ID MT1A_HUMAN Reviewed; 61 AA.
AC P04731; Q86YX5;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 2.
DT 27-MAR-2024, entry version 190.
DE RecName: Full=Metallothionein-1A;
DE Short=MT-1A;
DE AltName: Full=Metallothionein-IA;
DE Short=MT-IA;
GN Name=MT1A; Synonyms=MT1S;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-27.
RX PubMed=6327055; DOI=10.1016/0092-8674(84)90322-2;
RA Richards R.I., Heguy A., Karin M.;
RT "Structural and functional analysis of the human metallothionein-IA gene:
RT differential induction by metal ions and glucocorticoids.";
RL Cell 37:263-272(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Wang J., Zheng L., Yu L.;
RT "Cloning of a novel member of the MT gene family - MT1S.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-27.
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Metallothioneins have a high content of cysteine residues
CC that bind various heavy metals; these proteins are transcriptionally
CC regulated by both heavy metals and glucocorticoids.
CC -!- SUBUNIT: Monomer.
CC -!- INTERACTION:
CC P04731; Q13585: GPR50; NbExp=3; IntAct=EBI-8045030, EBI-8550965;
CC P04731; P04637: TP53; NbExp=3; IntAct=EBI-8045030, EBI-366083;
CC -!- DOMAIN: Class I metallothioneins contain 2 metal-binding domains: four
CC divalent ions are chelated within cluster A of the alpha domain and are
CC coordinated via cysteinyl thiolate bridges to 11 cysteine ligands.
CC Cluster B, the corresponding region within the beta domain, can ligate
CC three divalent ions to 9 cysteines.
CC -!- SIMILARITY: Belongs to the metallothionein superfamily. Type 1 family.
CC {ECO:0000305}.
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DR EMBL; K01383; AAA59586.1; -; Genomic_DNA.
DR EMBL; AY028617; AAK26162.1; -; mRNA.
DR EMBL; AF348995; AAO32955.1; -; mRNA.
DR EMBL; AC026461; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC029475; AAH29475.1; -; mRNA.
DR CCDS; CCDS32454.1; -.
DR PIR; A24502; SMHU1A.
DR RefSeq; NP_005937.2; NM_005946.2.
DR AlphaFoldDB; P04731; -.
DR SMR; P04731; -.
DR BioGRID; 110595; 2.
DR IntAct; P04731; 4.
DR MINT; P04731; -.
DR STRING; 9606.ENSP00000290705; -.
DR DrugBank; DB00958; Carboplatin.
DR DrugBank; DB00515; Cisplatin.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB00435; Nitric Oxide.
DR DrugBank; DB00526; Oxaliplatin.
DR DrugBank; DB12965; Silver.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR iPTMnet; P04731; -.
DR PhosphoSitePlus; P04731; -.
DR BioMuta; MT1A; -.
DR jPOST; P04731; -.
DR MassIVE; P04731; -.
DR MaxQB; P04731; -.
DR PaxDb; 9606-ENSP00000478425; -.
DR PeptideAtlas; P04731; -.
DR ProteomicsDB; 51737; -.
DR Antibodypedia; 58438; 73 antibodies from 16 providers.
DR DNASU; 4489; -.
DR Ensembl; ENST00000290705.12; ENSP00000290705.8; ENSG00000205362.11.
DR GeneID; 4489; -.
DR KEGG; hsa:4489; -.
DR MANE-Select; ENST00000290705.12; ENSP00000290705.8; NM_005946.3; NP_005937.2.
DR UCSC; uc002ejq.5; human.
DR AGR; HGNC:7393; -.
DR CTD; 4489; -.
DR DisGeNET; 4489; -.
DR GeneCards; MT1A; -.
DR HGNC; HGNC:7393; MT1A.
DR HPA; ENSG00000205362; Tissue enhanced (adipose tissue, liver).
DR MIM; 156350; gene.
