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
//