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Protein

Metastasis-associated protein MTA1

Gene

Mta1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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 2 may be involved in the sorting of amylase during zymogen granule formation in the pancreas.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri393 – 42028GATA-type; atypicalAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-3232118. SUMOylation of transcription factors.
R-RNO-73762. RNA Polymerase I Transcription Initiation.

Names & Taxonomyi

Protein namesi
Recommended name:
Metastasis-associated protein MTA1
Gene namesi
Name:Mta1
Synonyms:Zg29
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621018. Mta1.

Subcellular locationi

Isoform 1 :

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • microtubule Source: UniProtKB
  • nuclear envelope Source: UniProtKB
  • nucleus Source: UniProtKB
  • rough endoplasmic reticulum Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endoplasmic reticulum, Golgi apparatus, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 703703Metastasis-associated protein MTA1PRO_0000083495Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki182 – 182Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei386 – 3861PhosphoserineBy similarity
Modified residuei449 – 4491PhosphoserineBy similarity
Cross-linki509 – 509Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2 and SUMO3)By similarity
Modified residuei522 – 5221PhosphoserineCombined sources
Modified residuei564 – 5641PhosphothreonineBy similarity
Modified residuei576 – 5761PhosphoserineCombined sources
Modified residuei578 – 5781PhosphothreonineBy similarity
Modified residuei614 – 6141N6-acetyllysine; alternateBy similarity
Cross-linki614 – 614Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternateBy similarity
Modified residuei627 – 6271PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation by CSNK1G2/CK1 triggered by estrogen enhances corepression of estrogen receptor (ER).By similarity
Acetylation is essential for its transcriptional coactivator activity.By similarity
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 (By similarity).By similarity
Ubiquitinated by RFWD2, which leads to proteasomal degradation.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ62599.
PRIDEiQ62599.

PTM databases

iPTMnetiQ62599.
PhosphoSiteiQ62599.

Expressioni

Tissue specificityi

Isoform 1 abundant in testis and expressed at low levels in brain, heart, lung, liver, and kidney. Isoform 2 abundant in adrenal gland, brain, colon, heart, liver, lung, muscle, prostate, stomach, testis, and thymus and expressed at low levels in duodenum, kidney, pancreas, parotid, and spleen.1 Publication

Developmental stagei

Isoform 1 is highly expressed in metastatic cells.

Inductioni

Isoform 1 is induced by dexamethasone and, in pancreas, by treatment with the proteinase inhibitor FOY-305 which binds to activated trypsin and induces release of cholecystokinin.1 Publication

Gene expression databases

GenevisibleiQ62599. RN.

Interactioni

Subunit structurei

Isoform 1 is a component of the nucleosome-remodeling and histone-deacetylase multiprotein complex (NuRD). Interacts with HDAC1 and ITGB3BP/CENPR. Binds to CSNK1G2 in the cytoplasm (By similarity). Isoform 2 interacts with amylase. 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).By similarity

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi249104. 1 interaction.
DIPiDIP-33254N.
IntActiQ62599. 2 interactions.
STRINGi10116.ENSRNOP00000051141.

Structurei

3D structure databases

ProteinModelPortaliQ62599.
SMRiQ62599. Positions 285-341.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 164164BAHPROSITE-ProRule annotationAdd
BLAST
Domaini165 – 276112ELM2PROSITE-ProRule annotationAdd
BLAST
Domaini283 – 33553SANTPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi545 – 5528SH3-bindingSequence analysis
Motifi684 – 69310SH3-bindingSequence analysis
Motifi699 – 7035SUMO interaction motif 1 (SIM); crucial for efficient sumoylationBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi688 – 6936Poly-Pro

Sequence similaritiesi

Contains 1 BAH domain.PROSITE-ProRule annotation
Contains 1 ELM2 domain.PROSITE-ProRule annotation
Contains 1 GATA-type zinc finger.Curated
Contains 1 SANT domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri393 – 42028GATA-type; atypicalAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3554. Eukaryota.
ENOG410XSAJ. LUCA.
HOGENOMiHOG000045387.
HOVERGENiHBG002598.
InParanoidiQ62599.
KOiK11660.
PhylomeDBiQ62599.

