MTA1

Summary

MTA1 (metastasis associated 1, HGNC:7410) is a protein-coding gene on chromosome 14q32.33, encoding Metastasis-associated protein MTA1 (Q13330). Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator.

This gene encodes a protein that was identified in a screen for genes expressed in metastatic cells, specifically, mammary adenocarcinoma cell lines. Expression of this gene has been correlated with the metastatic potential of at least two types of carcinomas although it is also expressed in many normal tissues. The role it plays in metastasis is unclear. It was initially thought to be the 70kD component of a nucleosome remodeling deacetylase complex, NuRD, but it is more likely that this component is a different but very similar protein. These two proteins are so closely related, though, that they share the same types of domains. These domains include two DNA binding domains, a dimerization domain, and a domain commonly found in proteins that methylate DNA. The profile and activity of this gene product suggest that it is involved in regulating transcription and that this may be accomplished by chromatin remodeling. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9112 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 121 total
• Druggable target: yes
• Transcription factor: yes — 57 downstream targets (CollecTRI)
• MANE Select transcript: NM_004689

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7410
Approved symbol	MTA1
Name	metastasis associated 1
Location	14q32.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182979
Ensembl biotype	protein_coding
OMIM	603526
Entrez	9112

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 14 protein_coding, 10 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000331320, ENST00000405646, ENST00000406191, ENST00000424723, ENST00000426567, ENST00000434050, ENST00000435036, ENST00000438610, ENST00000469140, ENST00000481012, ENST00000481206, ENST00000481635, ENST00000490198, ENST00000494026, ENST00000494981, ENST00000498644, ENST00000550551, ENST00000550808, ENST00000551236, ENST00000552286, ENST00000885745, ENST00000885746, ENST00000885747, ENST00000885748, ENST00000885749, ENST00000885750, ENST00000939530, ENST00000939531, ENST00000939532

RefSeq mRNA: 4 — MANE Select: NM_004689 NM_001203258, NM_001411061, NM_001411062, NM_004689

CCDS: CCDS32169, CCDS55954, CCDS91956, CCDS91957

Canonical transcript exons

ENST00000331320 — 21 exons

Exon	Start	End
ENSE00001554009	105470065	105470729
ENSE00001878978	105419827	105420063
ENSE00003478243	105449359	105449409
ENSE00003479101	105464416	105464567
ENSE00003502253	105466426	105466578
ENSE00003521457	105438672	105438739
ENSE00003526520	105469467	105469498
ENSE00003536638	105465094	105465183
ENSE00003540550	105454193	105454310
ENSE00003569467	105460358	105460457
ENSE00003572859	105463493	105463551
ENSE00003593969	105466707	105466742
ENSE00003600351	105445418	105445511
ENSE00003608499	105469841	105469992
ENSE00003643605	105464674	105464863
ENSE00003645191	105464032	105464147
ENSE00003646154	105460765	105460953
ENSE00003648245	105458270	105458372
ENSE00003679098	105450058	105450184
ENSE00003679501	105450261	105450324
ENSE00003685584	105463184	105463258

