09525, P12429, P13214, P13928, P14668, P14669, P14824, P14950, P17153, P17785, P19620, P22464, P24551, P24801, P26256, P27006, P27216, P48036, P50994, P51074, P55260, P70075, P81287, P93157, P97429, Q07936, Q29471, Q2Q1M6, Q3SWX7

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

6 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	ANXA2	phosphorylation
PRKCA	unknown	ANXA2	phosphorylation
UBAP2	“down-regulates quantity”	ANXA2	ubiquitination
CBLL1	“down-regulates quantity by destabilization”	ANXA2	ubiquitination
YES1	“up-regulates activity”	ANXA2	phosphorylation
PRKCB	unknown	ANXA2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 124 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
RHO GTPases activate PAKs	6	37.9×	6e-06
Signaling by high-kinase activity BRAF mutants	5	18.4×	2e-03
MAP2K and MAPK activation	5	16.6×	2e-03
Signaling by moderate kinase activity BRAF mutants	5	14.8×	2e-03
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	14.8×	2e-03
Signaling downstream of RAS mutants	5	14.8×	2e-03
FCGR3A-mediated phagocytosis	5	10.9×	5e-03
Regulation of actin dynamics for phagocytic cup formation	5	10.7×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
epidermal growth factor receptor signaling pathway	6	14.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1868 predictions. Top by Δscore:

Variant	Effect	Δscore
15:60347701:C:CT	acceptor_gain	1.0000
15:60347701:C:T	acceptor_gain	1.0000
15:60347702:A:T	acceptor_gain	1.0000
15:60349194:TGCC:T	acceptor_gain	1.0000
15:60349196:CC:C	acceptor_gain	1.0000
15:60349197:CC:C	acceptor_gain	1.0000
15:60349198:C:CA	acceptor_loss	1.0000
15:60349198:C:CC	acceptor_gain	1.0000
15:60351187:CCTTA:C	donor_loss	1.0000
15:60351188:CTTA:C	donor_loss	1.0000
15:60351189:TTAC:T	donor_loss	1.0000
15:60351190:TA:T	donor_loss	1.0000
15:60351192:C:A	donor_loss	1.0000
15:60351247:CTGAA:C	acceptor_gain	1.0000
15:60351248:TGAA:T	acceptor_gain	1.0000
15:60351249:GAA:G	acceptor_gain	1.0000
15:60351250:AA:A	acceptor_gain	1.0000
15:60351251:AC:A	acceptor_loss	1.0000
15:60351252:C:CC	acceptor_gain	1.0000
15:60351252:CT:C	acceptor_loss	1.0000
15:60351253:T:G	acceptor_loss	1.0000
15:60351718:ACTT:A	donor_loss	1.0000
15:60351719:CTTA:C	donor_loss	1.0000
15:60351722:A:AC	donor_gain	1.0000
15:60351722:AC:A	donor_gain	1.0000
15:60351722:ACC:A	donor_gain	1.0000
15:60351723:C:CA	donor_loss	1.0000
15:60351723:C:CC	donor_gain	1.0000
15:60351723:CC:C	donor_gain	1.0000
15:60351723:CCC:C	donor_gain	1.0000

AlphaMissense

2234 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:60364468:T:A	R68S	1.000
15:60364468:T:G	R68S	1.000
15:60349114:G:C	F307L	0.999
15:60349114:G:T	F307L	0.999
15:60349116:A:G	F307L	0.999
15:60349151:C:G	R295P	0.999
15:60351209:A:G	L274P	0.999
15:60351218:G:T	A271D	0.999
15:60351219:C:G	A271P	0.999
15:60352391:A:G	L225P	0.999
15:60352428:A:G	W213R	0.999
15:60352428:A:T	W213R	0.999
15:60352460:C:T	G202E	0.999
15:60352461:C:G	G202R	0.999
15:60352461:C:T	G202R	0.999
15:60352472:A:G	L198P	0.999
15:60354158:G:T	A195D	0.999
15:60357190:C:A	R135I	0.999
15:60357211:A:G	L128P	0.999
15:60360957:A:G	L114P	0.999
15:60360993:A:G	L102P	0.999
15:60364469:C:G	R68T	0.999
15:60347645:A:C	C335W	0.998
15:60347646:C:T	C335Y	0.998
15:60347647:A:G	C335R	0.998
15:60347658:A:G	L331P	0.998
15:60349079:A:T	I319N	0.998
15:60349115:A:G	F307S	0.998
15:60349140:C:G	D299H	0.998
15:60349152:G:T	R295S	0.998

dbSNP variants (sampled 300 via entrez): RS1000136534 (15:60389152 G>A), RS1000137430 (15:60394062 C>G,T), RS1000209964 (15:60357581 C>T), RS1000246171 (15:60354719 G>T), RS1000263989 (15:60357376 A>G), RS1000291029 (15:60364487 T>A,C), RS1000387311 (15:60383720 AC>A,ACC,ACCCCCC,ACCCCCCCCC), RS1000419213 (15:60359433 C>G,T), RS1000470546 (15:60362334 C>G), RS1000545564 (15:60395134 G>C), RS1000545929 (15:60356374 T>C), RS1000651601 (15:60366481 G>A,C), RS1000704495 (15:60399806 G>A), RS1000760627 (15:60360434 G>C), RS1000821359 (15:60362639 A>G)

