MTA1_RAT
ID MTA1_RAT Reviewed; 703 AA.
AC Q62599; Q9Z0N8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 169.
DE RecName: Full=Metastasis-associated protein MTA1;
GN Name=Mta1; Synonyms=Zg29;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Fischer 344; TISSUE=Mammary gland;
RX PubMed=8083195; DOI=10.1016/s0021-9258(17)31603-4;
RA Toh Y., Pencil S.D., Nicolson G.L.;
RT "A novel candidate metastasis-associated gene, mta1, differentially
RT expressed in highly metastatic mammary adenocarcinoma cell lines. cDNA
RT cloning, expression, and protein analyses.";
RL J. Biol. Chem. 269:22958-22963(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Fischer 344; TISSUE=Mammary gland;
RX PubMed=7607577; DOI=10.1016/0378-1119(94)00410-t;
RA Toh Y., Pencil S.D., Nicolson G.L.;
RT "Analysis of the complete sequence of the novel metastasis-associated
RT candidate gene, mta1, differentially expressed in mammary adenocarcinoma
RT and breast cancer cell lines.";
RL Gene 159:97-104(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORMS 1
RP AND 2), TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Wistar; TISSUE=Pancreas;
RX PubMed=10393810; DOI=10.1242/jcs.112.15.2539;
RA Kleene R., Zdzieblo J., Wege K., Kern H.-F.;
RT "A novel zymogen granule protein (ZG29p) and the nuclear protein MTA1p are
RT differentially expressed by alternative transcription initiation in
RT pancreatic acinar cells of the rat.";
RL J. Cell Sci. 112:2539-2548(1999).
RN [4]
RP PUTATIVE FUNCTION, AND INTERACTION WITH AMYLASE.
RX PubMed=10933808; DOI=10.1021/bi000876i;
RA Kleene R., Classen B., Zdzieblo J., Schrader M.;
RT "SH3 binding sites of ZG29p mediate an interaction with amylase and are
RT involved in condensation-sorting in the exocrine rat pancreas.";
RL Biochemistry 39:9893-9900(2000).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-522 AND SER-576, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Transcriptional coregulator which can act as both a
CC transcriptional corepressor and coactivator. As a part of the histone-
CC deacetylase multiprotein complex (NuRD), regulates transcription of its
CC targets by modifying the acetylation status of the target chromatin and
CC cofactor accessibility to the target DNA. In conjunction with other
CC components of NuRD, acts as a transcriptional corepressor of BRCA1,
CC ESR1, TFF1 and CDKN1A. Acts as a transcriptional coactivator of BCAS3,
CC PAX5 and SUMO2, independent of the NuRD complex. Stimulates the
CC expression of WNT1 by inhibiting the expression of its transcriptional
CC corepressor SIX3. Regulates p53-dependent and -independent DNA repair
CC processes following genotoxic stress. Regulates the stability and
CC function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2
CC thereby regulating the p53-dependent DNA repair. Plays an important
CC role in tumorigenesis, tumor invasion, and metastasis. Plays a role in
CC the regulation of the circadian clock and is essential for the
CC generation and maintenance of circadian rhythms under constant light
CC and for normal entrainment of behavior to light-dark (LD) cycles.
CC Positively regulates the CLOCK-ARNTL/BMAL1 heterodimer mediated
CC transcriptional activation of its own transcription and the
CC transcription of CRY1. Regulates deacetylation of ARNTL/BMAL1 by
CC regulating SIRT1 expression, resulting in derepressing CRY1-mediated
CC transcription repression (By similarity). Isoform 2 may be involved in
CC the sorting of amylase during zymogen granule formation in the
CC pancreas. With Tfcp2l1, promotes establishment and maintenance of
CC pluripotency in embryonic stem cells (ESCs) and inhibits endoderm
CC differentiation (By similarity). {ECO:0000250|UniProtKB:Q13330,
CC ECO:0000250|UniProtKB:Q8K4B0, ECO:0000269|PubMed:10933808}.
CC -!- SUBUNIT: Isoform 1 is a component of the nucleosome-remodeling and
CC histone-deacetylase multiprotein complex (NuRD). Interacts with HDAC1
CC and ITGB3BP/CENPR. Binds to CSNK1G2 in the cytoplasm. Isoform 2
CC interacts with amylase. Interacts with NACC2. Interacts with
CC ARNTL/BMAL1 and CLOCK. Interacts with EP300, TFAP2C, IFI16, TPR, HDAC2,
CC UBE2I/UBC9, PIAS1, PIAS3, PIAS4, p53/TP53, MDM2, COP1, SUMO1, SUMO2,
CC SENP1 and SENP2. Interacts with SIX3; facilitates the binding of SIX3
CC to the core DNA motif of SIX3 promoter (By similarity). Interacts with
CC PWWP2A and PWWP2B (By similarity). {ECO:0000250|UniProtKB:Q13330,
CC ECO:0000250|UniProtKB:Q8K4B0}.