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.2903 / max 348.3474, expressed in 1805 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141893	38.7500	1805
141895	0.8095	492
141896	0.6361	373
141894	0.5575	325
141898	0.4920	251
141903	0.4452	253
141900	0.3738	49
141901	0.1372	36
141902	0.0889	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.65	gold quality
right lobe of thyroid gland	UBERON:0001119	98.51	gold quality
left lobe of thyroid gland	UBERON:0001120	98.28	gold quality
metanephros cortex	UBERON:0010533	98.16	gold quality
apex of heart	UBERON:0002098	98.15	gold quality
endometrium epithelium	UBERON:0004811	98.08	gold quality
right ovary	UBERON:0002118	97.99	gold quality
left ovary	UBERON:0002119	97.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.88	gold quality
endocervix	UBERON:0000458	97.75	gold quality
left uterine tube	UBERON:0001303	97.75	gold quality
adenohypophysis	UBERON:0002196	97.72	gold quality
body of uterus	UBERON:0009853	97.66	gold quality
cerebellar hemisphere	UBERON:0002245	97.56	gold quality
cerebellar cortex	UBERON:0002129	97.51	gold quality
thyroid gland	UBERON:0002046	97.45	gold quality
pituitary gland	UBERON:0000007	97.41	gold quality
tibial nerve	UBERON:0001323	97.36	gold quality
ganglionic eminence	UBERON:0004023	97.31	gold quality
mucosa of stomach	UBERON:0001199	97.27	gold quality
minor salivary gland	UBERON:0001830	97.24	gold quality
lower esophagus mucosa	UBERON:0035834	97.20	gold quality
corpus epididymis	UBERON:0004359	97.19	gold quality
right atrium auricular region	UBERON:0006631	97.18	gold quality
ectocervix	UBERON:0012249	97.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.99	gold quality
body of pancreas	UBERON:0001150	96.97	gold quality
heart left ventricle	UBERON:0002084	96.95	gold quality
ventricular zone	UBERON:0003053	96.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.90	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.21
E-HCAD-1	yes	8.50
E-HCAD-5	no	2.23

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

57 targets.

Target	Regulation
ALOX15	Unknown
BCAS3	Activation
BCL2L1	Activation
BLOC1S1
BMAL1
BRCA1	Unknown
CDH1	Repression
CDH17
CDKN1A	Repression
CDKN2A	Activation
CLOCK
COP1
CRY1
CXCL1	Activation
CXCL2
EGFR	Activation
EHMT2
EPHA2	Repression
ESR1	Repression
FASLG
GNAI2	Unknown
HDAC1	Unknown
HIF1A	Activation
HMMR	Unknown
IL1B
ITGB3BP	Unknown
LMO4
MIR661
MMP9	Unknown
MNAT1	Unknown

Upstream regulators (CollecTRI, top): BMAL1, CLOCK, IFI16, LMO4, MTA1, NRG1, PARP1, SMAD7, SNAI1, SP1, TP53

miRNA regulators (miRDB)

93 targeting MTA1, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
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-548AR-5P	99.94	71.28	3515
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

Literature-anchored findings (GeneRIF, showing 40)