DR neXtProt; NX_P04731; -.
DR OpenTargets; ENSG00000205362; -.
DR PharmGKB; PA31198; -.
DR VEuPathDB; HostDB:ENSG00000205362; -.
DR eggNOG; KOG4738; Eukaryota.
DR GeneTree; ENSGT00950000182967; -.
DR HOGENOM; CLU_171204_2_0_1; -.
DR InParanoid; P04731; -.
DR OMA; CKGACSC; -.
DR TreeFam; TF336054; -.
DR PathwayCommons; P04731; -.
DR Reactome; R-HSA-5661231; Metallothioneins bind metals.
DR SignaLink; P04731; -.
DR BioGRID-ORCS; 4489; 49 hits in 1059 CRISPR screens.
DR ChiTaRS; MT1A; human.
DR GeneWiki; Metallothionein_1A; -.
DR GenomeRNAi; 4489; -.
DR Pharos; P04731; Tbio.
DR PRO; PR:P04731; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P04731; Protein.
DR Bgee; ENSG00000205362; Expressed in layer of synovial tissue and 105 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0071276; P:cellular response to cadmium ion; IEP:UniProtKB.
DR GO; GO:0071280; P:cellular response to copper ion; IBA:GO_Central.
DR GO; GO:0071294; P:cellular response to zinc ion; IEP:UniProtKB.
DR GO; GO:0010273; P:detoxification of copper ion; IBA:GO_Central.
DR GO; GO:0006882; P:intracellular zinc ion homeostasis; IBA:GO_Central.
DR GO; GO:0045926; P:negative regulation of growth; ISS:UniProtKB.
DR Gene3D; 4.10.10.10; Metallothionein Isoform II; 1.
DR InterPro; IPR017854; Metalthion_dom_sf.
DR InterPro; IPR023587; Metalthion_dom_sf_vert.
DR InterPro; IPR000006; Metalthion_vert.
DR InterPro; IPR018064; Metalthion_vert_metal_BS.
DR PANTHER; PTHR23299; METALLOTHIONEIN; 1.
DR PANTHER; PTHR23299:SF49; METALLOTHIONEIN-1A; 1.
DR Pfam; PF00131; Metallothio; 1.
DR PRINTS; PR00860; MTVERTEBRATE.
DR SUPFAM; SSF57868; Metallothionein; 1.
DR PROSITE; PS00203; METALLOTHIONEIN_VRT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cadmium; Copper; Metal-binding; Metal-thiolate cluster;
KW Phosphoprotein; Reference proteome; Zinc.
FT CHAIN 1..61
FT /note="Metallothionein-1A"
FT /id="PRO_0000197234"
FT REGION 1..29
FT /note="Beta"
FT REGION 30..61
FT /note="Alpha"
FT BINDING 5
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 7
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 7
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 13
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 15
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 15
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="3"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 19
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="3"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 21
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 24
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 24
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="3"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 26
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 29
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="3"
FT /ligand_note="in cluster B"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 33
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="4"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 34
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="4"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 34
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="5"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 36
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="5"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 37
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="5"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 37
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="6"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 41
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="6"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 44
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="4"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 44
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="6"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 48
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="4"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 50
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="5"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 50
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="7"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 57
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="7"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 59
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="7"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 60
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="6"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT BINDING 60
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="7"
FT /ligand_note="in cluster A"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P11957"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02795"
FT VARIANT 27
FT /note="T -> N (in dbSNP:rs11640851)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:6327055"
FT /id="VAR_060727"
FT VARIANT 51
FT /note="K -> R (in dbSNP:rs8052394)"
FT /id="VAR_059436"
SQ SEQUENCE 61 AA; 6120 MW; 8FBA7C54EE8B6A13 CRC64;
MDPNCSCATG GSCTCTGSCK CKECKCTSCK KSCCSCCPMS CAKCAQGCIC KGASEKCSCC
A
//