Family and domain databases

InterProiIPR001025. BAH_dom.
IPR000949. ELM2_dom.
IPR009057. Homeodomain-like.
IPR001005. SANT/Myb.
IPR017884. SANT_dom.
IPR000679. Znf_GATA.
[Graphical view]
PfamiPF01426. BAH. 1 hit.
PF01448. ELM2. 1 hit.
PF00320. GATA. 1 hit.
PF00249. Myb_DNA-binding. 1 hit.
[Graphical view]
SMARTiSM00439. BAH. 1 hit.
SM01189. ELM2. 1 hit.
SM00717. SANT. 1 hit.
SM00401. ZnF_GATA. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS51038. BAH. 1 hit.
PS51156. ELM2. 1 hit.
PS51293. SANT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q62599-1) [UniParc]FASTAAdd to basket

Also known as: MTA1, MTA1p

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAANMYRVGD YVYFENSSSN PYLIRRIEEL NKTANGNVEA KVVCFYRRRD
60 70 80 90 100
ISSSLIALAD KHATLSVCYR AGPGADTGEE GEVEEEVENP EMVDLPEKLK
110 120 130 140 150
HQLRHRELFL SRQLESLPAT HIRGKCSVTL LNETESLKSY LEREDFFFYS
160 170 180 190 200
LVYDPQQKTL LADKGEIRVG NRYQADITDL LKDGEEDGRD QSKLETKVWE
210 220 230 240 250
AHNPLVDKQI DQFLVVARSV GTFARALDCS SSVRQPSLHM SAAAASRDIT
260 270 280 290 300
LFHAMDTLHK NIYDISKAIS ALVPQGGPVL CRDEMEEWSA SEANLFEEAL
310 320 330 340 350
EKYGKDFTDI QQDFLPWKSL TSIIEYYYMW KTTDRYVQQK RLKAAEAESK
360 370 380 390 400
LKQVYIPNYN KPNPNQISVN SVKASVVNGT GTPGQSPGAG RACESCYTTQ
410 420 430 440 450
SYQWYSWGPP NMQCRLCASC WTYWKKYGGL KMPTRLDGER PGPNRNNMSP
460 470 480 490 500
HGIPARSSGS PKFAMKTRQA FYLHTTKLTR IARRLCREIL RPWHAARHPY
510 520 530 540 550
MPINSAAIKA ECTARLPEAS QSPLVLKQVV RKPLEAVLRY LETHPRPPKP
560 570 580 590 600
DPVKSSSSVL SSLTPAKSAP VINNGSPTIL GKRSYEQHNG VDGLANHGQT
610 620 630 640 650
RHMGPSRNLL LNGKSYPTKV RLIRGGSLPP VKRRRMNWID APDDVFYMAT
660 670 680 690 700
EETRKIRKLL SSSETKRAAR RPYKPIALRQ SQALPLRPPP PAPVNDEPIV

IED
Length:703
Mass (Da):79,412
Last modified:November 1, 1996 - v1
Checksum:iF05D8D287C45F13A
GO
Isoform 2 (identifier: Q62599-2) [UniParc]FASTAAdd to basket

Also known as: ZG29, ZG29p

The sequence of this isoform differs from the canonical sequence as follows:
     1-464: Missing.
     593-593: G → GNMKKRLLMPSRG

Note: Produced by alternative splicing and alternative initiation at Met-465 of isoform 1.
Show »
Length:251
Mass (Da):28,309
Checksum:iB15F54E8BC71CF61
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 464464Missing in isoform 2. 1 PublicationVSP_019712Add
BLAST
Alternative sequencei593 – 5931G → GNMKKRLLMPSRG in isoform 2. 1 PublicationVSP_019713

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02522 mRNA. Translation: AAA82722.1.
AJ132046 mRNA. Translation: CAB38718.1.
PIRiA54766.
RefSeqiNP_072110.1. NM_022588.1. [Q62599-1]
UniGeneiRn.5840.