• expression is closely related to invasiveness and metastasis in non-small-cell lung carcinoma (PMID:11804687)
• metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes (PMID:11948399)
• naturally occurring short form that contains a previously unknown sequence of 33 amino acids with an ER-binding motif, Leu-Arg-Ile-Leu-Leu (LRILL); MTA1s localizes in the cytoplasm, sequesters ER in the cytoplasm, and enhances non-genomic responses of ER (PMID:12167865)
• MTA1 binds to the MMP-9 promoter, thereby repressing expression of this type IV collagenase via histone-dependent and independent mechanisms (PMID:12431981)
• interaction with MAT1 and regulation of estrogen receptor transactivation functions (PMID:12527756)
• The results suggest that the MTA1 protein may serve multiple functions in cellular signaling, chromosome remodeling and transcription processes that are important in the progression, invasion and growth of metastatic epithelial cells. (PMID:12650603)
• High expression of the MTA1 gene is associated with hepatocellular carcinoma (PMID:12684630)
• MTA1 and MTA2 repress transcription specifically, are located in the nucleus, and contain associated histone deacetylase activity; MTA1 associates with a different set of transcription factors from MTA2 (PMID:12920132)
• enhanced expression of MTA1 promotes the acquisition of an invasive, metastatic phenotype, and thus enhances the malignancy of pancreatic adenocarcinoma cells by modulation of the cytoskeleton (PMID:14735193)
• This study identified an association of MTA1 expression and prostate cancer progression. (PMID:14871807)
• MTA1s interacts with CKI-gamma2 in vitro and in vivo and colocalizes in the cytoplasm (PMID:15077195)
• overexpression of MTA1 protein and acetylation level of histone H4 protein are closely related (PMID:15095300)
• Metastasis-associated protein 1 interacts with NRIF3, an estrogen-inducible nuclear receptor coregulator (PMID:15254226)
• MTA1 is one of the first downstream targets of c-MYC function that are essential for the transformation potential of c-MYC. (PMID:16172399)
• MTA1 overexpression is associated with high recurrence of breast cancer (PMID:16244788)
• role for MTA1-BCAS3 pathway in promoting cancerous phenotypes in breast tumor cells (PMID:16617102)
• Overexpression of the MTA1 gene correlates with lymph node metastasis of carcinomas of the larynx. (PMID:16646402)
• structure and antiestrogenic activity of the unique C-terminal, NR-box motif-containing region of MTA1 (PMID:16807247)
• These studies demonstrate that MTA1 is expressed in both benign and malignant neoplasms. While its expression is associated with tissue invasion it may not be sufficient for the progression of neoplasms to metastatic stages. (PMID:16831056)
• BCAS3 overexpression in hormone receptor-positive premenopausal breast cancer seemed to be associated with impaired responses to tamoxifen (PMID:16855396)
• MTA1 enhances angiogenesis by stabilization of the HIF-1alpha protein, which is closely related to the increased metastatic potential of cancer cells with high MTA1 expression (PMID:16969516)
• role for the MTA1 as an upstream modifier of Six3 and indicate that Six3 is a direct stimulator of rhodopsin expression. (PMID:17666527)
• Results suggest that MTA1 promotes the metastatic ability of B16F10 cancer cells. (PMID:17868030)
• These findings strongly implicate MTA1 in the transcriptional repression of BRCA1 leading to abnormal centrosome number and chromosomal instability. (PMID:17922032)
• study shows HSF1 binds to MTA1 in vitro & in breast carcinoma; repression of estrogen-dependent transcription may contribute to role of HSF1 in cancer (PMID:17922035)
• MTA1 expression was significantly higher in noninvasive breast cancer cell lines than in invasive ones. (PMID:18196870)
• MTA1 is closely associated with microvascular invasion, frequent postoperative recurrence, and poor survival of HCC patients, especially in those with HBV-associated HCC. (PMID:18306220)
• HIF-1alpha expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma (PMID:18362831)
• Histologically, MTA1 protein production was strongly associated with cancer cell invasion, and clinically there was a correlation between lymph node metastasis and MTA1 protein production. (PMID:18640824)
• MTA1 is up-regulated in advanced ovarian cancer, represses ERbeta, and enhances expression of GRO. (PMID:18719363)
• This study was undertaken to explore the potential role of MTA1 in mouse liver. (PMID:18769059)
• the high expression level of MTA proteins in human chorionic cells might facilitate trophoblast cell migration and neoangiogenesis (PMID:19363681)
• ezrin and metastatic tumor antigen positivity can be additional prognostic markers in osteosarcoma of the jaw. (PMID:19366061)
• Metastasis-associated gene 1 expression is significantly associated with malignant behavior in pancreatic endocrine tumors. (PMID:19377441)
• MTA1 may promote lung carcinogenesis by enhancing HIF-1alpha protein activity. (PMID:19403384)
• Results suggest that miR-661 be further investigated for therapeutic use in down-regulating the expression of MTA1 in cancer cells. (PMID:19584269)
• MTA1 is required for optimum DNA double-strand break repair after ionizing radiation. (PMID:19805145)
• there is a p53-independent function of MTA1 in DNA damage response via modulation of the p21 WAF1-proliferating cell nuclear antigen pathway (PMID:20071335)
• Findings suggest that, in addition to its role in the repair of double strand breaks caused by ionizing radiation, MTA1 also participates in the UV-induced ATR-mediated DNA damage checkpoint pathway. (PMID:20427275)
• identify MTA1, a subunit of the NuRD complex, as a new HIC1 corepressor. (PMID:20547755)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mta1	ENSDARG00000007198
mus_musculus	Mta1	ENSMUSG00000021144
rattus_norvegicus	Mta1	ENSRNOG00000004711
drosophila_melanogaster	MTA1-like	FBGN0027951

