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MGP003800

UniProt Annotations

Entry Information

Gene Name	metastasis associated 1
Protein Entry	MTA1_HUMAN
UniProt ID	Q13330
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=Long; IsoId=Q13330-1; Sequence=Displayed; Name=Short; Synonyms=MTA1S; IsoId=Q13330-2; Sequence=VSP_001601, VSP_001602; Name=3; IsoId=Q13330-3; Sequence=VSP_042207;
Developmental Stage	Highly expressed in metastatic cells.
Domain	Isoform Short contains a Leu-Arg-Ile-Leu-Leu motif (ER binding motif).
Function	Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator. As a part of the histone-deacetylase multiprotein complex (NuRD), 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, PAX5 and SUMO2, independent of the NuRD complex. Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3. Plays a role in the inflammatory responses, both as a target and as a component of the NF-kappa-B signaling and regulates a subset of proinflammatory cytokines such as IL1B, MIP2, and TNF. 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 an important role in tumorigenesis, tumor invasion, and metastasis. Involved in the epigenetic regulation of ESR1 expression in breast cancer in a TFAP2C, IFI16 and HDAC4/5/6-dependent manner. 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-ARNTL/BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1. Regulates deacetylation of ARNTL/BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1- mediated transcription repression. Isoform Short binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses. {ECO:0000269\|PubMed:16617102, ECO:0000269\|PubMed:17671180, ECO:0000269\|PubMed:17922032, ECO:0000269\|PubMed:19837670, ECO:0000269\|PubMed:21965678, ECO:0000269\|PubMed:24413532}.
Interaction	P03372:ESR1; NbExp=4; IntAct=EBI-714236, EBI-78473; Q13547:HDAC1; NbExp=4; IntAct=EBI-714236, EBI-301834; Q92769:HDAC2; NbExp=4; IntAct=EBI-714236, EBI-301821; Q16665:HIF1A; NbExp=6; IntAct=EBI-714236, EBI-447269;
Ptm	Acetylation is essential for its transcriptional coactivator activity. {ECO:0000269\|PubMed:16617102, ECO:0000269\|PubMed:17671180, ECO:0000269\|PubMed:19805145}.
Ptm	Phosphorylation by CSNK1G2/CK1 triggered by estrogen enhances corepression of estrogen receptor (ER). {ECO:0000269\|PubMed:15077195, ECO:0000269\|PubMed:16964243, ECO:0000269\|PubMed:18669648, ECO:0000269\|PubMed:18691976, ECO:0000269\|PubMed:19690332, ECO:0000269\|PubMed:20068231, ECO:0000269\|PubMed:21406692}.
Ptm	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. {ECO:0000269\|PubMed:21965678}.
Ptm	Ubiquitinated by RFWD2, which leads to proteasomal degradation. {ECO:0000269\|PubMed:19805145}.
Similarity	Contains 1 BAH domain. {ECO:0000255\|PROSITE- ProRule:PRU00370}.
Similarity	Contains 1 ELM2 domain. {ECO:0000255\|PROSITE- ProRule:PRU00512}.
Similarity	Contains 1 GATA-type zinc finger. {ECO:0000305}.
Similarity	Contains 1 SANT domain. {ECO:0000255\|PROSITE- ProRule:PRU00624}.
Subcellular Location	Isoform Long: Nucleus. Nucleus envelope. Cytoplasm. Cytoplasm, cytoskeleton. Note=Associated with microtubules. Localization at the nuclear envelope is TPR- dependent.
Subcellular Location	Isoform Short: Cytoplasm.
Subunit	Component of the nucleosome-remodeling and histone- deacetylase multiprotein complex (NuRD). Interacts with HDAC1 and ITGB3BP/CENPR. Binds to CSNK1G2 in the cytoplasm. Interacts with NACC2. Interacts with ARNTL/BMAL1 and CLOCK. Interacts with EP300, TFAP2C, IFI16, TPR, HDAC2, UBE2I/UBC9, PIAS1, PIAS3, PIAS4, p53/TP53, MDM2, RFWD2, SUMO1, SUMO2, SENP1 and SENP2. Interacts with SIX3; facilitates the binding of SIX3 to the core DNA motif of SIX3 promoter (By similarity). {ECO:0000250\|UniProtKB:Q8K4B0, ECO:0000269\|PubMed:15077195, ECO:0000269\|PubMed:15254226, ECO:0000269\|PubMed:16617102, ECO:0000269\|PubMed:17671180, ECO:0000269\|PubMed:19805145, ECO:0000269\|PubMed:19837670, ECO:0000269\|PubMed:20682799, ECO:0000269\|PubMed:21965678, ECO:0000269\|PubMed:22926524, ECO:0000269\|PubMed:24413532, ECO:0000269\|PubMed:24970816, ECO:0000269\|PubMed:9885572}.
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. {ECO:0000269\|PubMed:16617102, ECO:0000269\|PubMed:24970816}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MTA1ID41443ch14q32.html";