Genome annotation databases

GeneIDi64520.
KEGGirno:64520.
UCSCiRGD:621018. rat. [Q62599-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02522 mRNA. Translation: AAA82722.1.
AJ132046 mRNA. Translation: CAB38718.1.
PIRiA54766.
RefSeqiNP_072110.1. NM_022588.1. [Q62599-1]
UniGeneiRn.5840.

3D structure databases

ProteinModelPortaliQ62599.
SMRiQ62599. Positions 285-341.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249104. 1 interaction.
DIPiDIP-33254N.
IntActiQ62599. 2 interactions.
STRINGi10116.ENSRNOP00000051141.

PTM databases

iPTMnetiQ62599.
PhosphoSiteiQ62599.

Proteomic databases

PaxDbiQ62599.
PRIDEiQ62599.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi64520.
KEGGirno:64520.
UCSCiRGD:621018. rat. [Q62599-1]

Organism-specific databases

CTDi9112.
RGDi621018. Mta1.

Phylogenomic databases

eggNOGiKOG3554. Eukaryota.
ENOG410XSAJ. LUCA.
HOGENOMiHOG000045387.
HOVERGENiHBG002598.
InParanoidiQ62599.
KOiK11660.
PhylomeDBiQ62599.

Enzyme and pathway databases

ReactomeiR-RNO-3232118. SUMOylation of transcription factors.
R-RNO-73762. RNA Polymerase I Transcription Initiation.

Miscellaneous databases

NextBioi613326.
PROiQ62599.

Gene expression databases

GenevisibleiQ62599. RN.

Family and domain databases

InterProiIPR001025. BAH_dom.
IPR000949. ELM2_dom.
IPR009057. Homeodomain-like.
IPR001005. SANT/Myb.
IPR017884. SANT_dom.
IPR000679. Znf_GATA.
[Graphical view]
PfamiPF01426. BAH. 1 hit.
PF01448. ELM2. 1 hit.
PF00320. GATA. 1 hit.
PF00249. Myb_DNA-binding. 1 hit.
[Graphical view]
SMARTiSM00439. BAH. 1 hit.
SM01189. ELM2. 1 hit.
SM00717. SANT. 1 hit.
SM00401. ZnF_GATA. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS51038. BAH. 1 hit.
PS51156. ELM2. 1 hit.
PS51293. SANT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA cloning, expression, and protein analyses."
    Toh Y., Pencil S.D., Nicolson G.L.
    J. Biol. Chem. 269:22958-22963(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: Fischer 344.
    Tissue: Mammary gland.
  2. "Analysis of the complete sequence of the novel metastasis-associated candidate gene, mta1, differentially expressed in mammary adenocarcinoma and breast cancer cell lines."
    Toh Y., Pencil S.D., Nicolson G.L.
    Gene 159:97-104(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: Fischer 344.
    Tissue: Mammary gland.
  3. "A novel zymogen granule protein (ZG29p) and the nuclear protein MTA1p are differentially expressed by alternative transcription initiation in pancreatic acinar cells of the rat."
    Kleene R., Zdzieblo J., Wege K., Kern H.-F.
    J. Cell Sci. 112:2539-2548(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
    Strain: Wistar.
    Tissue: Pancreas.
  4. "SH3 binding sites of ZG29p mediate an interaction with amylase and are involved in condensation-sorting in the exocrine rat pancreas."
    Kleene R., Classen B., Zdzieblo J., Schrader M.
    Biochemistry 39:9893-9900(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: PUTATIVE FUNCTION, INTERACTION WITH AMYLASE.
  5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-522 AND SER-576, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiMTA1_RAT
AccessioniPrimary (citable) accession number: Q62599
Secondary accession number(s): Q9Z0N8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: May 11, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.