Disease associations

OMIM: gene MIM:151740 | 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
GCST002560_12	Type 2 diabetes	7.000000e-06
GCST002560_20	Type 2 diabetes	7.000000e-06
GCST003542_185	Night sleep phenotypes	2.000000e-06
GCST006585_1721	Blood protein levels	2.000000e-10
GCST007994_14	Asthma (age of onset)	5.000000e-06
GCST007995_44	Asthma (childhood onset)	3.000000e-15
GCST009798_17	Asthma	2.000000e-19

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1764938 (SINGLE PROTEIN), CHEMBL2111435 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

57 potent at pChembl≥5 of 121 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.92	IC50	1200	nM	CHEMBL3334803
5.92	IC50	1202	nM	CHEMBL3334803
5.75	IC50	1800	nM	CHEMBL1766592
5.68	IC50	2100	nM	CHEMBL1766591
5.57	IC50	2692	nM	CHEMBL1766727
5.54	IC50	2884	nM	CHEMBL1766718
5.52	IC50	3000	nM	CHEMBL1766718
5.52	IC50	3000	nM	CHEMBL1766727
5.41	IC50	3890	nM	CHEMBL1766609
5.40	IC50	4000	nM	CHEMBL3334808
5.40	IC50	4000	nM	CHEMBL3334844
5.40	IC50	4000	nM	CHEMBL1766609
5.35	IC50	4467	nM	CHEMBL3334844
5.35	IC50	4467	nM	CHEMBL3334808
5.31	IC50	4898	nM	CHEMBL1766736
5.30	IC50	5000	nM	CHEMBL1766736
5.22	IC50	6000	nM	CHEMBL1766606
5.22	IC50	6000	nM	CHEMBL1766719
5.22	IC50	6000	nM	CHEMBL1766730
5.20	IC50	6310	nM	CHEMBL1766606
5.20	IC50	6310	nM	CHEMBL1766730
5.19	IC50	6457	nM	CHEMBL1766719
5.16	IC50	7000	nM	CHEMBL3334812
5.16	IC50	7000	nM	CHEMBL3334839
5.16	IC50	7000	nM	CHEMBL3334846
5.16	IC50	7000	nM	CHEMBL1766713
5.16	IC50	7000	nM	CHEMBL1766723
5.16	IC50	7000	nM	CHEMBL1766724
5.16	IC50	6918	nM	CHEMBL1766713
5.16	IC50	6918	nM	CHEMBL1766723
5.15	IC50	7079	nM	CHEMBL1766724
5.14	IC50	7244	nM	CHEMBL3334846
5.14	IC50	7244	nM	CHEMBL3334812
5.13	IC50	7413	nM	CHEMBL3334839
5.12	IC50	7586	nM	CHEMBL1766608
5.12	IC50	7586	nM	CHEMBL1766714
5.12	IC50	7586	nM	CHEMBL1766717
5.10	IC50	8000	nM	CHEMBL3334842
5.10	IC50	8000	nM	CHEMBL3334845
5.10	IC50	8000	nM	CHEMBL1766607
5.10	IC50	8000	nM	CHEMBL1766608
5.10	IC50	8000	nM	CHEMBL1766714
5.10	IC50	8000	nM	CHEMBL1766717
5.08	IC50	8318	nM	CHEMBL3334842
5.08	IC50	8318	nM	CHEMBL1766607
5.07	IC50	8511	nM	CHEMBL3334845
5.06	IC50	8800	nM	CHEMBL1766587
5.05	IC50	8913	nM	CHEMBL3334810
5.05	IC50	9000	nM	CHEMBL3334810
5.05	IC50	9000	nM	CHEMBL1766605