Paralogs (5): MTA3 (ENSG00000057935), MIER2 (ENSG00000105556), MTA2 (ENSG00000149480), MIER3 (ENSG00000155545), MIER1 (ENSG00000198160)

Protein

Protein identifiers

Metastasis-associated protein MTA1 — Q13330 (reviewed: Q13330)

All UniProt accessions (6): Q13330, E7ESY4, F8W9Y9, H0Y4T7, H0YIT0, H7C3F3

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. In the NuRD complex, regulates transcription of its targets by modifying the acetylation status of the target chromatin and cofactor accessibility to the target DNA. In conjunction with other components of NuRD, acts as a transcriptional corepressor of BRCA1, ESR1, TFF1 and CDKN1A. Acts as a transcriptional coactivator of BCAS3, and SUMO2, independent of the NuRD complex. Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3. Regulates p53-dependent and -independent DNA repair processes following genotoxic stress. Regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2 thereby regulating the p53-dependent DNA repair. Plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light and for normal entrainment of behavior to light-dark (LD) cycles. Positively regulates the CLOCK-BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1. Regulates deacetylation of BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression. With TFCP2L1, promotes establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation. Binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses.

Subunit / interactions. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with RBBP4; the interaction is direct. Interacts with BMAL1. Interacts with CLOCK. Interacts with COP1. Interacts with CSNK1G2 in the cytoplasm. Interacts with EP300. Interacts with HDAC2. Interacts with IFI16. Interacts with ITGB3BP/CENPR. Interacts with MBD3L2. Interacts with MDM2. Interacts with NACC2. Interacts with p53/TP53. Interacts with PIAS1. Interacts with PIAS3. Interacts with PIAS4. Interacts with PWWP2A. Interacts with PWWP2B. Interacts with SENP1. Interacts with SENP2. Interacts with SIX3; facilitates the binding of SIX3 to the core DNA motif of SIX3 promoter. Interacts with SUMO1. Interacts with SUMO2. Interacts with TFCP2L1; which is indispensable for TFCP2L1-mediated self-renewal-promoting effect and endoderm-inhibiting action. Interacts with TFAP2C. Interacts with TPR. Interacts with UBE2I/UBC9.

Subcellular location. Nucleus Cytoplasm Nucleus. Nucleus envelope. Cytoplasm. Cytoskeleton.

Tissue specificity. Widely expressed. High expression in brain, liver, kidney, and cardiac muscle, ovaries, adrenal glands and virgin mammary glands. Higher in tumors than in adjacent normal tissue from the same individual. Up-regulated in a wide variety of cancers including breast, liver, ovarian, and colorectal cancer and its expression levels are closely correlated with tumor aggressiveness and metastasis.

Post-translational modifications. Phosphorylation by CSNK1G2/CK1 triggered by estrogen enhances corepression of estrogen receptor (ER). Acetylation is essential for its transcriptional coactivator activity. Sumoylation positively regulates its transcriptional corepressor activity but does not affect the protein stability. Sumoylated preferentially by SUMO2 or SUMO3 than SUMO1. Sumoylation is enhanced by PIAS1/3/4 and preferentially sumoylated by SUMO2 in the presence of PIAS1/3/4. Desumoylated by SENP1. Ubiquitinated by COP1, which leads to proteasomal degradation.

Disease relevance. Involved in the epigenetic regulation of ESR1 expression in breast cancer in a TFAP2C, IFI16 and HDAC4/5/6-dependent manner.