CC -!- INTERACTION:
CC Q62599; Q9ET75: Six3; NbExp=2; IntAct=EBI-349237, EBI-15649593;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:10393810}. Nucleus envelope {ECO:0000255|PROSITE-
CC ProRule:PRU00512, ECO:0000255|PROSITE-ProRule:PRU00624}. Cytoplasm
CC {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Note=Associated
CC with microtubules. Localization at the nuclear envelope is TPR-
CC dependent (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Rough endoplasmic reticulum
CC {ECO:0000269|PubMed:10393810}. Golgi apparatus
CC {ECO:0000269|PubMed:10393810}. Zymogen granule
CC {ECO:0000269|PubMed:10393810}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=MTA1, MTA1p;
CC IsoId=Q62599-1; Sequence=Displayed;
CC Name=2; Synonyms=ZG29, ZG29p;
CC IsoId=Q62599-2; Sequence=VSP_019712, VSP_019713;
CC -!- TISSUE SPECIFICITY: Isoform 1 abundant in testis and expressed at low
CC levels in brain, heart, lung, liver, and kidney. Isoform 2 abundant in
CC adrenal gland, brain, colon, heart, liver, lung, muscle, prostate,
CC stomach, testis, and thymus and expressed at low levels in duodenum,
CC kidney, pancreas, parotid, and spleen. {ECO:0000269|PubMed:10393810}.
CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: Highly expressed in metastatic cells.
CC -!- INDUCTION: [Isoform 1]: Induced by dexamethasone and, in pancreas, by
CC treatment with the proteinase inhibitor FOY-305 which binds to
CC activated trypsin and induces release of cholecystokinin.
CC {ECO:0000269|PubMed:10393810}.
CC -!- PTM: Phosphorylation by CSNK1G2/CK1 triggered by estrogen enhances
CC corepression of estrogen receptor (ER). {ECO:0000250}.
CC -!- PTM: Acetylation is essential for its transcriptional coactivator
CC activity. {ECO:0000250}.
CC -!- PTM: Sumoylation positively regulates its transcriptional corepressor
CC activity but does not affect the protein stability. Sumoylated
CC preferentially by SUMO2 or SUMO3 than SUMO1. Sumoylation is enhanced by
CC PIAS1/3/4 and preferentially sumoylated by SUMO2 in the presence of
CC PIAS1/3/4. Desumoylated by SENP1 (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by COP1, which leads to proteasomal degradation.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing and
CC alternative initiation at Met-465 of isoform 1. {ECO:0000305}.
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DR EMBL; U02522; AAA82722.1; -; mRNA.
DR EMBL; AJ132046; CAB38718.1; -; mRNA.
DR PIR; A54766; A54766.
DR RefSeq; NP_072110.1; NM_022588.1. [Q62599-1]
DR AlphaFoldDB; Q62599; -.
DR SMR; Q62599; -.
DR BioGRID; 249104; 1.
DR DIP; DIP-33254N; -.
DR IntAct; Q62599; 3.
DR MINT; Q62599; -.
DR STRING; 10116.ENSRNOP00000051141; -.
DR iPTMnet; Q62599; -.
DR PhosphoSitePlus; Q62599; -.
DR jPOST; Q62599; -.
DR PaxDb; Q62599; -.
DR PRIDE; Q62599; -.
DR GeneID; 64520; -.
DR KEGG; rno:64520; -.
DR UCSC; RGD:621018; rat. [Q62599-1]
DR CTD; 9112; -.
DR RGD; 621018; Mta1.
DR eggNOG; KOG3554; Eukaryota.
DR InParanoid; Q62599; -.
DR OrthoDB; 802091at2759; -.
DR PhylomeDB; Q62599; -.
DR Reactome; R-RNO-3214815; HDACs deacetylate histones.
DR Reactome; R-RNO-3232118; SUMOylation of transcription factors.
DR Reactome; R-RNO-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-RNO-8943724; Regulation of PTEN gene transcription.
DR PRO; PR:Q62599; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; Q62599; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISS:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016581; C:NuRD complex; ISO:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0042588; C:zymogen granule; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; IEA:InterPro.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0006338; P:chromatin remodeling; ISO:RGD.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0016575; P:histone deacetylation; ISO:RGD.