PubChem BioAssay actives

57 with measured affinity, of 213 total; 30 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
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylsulfanylbutanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-6-aminohexanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]pentanedioic acid	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	1.2000	uM
4-[3-[3-(4-aminophenyl)sulfanylphenyl]sulfonylphenyl]sulfanylaniline	592541: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by FRET assay	ic50	1.8000	uM
5-benzyl-4-methyl-2-[(4-methylphenyl)sulfonylamino]thiophene-3-carboxamide	592541: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by FRET assay	ic50	2.1000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-1-(2-hydroxypropyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	2.6915	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(3-methoxypropyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	2.8840	uM
(4E)-5-[3,5-bis(trifluoromethyl)phenyl]-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	3.8904	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(furan-2-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]-N-(4-propan-2-ylphenyl)acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	4.0000	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(4-methoxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(trifluoromethyl)phenyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	4.0000	uM
(4E)-4-[(2-ethoxyphenyl)-hydroxymethylidene]-5-[3-fluoro-4-(trifluoromethyl)phenyl]-1-(3-methoxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	4.8978	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)-5-[4-(trifluoromethyl)phenyl]pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.0000	uM
(4E)-4-[(4-chlorophenyl)-hydroxymethylidene]-1-prop-2-enyl-5-[4-(trifluoromethyl)phenyl]pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.0000	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-5-(4-propan-2-ylphenyl)-1-prop-2-enylpyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.0000	uM
(4E)-5-(3,5-dichlorophenyl)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.9183	uM
(4E)-4-[hydroxy-(3-methoxyphenyl)methylidene]-1-(2-hydroxypropyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	6.9183	uM
N-(4-bromophenyl)-2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(furan-2-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	7.0000	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(3-methoxypropyl)-1,2,4-triazol-3-yl]sulfanyl]-N-(4-propan-2-ylphenyl)acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	7.0000	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(4-methoxyphenyl)-1,2,4-triazol-3-yl]sulfanyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	7.0000	uM
(4E)-4-[(2-ethoxyphenyl)-hydroxymethylidene]-1-(2-hydroxypropyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	7.0000	uM
(4E)-5-[2,4-bis(trifluoromethyl)phenyl]-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	7.5858	uM
(4E)-5-[4-chloro-3-(trifluoromethyl)phenyl]-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	7.5858	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-methoxyethyl)-5-(4-propan-2-ylphenyl)pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	7.5858	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-prop-2-enyl-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(trifluoromethyl)phenyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	8.0000	uM
2-[[4-(4-chlorophenyl)-5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(trifluoromethyl)phenyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	8.0000	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)-5-[3-(trifluoromethyl)phenyl]pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	8.0000	uM
N-(2,5-dimethylphenyl)-2-[4-[(E)-3-phenylprop-2-enyl]piperazin-1-yl]acetamide	592541: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by FRET assay	ic50	8.8000	uM
N-[3,5-bis(trifluoromethyl)phenyl]-2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(furan-2-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	8.9125	uM
(4E)-4-[hydroxy-(4-methylphenyl)methylidene]-1-(2-hydroxypropyl)-5-[4-(trifluoromethoxy)phenyl]pyrrolidine-2,3-dione	592542: Inhibition of Cy3-labeled annexin A2(1-14)-Cy5- labeled S100A10 interaction after 5 mins by counterscreen assay	ic50	9.0000	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(3-methoxypropyl)-1,2,4-triazol-3-yl]sulfanyl]-N-[4-(trifluoromethyl)phenyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	9.5499	uM
N-(3,4-dimethylphenyl)-2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-(furan-2-ylmethyl)-1,2,4-triazol-3-yl]sulfanyl]acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	9.5499	uM
2-[[5-[(4,6-dimethylpyrimidin-2-yl)sulfanylmethyl]-4-prop-2-enyl-1,2,4-triazol-3-yl]sulfanyl]-N-(4-propan-2-ylphenyl)acetamide	1162040: Inhibition of Annexin A2 N-terminus/Protein S100-A10 (unknown origin) protein interaction pre-incubated for 5 mins by FRET assay	ic50	9.7724	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
Tretinoin	affects localization, decreases expression	8
bisphenol A	decreases expression, increases expression	6
Arsenic Trioxide	increases degradation, increases expression, decreases response to substance, affects localization, decreases expression	6
trichostatin A	affects cotreatment, increases expression	4
Vorinostat	affects cotreatment, affects expression, increases expression	3
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases metabolic processing	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
mercuric bromide	affects cotreatment, increases expression	2
2,3-dimethoxy-1,4-naphthoquinone	increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Resveratrol	increases expression	2
Decitabine	affects cotreatment, affects expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Arsenic	decreases expression, increases abundance, affects expression	2
Cadmium	increases expression	2
Cytarabine	decreases expression, increases expression	2
Lead	affects binding, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
1-Methyl-4-phenylpyridinium	affects expression, increases expression	2
Cadmium Chloride	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
potassium perchlorate	decreases expression	1
titanium dioxide	decreases phosphorylation	1

ChEMBL screening assays

34 unique, capped per target: 34 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1226139	Binding	Induction of annexin-2-mediated cytotoxicity in human CHP100 cells at 4 uM after 2 hrs by MTT assay	Actin microfilament aggregation induced by withaferin A is mediated by annexin II. — Nat Chem Biol

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1V9	Abcam A-549 ANXA2 KO	Cancer cell line	Male
CVCL_D1ZW	Abcam HCT 116 ANXA2 KO	Cancer cell line	Male
CVCL_D2N4	Abcam THP-1 ANXA2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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