Domain organisation. Isoform Short contains a Leu-Arg-Ile-Leu-Leu motif (ER binding motif).

Similarity. Belongs to the metastasis-associated protein family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13330-1	Long	yes
Q13330-2	Short, MTA1S
Q13330-3	3

RefSeq proteins (4): NP_001190187, NP_001397990, NP_001397991, NP_004680* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000679	Znf_GATA	Domain
IPR000949	ELM2_dom	Domain
IPR001005	SANT/Myb	Domain
IPR001025	BAH_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017884	SANT_dom	Domain
IPR035170	MTA1_R1	Domain
IPR040138	MIER/MTA	Family
IPR043151	BAH_sf	Homologous_superfamily

Pfam: PF00249, PF00320, PF01426, PF01448, PF17226

UniProt features (56 total): helix 14, modified residue 9, cross-link 4, mutagenesis site 4, sequence conflict 4, domain 3, short sequence motif 3, splice variant 3, turn 3, region of interest 3, sequence variant 2, strand 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
4PBZ	X-RAY DIFFRACTION	2.15
4PBY	X-RAY DIFFRACTION	2.5
4PC0	X-RAY DIFFRACTION	2.5
6ZRD	X-RAY DIFFRACTION	2.5
6ZRC	X-RAY DIFFRACTION	2.6
6G16	X-RAY DIFFRACTION	2.8
4BKX	X-RAY DIFFRACTION	3
5FXY	X-RAY DIFFRACTION	3.2
5ICN	X-RAY DIFFRACTION	3.3
7AO8	ELECTRON MICROSCOPY	4.5
7AO9	ELECTRON MICROSCOPY	6.1
7AOA	ELECTRON MICROSCOPY	19.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13330-F1	73.29	0.42

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 (13): 386, 446, 449, 522, 564, 576, 578, 626, 639, 182, 509, 549, 626

Mutagenesis-validated functional residues (4):

Position	Phenotype
182	reduced ubiquitination. significant reduction in ubiquitination; when associated with a-626.
509	reduced sumoylation and transcriptional corepressor activity.
626	loss of acetylation and transcriptional coactivator activity. reduced ubiquitination. significant reduction in ubiquitin
711–713	significant loss of interaction with sumo1 and sumo2 and reduced transcriptional corepressor activity.

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-3232118	SUMOylation of transcription factors
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1266738	Developmental Biology
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-392499	Metabolism of proteins
R-HSA-4839726	Chromatin organization
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-6807070	PTEN Regulation
R-HSA-73854	RNA Polymerase I Promoter Clearance
R-HSA-73864	RNA Polymerase I Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 254 (showing top): GOBP_CIRCADIAN_RHYTHM, MORF_MTA1, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_BEHAVIOR, GOBP_PHOTOPERIODISM, TTTGTAG_MIR520D, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MORF_RAD21, MORF_HDAC2, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, PUJANA_CHEK2_PCC_NETWORK, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), double-strand break repair (GO:0006302), chromatin remodeling (GO:0006338), signal transduction (GO:0007165), response to ionizing radiation (GO:0010212), circadian regulation of gene expression (GO:0032922), regulation of cell fate specification (GO:0042659), entrainment of circadian clock by photoperiod (GO:0043153), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), locomotor rhythm (GO:0045475), negative regulation of gene expression, epigenetic (GO:0045814), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of protein autoubiquitination (GO:1902499), regulation of stem cell differentiation (GO:2000736), regulation of DNA-templated transcription (GO:0006355), rhythmic process (GO:0048511)