DR GO; GO:0045475; P:locomotor rhythm; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:1902499; P:positive regulation of protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; ISS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0033363; P:secretory granule organization; IDA:UniProtKB.
DR CDD; cd00202; ZnF_GATA; 1.
DR Gene3D; 2.30.30.490; -; 1.
DR InterPro; IPR001025; BAH_dom.
DR InterPro; IPR043151; BAH_sf.
DR InterPro; IPR000949; ELM2_dom.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR040138; MIER/MTA.
DR InterPro; IPR035170; MTA1_R1.
DR InterPro; IPR017930; Myb_dom.
DR InterPro; IPR001005; SANT/Myb.
DR InterPro; IPR017884; SANT_dom.
DR InterPro; IPR000679; Znf_GATA.
DR PANTHER; PTHR10865; PTHR10865; 1.
DR Pfam; PF01426; BAH; 1.
DR Pfam; PF01448; ELM2; 1.
DR Pfam; PF00320; GATA; 1.
DR Pfam; PF17226; MTA_R1; 2.
DR Pfam; PF00249; Myb_DNA-binding; 1.
DR SMART; SM00439; BAH; 1.
DR SMART; SM01189; ELM2; 1.
DR SMART; SM00717; SANT; 1.
DR SMART; SM00401; ZnF_GATA; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS51038; BAH; 1.
DR PROSITE; PS51156; ELM2; 1.
DR PROSITE; PS51293; SANT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative initiation; Alternative splicing;
KW Biological rhythms; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton;
KW DNA-binding; Endoplasmic reticulum; Golgi apparatus; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..703
FT /note="Metastasis-associated protein MTA1"
FT /id="PRO_0000083495"
FT DOMAIN 1..164
FT /note="BAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00370"
FT DOMAIN 165..276
FT /note="ELM2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00512"
FT DOMAIN 283..335
FT /note="SANT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00624"
FT ZN_FING 393..420
FT /note="GATA-type; atypical"
FT REGION 437..460
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 542..583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 661..703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 545..552
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 684..693
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 699..703
FT /note="SUMO interaction motif 1 (SIM); crucial for
FT efficient sumoylation"
FT /evidence="ECO:0000250"
FT COMPBIAS 554..583
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 564
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT MOD_RES 576
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 578
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT MOD_RES 614
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT CROSSLNK 182
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT CROSSLNK 509
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2 and SUMO3)"
FT /evidence="ECO:0000250"
FT CROSSLNK 549
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT CROSSLNK 614
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q13330"
FT VAR_SEQ 1..464
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10393810"
FT /id="VSP_019712"
FT VAR_SEQ 593
FT /note="G -> GNMKKRLLMPSRG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10393810"
FT /id="VSP_019713"
SQ SEQUENCE 703 AA; 79412 MW; F05D8D287C45F13A CRC64;
MAANMYRVGD YVYFENSSSN PYLIRRIEEL NKTANGNVEA KVVCFYRRRD ISSSLIALAD
KHATLSVCYR AGPGADTGEE GEVEEEVENP EMVDLPEKLK HQLRHRELFL SRQLESLPAT
HIRGKCSVTL LNETESLKSY LEREDFFFYS LVYDPQQKTL LADKGEIRVG NRYQADITDL
LKDGEEDGRD QSKLETKVWE AHNPLVDKQI DQFLVVARSV GTFARALDCS SSVRQPSLHM
SAAAASRDIT LFHAMDTLHK NIYDISKAIS ALVPQGGPVL CRDEMEEWSA SEANLFEEAL
EKYGKDFTDI QQDFLPWKSL TSIIEYYYMW KTTDRYVQQK RLKAAEAESK LKQVYIPNYN
KPNPNQISVN SVKASVVNGT GTPGQSPGAG RACESCYTTQ SYQWYSWGPP NMQCRLCASC
WTYWKKYGGL KMPTRLDGER PGPNRNNMSP HGIPARSSGS PKFAMKTRQA FYLHTTKLTR
IARRLCREIL RPWHAARHPY MPINSAAIKA ECTARLPEAS QSPLVLKQVV RKPLEAVLRY
LETHPRPPKP DPVKSSSSVL SSLTPAKSAP VINNGSPTIL GKRSYEQHNG VDGLANHGQT
RHMGPSRNLL LNGKSYPTKV RLIRGGSLPP VKRRRMNWID APDDVFYMAT EETRKIRKLL
SSSETKRAAR RPYKPIALRQ SQALPLRPPP PAPVNDEPIV IED
