ID MT3_HUMAN Reviewed; 68 AA. AC P25713; Q2V574; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1992, sequence version 1. DT 04-NOV-2026, entry version 209. DE RecName: Full=Metallothionein-3; DE Short=MT-3; DE AltName: Full=GIFB; DE Short=GIF; DE AltName: Full=Growth inhibitory factor; DE AltName: Full=Metallothionein-III; DE Short=MT-III; GN Name=MT3; 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 PROTEIN SEQUENCE, AND ACETYLATION AT MET-1. RC TISSUE=Brain; RX PubMed=1873033; DOI=10.1016/0896-6273(91)90272-2; RA Uchida Y., Takio K., Titani K., Ihara Y., Tomonaga M.; RT "The growth inhibitory factor that is deficient in the Alzheimer's disease RT brain is a 68 amino acid metallothionein-like protein."; RL Neuron 7:337-347(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Brain; RX PubMed=1631128; DOI=10.1073/pnas.89.14.6333; RA Palmiter R.D., Findley S.D., Whitmore T.E., Durnam D.M.; RT "MT-III, a brain-specific member of the metallothionein gene family."; RL Proc. Natl. Acad. Sci. U.S.A. 89:6333-6337(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1464312; DOI=10.1002/j.1460-2075.1992.tb05590.x; RA Tsuji S., Kobayashi H., Uchida Y., Ihara Y., Miyatake T.; RT "Molecular cloning of human growth inhibitory factor cDNA and its down- RT regulation in Alzheimer's disease."; RL EMBO J. 11:4843-4850(1992). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8039715; DOI=10.1016/0378-1119(94)90391-3; RA Naruse S., Igarashi S., Furuya T., Kobayashi H., Miyatake T., Tsuji S.; RT "Structures of the human and mouse growth inhibitory factor-encoding RT genes."; RL Gene 144:283-287(1994). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7677777; DOI=10.1006/bbrc.1995.2334; RA Amoureux M.C., Wurch T., Pauwels P.J.; RT "Modulation of metallothionein-III mRNA content and growth rate of rat C6- RT glial cells by transfection with human 5-HT1D receptor genes."; RL Biochem. Biophys. Res. Commun. 214:639-645(1995). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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). RN [9] {ECO:0007744|PDB:2FJ4, ECO:0007744|PDB:2FJ5} RP STRUCTURE BY NMR OF 32-68. RA Wu H., Zhang Q.; RT "Solution structure of a-domain of HUMAN Metallothionein-3 (MT-3)."; RL Submitted (DEC-2005) to the PDB data bank. RN [10] {ECO:0007744|PDB:2F5H} RP STRUCTURE BY NMR OF 32-68 IN COMPLEX WITH CADMIUM IONS. RX PubMed=16413543; DOI=10.1016/j.febslet.2005.12.099; RA Wang H., Zhang Q., Cai B., Li H., Sze K.H., Huang Z.X., Wu H.M., Sun H.; RT "Solution structure and dynamics of human metallothionein-3 (MT-3)."; RL FEBS Lett. 580:795-800(2006). CC -!- FUNCTION: Binds heavy metals. Contains three zinc and three copper CC atoms per polypeptide chain and only a negligible amount of cadmium. CC Inhibits survival and neurite formation of cortical neurons in vitro. CC -!- INTERACTION: CC P25713; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-8084264, EBI-750109; CC P25713; P02766: TTR; NbExp=3; IntAct=EBI-8084264, EBI-711909; CC -!- TISSUE SPECIFICITY: Abundant in a subset of astrocytes in the normal CC human brain, but greatly reduced in the Alzheimer disease (AD) brain. CC -!- SIMILARITY: Belongs to the metallothionein superfamily. Type 1 family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M93311; AAA36214.1; -; Genomic_DNA. DR EMBL; D13365; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; S72043; AAB31396.1; -; Genomic_DNA. DR EMBL; X89604; CAA61763.1; -; mRNA. DR EMBL; BT007030; AAP35677.1; -; mRNA. DR EMBL; DQ297144; ABB84467.1; -; Genomic_DNA. DR EMBL; BC013081; AAH13081.1; -; mRNA. DR CCDS; CCDS10762.1; -. DR PIR; B46034; B46034. DR RefSeq; NP_005945.1; NM_005954.4. DR PDB; 2F5H; NMR; -; A=32-68. DR PDB; 2FJ4; NMR; -; A=32-68. DR PDB; 2FJ5; NMR; -; A=32-68. DR AlphaFoldDB; P25713; -. DR SMR; P25713; -. DR BioGRID; 110610; 8. DR FunCoup; P25713; 1. DR IntAct; P25713; 2. DR NDEx; IQUERY-CP-MT3; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000200691; -. DR DrugBank; DB09130; Copper. 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; P25713; -. DR PhosphoSitePlus; P25713; -. DR BioMuta; MT3; -. DR DMDM; 127404; -. DR MassIVE; P25713; -. DR PaxDb; 9606-ENSP00000200691; -. DR PeptideAtlas; P25713; -. DR ProteomicsDB; 54284; -. DR Antibodypedia; 1293; 169 antibodies from 21 providers. DR DNASU; 4504; -. DR Ensembl; ENST00000200691.5; ENSP00000200691.5; ENSG00000087250.10. DR GeneID; 4504; -. DR KEGG; hsa:4504; -. DR MANE-Select; ENST00000200691.5; ENSP00000200691.5; NM_005954.4; NP_005945.1. DR UCSC; uc002ejf.4; human. DR AGR; HGNC:7408; -. DR ClinPGx; PA31216; -. DR CTD; 4504; -. DR DisGeNET; 4504; -. DR GeneCards; MT3; -. DR HGNC; HGNC:7408; MT3. DR HPA; ENSG00000087250; Tissue enriched (brain). DR MIM; 139255; gene. DR OpenTargets; ENSG00000087250; -. DR VEuPathDB; HostDB:ENSG00000087250; -. DR eggNOG; KOG4738; Eukaryota. DR GeneTree; ENSGT00950000182967; -. DR HOGENOM; CLU_171204_2_0_1; -. DR InParanoid; P25713; -. DR OMA; AKDCVCT; -. DR OrthoDB; 9539597at2759; -. DR PAN-GO; P25713; 9 GO annotations based on evolutionary models. DR PhylomeDB; P25713; -. DR PathwayCommons; P25713; -. DR Reactome; R-HSA-5661231; Metallothioneins bind metals. DR SignaLink; P25713; -. DR Agora; ENSG00000087250; -. DR BioGRID-ORCS; 4504; 12 hits in 1143 CRISPR screens. DR ChiTaRS; MT3; human. DR EvolutionaryTrace; P25713; -. DR GeneWiki; MT3; -. DR GenomeRNAi; 4504; -. DR Pharos; P25713; Tbio. DR PRO; PR:P25713; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P25713; protein. DR Bgee; ENSG00000087250; Expressed in nucleus accumbens and 109 other cell types or tissues. DR ExpressionAtlas; P25713; baseline and differential. DR GO; GO:0097450; C:astrocyte end-foot; IEA:Ensembl. DR GO; GO:0030424; C:axon; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; IEA:Ensembl. DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB. DR GO; GO:0005874; C:microtubule; IEA:Ensembl. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0005840; C:ribosome; IEA:Ensembl. DR GO; GO:0008021; C:synaptic vesicle; ISS:UniProtKB. DR GO; GO:0016209; F:antioxidant activity; NAS:UniProtKB. DR GO; GO:0046870; F:cadmium ion binding; IDA:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IBA:GO_Central. DR GO; GO:0030295; F:protein kinase activator activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0032148; P:activation of protein kinase B activity; IDA:UniProtKB. DR GO; GO:1990748; P:cellular detoxification; IDA:UniProtKB. DR GO; GO:0071276; P:cellular response to cadmium ion; IBA:GO_Central. DR GO; GO:0071280; P:cellular response to copper ion; IBA:GO_Central. DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB. DR GO; GO:0034599; P:cellular response to oxidative stress; IEP:UniProtKB. DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:GO_Central. DR GO; GO:0071294; P:cellular response to zinc ion; IBA:GO_Central. DR GO; GO:0071585; P:detoxification of cadmium ion; IEA:Ensembl. DR GO; GO:0010273; P:detoxification of copper ion; IBA:GO_Central. DR GO; GO:0030003; P:intracellular monoatomic cation homeostasis; TAS:UniProtKB. DR GO; GO:0006882; P:intracellular zinc ion homeostasis; ISS:UniProtKB. DR GO; GO:0030517; P:negative regulation of axon extension; IDA:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB. DR GO; GO:2000296; P:negative regulation of hydrogen peroxide catabolic process; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB. DR GO; GO:0010977; P:negative regulation of neuron projection development; TAS:GO_Central. DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB. DR GO; GO:0019430; P:removal of superoxide radicals; IDA:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0006829; P:zinc ion transport; ISS:UniProtKB. DR FunFam; 4.10.10.10:FF:000001; Metallothionein; 1. 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:SF18; METALLOTHIONEIN-3; 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 3D-structure; Acetylation; Copper; Direct protein sequencing; KW Metal-binding; Metal-thiolate cluster; Phosphoprotein; KW Proteomics identification; Reference proteome; Zinc. FT CHAIN 1..68 FT /note="Metallothionein-3" FT /id="PRO_0000197250" FT REGION 1..30 FT /note="Beta" FT REGION 31..68 FT /note="Alpha" FT BINDING 6 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 8 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 8 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 14 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 16 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 16 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 20 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 22 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 25 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 25 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 27 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 30 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 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 35 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 35 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 38 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 38 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 42 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 45 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 45 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 49 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 51 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 51 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 64 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 66 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 67 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT BINDING 67 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:0000269|PubMed:16413543, FT ECO:0007744|PDB:2F5H" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000269|PubMed:1873033" FT MOD_RES 33 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28184" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:2F5H" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:2F5H" FT HELIX 50..53 FT /evidence="ECO:0007829|PDB:2FJ4" FT TURN 55..59 FT /evidence="ECO:0007829|PDB:2FJ4" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:2FJ4" FT TURN 65..67 FT /evidence="ECO:0007829|PDB:2FJ4" SQ SEQUENCE 68 AA; 6927 MW; 59801ECF5BC8A406 CRC64; MDPETCPCPS GGSCTCADSC KCEGCKCTSC KKSCCSCCPA ECEKCAKDCV CKGGEAAEAE AEKCSCCQ //