GO Molecular Function (11): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), chromatin binding (GO:0003682), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), zinc ion binding (GO:0008270), histone deacetylase binding (GO:0042826), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), microtubule (GO:0005874), NuRD complex (GO:0016581), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Regulation of endogenous retroelements	2
Chromatin modifying enzymes	1
SUMO E3 ligases SUMOylate target proteins	1
Positive epigenetic regulation of rRNA expression	1
RNA Polymerase I Promoter Clearance	1
PTEN Regulation	1
SARS-CoV Infections	1
Transcriptional regulation of brown and beige adipocyte differentiation	1
CHD3, CHD4, CHD5 subfamily	1
NuRD complex assembly	1
Differentiation of T cells	1
Intracellular signaling by second messengers	1
Gene expression (Transcription)	1
Post-translational protein modification	1
SUMOylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
cellular anatomical structure	3
negative regulation of DNA-templated transcription	2
regulation of gene expression	2
regulation of DNA-templated transcription	2
binding	2
transcription coregulator activity	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
DNA repair	1
chromatin organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to radiation	1
circadian rhythm	1
cell fate specification	1
regulation of cell fate commitment	1
photoperiodism	1
entrainment of circadian clock	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
locomotory behavior	1
circadian behavior	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of protein ubiquitination	1
protein autoubiquitination	1
regulation of protein autoubiquitination	1
regulation of cell differentiation	1
stem cell differentiation	1
regulation of RNA biosynthetic process	1
biological_process	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
positive regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

1376 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTA1	RBBP4	P31149	997
MTA1	CHD4	Q14839	997
MTA1	RBBP7	Q16576	997
MTA1	HDAC1	Q13547	996
MTA1	HDAC2	Q92769	995
MTA1	CHD3	Q12873	993
MTA1	GATAD2A	Q86YP4	993
MTA1	GATAD2B	Q8WXI9	962
MTA1	MTA2	O94776	960
MTA1	MTA3	Q9BTC8	896
MTA1	ESR1	P03372	859
MTA1	MBD2	Q9UBB5	796
MTA1	MBD3	O95983	789
MTA1	CDK2AP1	O14519	719
MTA1	PELP1	Q8IZL8	710

IntAct

260 interactions, top by confidence:

A	B	Type	Score
MTA1	HDAC1	psi-mi:“MI:0915”(physical association)	0.940
MTA1	RBBP4	psi-mi:“MI:0915”(physical association)	0.930
RBBP4	MTA1	psi-mi:“MI:0915”(physical association)	0.930
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
CHD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
CHD4	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
IKZF1	MTA1	psi-mi:“MI:0915”(physical association)	0.670
MTA1	KRT40	psi-mi:“MI:0915”(physical association)	0.670
KRT40	MTA1	psi-mi:“MI:0915”(physical association)	0.670
MTA1	IKZF1	psi-mi:“MI:0915”(physical association)	0.670
KPNA4	MTA1	psi-mi:“MI:0915”(physical association)	0.670
HDAC1	ZEB2	psi-mi:“MI:0914”(association)	0.640

BioGRID (633): MTA1 (Two-hybrid), MTA1 (Two-hybrid), MTA1 (Two-hybrid), MTA1 (Two-hybrid), MTA1 (Two-hybrid), IKZF1 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), KHDRBS2 (Two-hybrid), KRTAP10-8 (Two-hybrid), NOTCH2NL (Two-hybrid), MTA1 (Affinity Capture-Western), MTA1 (Affinity Capture-MS), MTA1 (Affinity Capture-MS), MTA1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNN3, A2AWA9, B1H2N3, B5DEN9, B5DGH9, O43242, O60941, O76031, P14685, P60228, P60229, Q05AY2, Q06364, Q07866, Q0IIL1, Q13330, Q1LUA8, Q28FE2, Q2KJ46, Q3B8M3, Q3T102, Q4QR03, Q4R6G8, Q503N9, Q5F428, Q5R7N3, Q5R8K9, Q5R8N4, Q5RAN1, Q5U2U0, Q5ZLA5, Q62599, Q641X8, Q6DH26, Q6DRI1, Q6GQA1, Q6P6Q9, Q6P7L9, Q7Z3J2, Q8K4B0

Diamond homologs: A6QL72, O94776, Q13330, Q62599, Q8K4B0, Q924K8, Q9BTC8, Q9R190, Q59E36, Q62901, Q6NRZ0, Q80TZ9, Q9P2R6, Q5REE1, Q5UAK0, Q5ZKT9, Q8N108, A5PJX4, Q0GGX2, Q3U3N0, Q3UHF3, Q4R2Z8, Q4R3R9, Q7T105, Q7Z3K6, Q8N344, Q9H0D2, Q18919, Q6PJG2, O35126, P54258, P54259, Q09228, Q5IS70

SIGNOR signaling

15 interactions.

A	Effect	B	Mechanism
MTA1	“form complex”	“MTA1/DJ1 complex”	binding
PITX3	“up-regulates activity”	MTA1	binding
MTA1	“down-regulates quantity by repression”	EPHA2	“transcriptional regulation”
MTA1	“down-regulates quantity by repression”	CDH1	“transcriptional regulation”
MTA1	“down-regulates quantity by repression”	MTA3	“transcriptional regulation”
MTA1	“up-regulates quantity by expression”	SNAI1	“transcriptional regulation”
MTA1	“up-regulates quantity by expression”	SNAI2	“transcriptional regulation”
MTA1	“up-regulates quantity by expression”	CXCL1	“transcriptional regulation”
MTA1	“form complex”	“MBD2/NuRD complex”	binding
MTA1	“form complex”	“MBD3/NuRD complex”	binding
COP1	“down-regulates quantity by destabilization”	MTA1	polyubiquitination
MTA1	“down-regulates quantity by destabilization”	COP1	binding
CSNK1G2	“up-regulates activity”	MTA1	phosphorylation
CLOCK/BMAL1	“up-regulates quantity by expression”	MTA1	“transcriptional regulation”
MTA1	“up-regulates activity”	CLOCK/BMAL1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 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
Regulation of TP53 Activity through Acetylation	10	41.1×	1e-12
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	11	37.7×	3e-13
Regulation of PTEN gene transcription	17	27.3×	1e-17
RNA Polymerase I Transcription Initiation	12	24.2×	3e-12
NuRD complex assembly	17	21.6×	4e-16
Interaction of NuRD complexes with transcription factors	17	19.4×	2e-15
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	14	19.2×	1e-12
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	14	18.5×	1e-12

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	11	62.0×	2e-15
DNA methylation-dependent constitutive heterochromatin formation	7	28.0×	8e-07
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	14.8×	2e-03
circadian regulation of gene expression	6	10.3×	2e-03
chromatin remodeling	17	9.1×	1e-09
double-strand break repair	6	9.0×	4e-03
chromatin organization	12	8.8×	2e-06
nucleosome assembly	7	7.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3815 predictions. Top by Δscore:

Variant	Effect	Δscore
14:105438663:T:A	acceptor_gain	1.0000
14:105445413:TACAG:T	acceptor_loss	1.0000
14:105445415:CAGAC:C	acceptor_loss	1.0000
14:105445508:GCAA:G	donor_gain	1.0000
14:105445511:AGTG:A	donor_loss	1.0000
14:105445512:G:GG	donor_gain	1.0000
14:105445513:T:G	donor_loss	1.0000
14:105450054:TCA:T	acceptor_loss	1.0000
14:105450055:CAG:C	acceptor_loss	1.0000
14:105450056:A:AG	acceptor_gain	1.0000
14:105450056:AG:A	acceptor_gain	1.0000
14:105450056:AGG:A	acceptor_gain	1.0000
14:105450056:AGGG:A	acceptor_gain	1.0000
14:105450057:G:GA	acceptor_gain	1.0000
14:105450057:GG:G	acceptor_gain	1.0000
14:105450057:GGG:G	acceptor_gain	1.0000
14:105450057:GGGG:G	acceptor_gain	1.0000
14:105450057:GGGGA:G	acceptor_gain	1.0000
14:105454307:GAAG:G	donor_gain	1.0000
14:105454308:AAGGT:A	donor_loss	1.0000
14:105454309:AGG:A	donor_loss	1.0000
14:105454310:GGTAG:G	donor_loss	1.0000
14:105454312:T:A	donor_loss	1.0000
14:105458370:CCGGT:C	donor_loss	1.0000
14:105458373:G:GA	donor_loss	1.0000
14:105458374:TGA:T	donor_loss	1.0000
14:105458375:GAG:G	donor_loss	1.0000
14:105460356:A:AG	acceptor_gain	1.0000
14:105460357:G:GG	acceptor_gain	1.0000
14:105460357:GCT:G	acceptor_gain	1.0000

AlphaMissense

4668 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:105420051:T:C	Y6H	1.000
14:105420054:A:T	R7W	1.000
14:105420055:G:T	R7M	1.000
14:105420056:G:C	R7S	1.000
14:105420056:G:T	R7S	1.000
14:105420060:G:A	G9R	1.000
14:105420060:G:C	G9R	1.000
14:105420061:G:A	G9E	1.000
14:105420061:G:T	G9V	1.000
14:105438678:T:A	V12D	1.000
14:105438683:T:C	F14L	1.000
14:105438684:T:C	F14S	1.000
14:105438685:T:A	F14L	1.000
14:105438685:T:G	F14L	1.000
14:105438686:G:A	E15K	1.000
14:105438705:C:A	P21Q	1.000
14:105438717:G:C	R25P	1.000
14:105438720:G:C	R26T	1.000
14:105438721:A:C	R26S	1.000
14:105438721:A:T	R26S	1.000
14:105438723:T:A	I27N	1.000
14:105438723:T:G	I27S	1.000
14:105438728:G:A	E29K	1.000
14:105438732:T:A	L30H	1.000
14:105438732:T:C	L30P	1.000
14:105438732:T:G	L30R	1.000
14:105438739:G:C	K32N	1.000
14:105438739:G:T	K32N	1.000
14:105445427:G:A	G36R	1.000
14:105445427:G:C	G36R	1.000

dbSNP variants (sampled 300 via entrez): RS1000218127 (14:105456231 G>A,C), RS1000239590 (14:105423055 C>G), RS1000374998 (14:105466282 C>A,G,T), RS1000378320 (14:105433555 C>A), RS1000435226 (14:105462249 C>T), RS1000550850 (14:105454949 A>C), RS1000589919 (14:105454709 C>T), RS1000615286 (14:105422138 G>A,C,T), RS1000681975 (14:105423407 G>T), RS1000700841 (14:105465190 A>C,G), RS1000789693 (14:105438081 T>A,C), RS1000840302 (14:105437857 T>A,G), RS1000884814 (14:105469322 C>A,T), RS1000889995 (14:105427895 G>A), RS1001039672 (14:105421933 A>T)

Disease associations

OMIM: gene MIM:603526 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006979_1016	Heel bone mineral density	4.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724629 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases methylation	4
Valproic Acid	affects expression, decreases expression, increases methylation	4
bisphenol A	affects binding, decreases reaction, decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	3
Arsenic	affects methylation, decreases expression, increases abundance, increases expression	3
Arsenic Trioxide	decreases expression	2
Benzo(a)pyrene	increases mutagenesis, increases methylation	2
Cadmium	decreases expression	2
Estradiol	affects binding, decreases reaction, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Tretinoin	decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	increases expression, increases abundance, affects cotreatment	1
deoxynivalenol	increases expression	1
lead acetate	increases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, increases expression	1
cadmium acetate	increases expression	1
bathocuproine sulfonate	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
coumarin	decreases phosphorylation	1
andrographolide	decreases expression	1
nivalenol	increases expression	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697625	Binding	Inhibition of MTA1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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