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P25713

- MT3_HUMAN

UniProt

P25713 - MT3_HUMAN

Protein

Metallothionein-3

Gene

MT3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi6 – 61Divalent metal cation; cluster BBy similarity
    Metal bindingi8 – 81Divalent metal cation; cluster BBy similarity
    Metal bindingi14 – 141Divalent metal cation; cluster BBy similarity
    Metal bindingi16 – 161Divalent metal cation; cluster BBy similarity
    Metal bindingi20 – 201Divalent metal cation; cluster BBy similarity
    Metal bindingi22 – 221Divalent metal cation; cluster BBy similarity
    Metal bindingi25 – 251Divalent metal cation; cluster BBy similarity
    Metal bindingi27 – 271Divalent metal cation; cluster BBy similarity
    Metal bindingi30 – 301Divalent metal cation; cluster BBy similarity
    Metal bindingi34 – 341Divalent metal cation; cluster ABy similarity
    Metal bindingi35 – 351Divalent metal cation; cluster ABy similarity
    Metal bindingi37 – 371Divalent metal cation; cluster ABy similarity
    Metal bindingi38 – 381Divalent metal cation; cluster ABy similarity
    Metal bindingi42 – 421Divalent metal cation; cluster ABy similarity
    Metal bindingi45 – 451Divalent metal cation; cluster ABy similarity
    Metal bindingi49 – 491Divalent metal cation; cluster ABy similarity
    Metal bindingi51 – 511Divalent metal cation; cluster ABy similarity
    Metal bindingi64 – 641Divalent metal cation; cluster ABy similarity
    Metal bindingi66 – 661Divalent metal cation; cluster ABy similarity
    Metal bindingi67 – 671Divalent metal cation; cluster ABy similarity

    GO - Molecular functioni

    1. antioxidant activity Source: UniProtKB
    2. cadmium ion binding Source: UniProtKB
    3. copper ion binding Source: UniProtKB
    4. cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
    5. drug binding Source: UniProtKB
    6. protein binding Source: UniProtKB
    7. protein kinase activator activity Source: UniProtKB
    8. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. activation of protein kinase B activity Source: UniProtKB
    2. astrocyte development Source: UniProtKB
    3. cadmium ion homeostasis Source: UniProtKB
    4. cell proliferation Source: ProtInc
    5. cellular lipid catabolic process Source: UniProtKB
    6. cellular metal ion homeostasis Source: UniProtKB
    7. cellular response to cadmium ion Source: UniProtKB
    8. cellular response to drug Source: UniProtKB
    9. cellular response to hypoxia Source: UniProtKB
    10. cellular response to nitric oxide Source: UniProtKB
    11. cellular response to oxidative stress Source: UniProtKB
    12. cellular zinc ion homeostasis Source: UniProtKB
    13. cholesterol catabolic process Source: UniProtKB
    14. energy reserve metabolic process Source: UniProtKB
    15. ERK1 and ERK2 cascade Source: UniProtKB
    16. histone modification Source: UniProtKB
    17. leptin-mediated signaling pathway Source: UniProtKB
    18. negative regulation of apoptotic process Source: UniProtKB
    19. negative regulation of autophagy Source: UniProtKB
    20. negative regulation of axon extension Source: UniProtKB
    21. negative regulation of cell growth Source: UniProtKB
    22. negative regulation of cysteine-type endopeptidase activity Source: UniProtKB
    23. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    24. negative regulation of necrotic cell death Source: UniProtKB
    25. negative regulation of neuron apoptotic process Source: UniProtKB
    26. negative regulation of oxidoreductase activity Source: UniProtKB
    27. negative regulation of reactive oxygen species metabolic process Source: UniProtKB
    28. negative regulation of transcription, DNA-templated Source: UniProtKB
    29. positive regulation of catalytic activity Source: UniProtKB
    30. positive regulation of cell death Source: UniProtKB
    31. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    32. positive regulation of gene expression Source: UniProtKB
    33. positive regulation of lysosomal membrane permeability Source: UniProtKB
    34. positive regulation of necrotic cell death Source: UniProtKB
    35. positive regulation of oxygen metabolic process Source: UniProtKB
    36. positive regulation of protein phosphorylation Source: UniProtKB
    37. positive regulation of transcription, DNA-templated Source: UniProtKB
    38. positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: UniProtKB
    39. positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
    40. protein import into nucleus, translocation Source: UniProtKB
    41. protein kinase B signaling Source: UniProtKB
    42. protein stabilization Source: UniProtKB
    43. regulation of protein glycosylation Source: UniProtKB
    44. regulation of response to food Source: UniProtKB
    45. removal of superoxide radicals Source: UniProtKB
    46. response to hypoxia Source: UniProtKB
    47. zinc ion homeostasis Source: UniProtKB
    48. zinc ion transport Source: UniProtKB

    Keywords - Ligandi

    Copper, Metal-binding, Metal-thiolate cluster, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Metallothionein-3
    Short name:
    MT-3
    Alternative name(s):
    GIFB
    Short name:
    GIF
    Growth inhibitory factor
    Metallothionein-III
    Short name:
    MT-III
    Gene namesi
    Name:MT3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:7408. MT3.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. inclusion body Source: UniProtKB
    3. intracellular Source: UniProtKB
    4. perinuclear region of cytoplasm Source: UniProtKB
    5. synaptic vesicle Source: UniProtKB

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA31216.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 6868Metallothionein-3PRO_0000197250Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiP25713.
    PRIDEiP25713.

    PTM databases

    PhosphoSiteiP25713.

    Expressioni

    Tissue specificityi

    Abundant in a subset of astrocytes in the normal human brain, but greatly reduced in the Alzheimer disease (AD) brain.

    Gene expression databases

    ArrayExpressiP25713.
    BgeeiP25713.
    CleanExiHS_MT3.
    GenevestigatoriP25713.

    Organism-specific databases

    HPAiCAB017779.
    HPA004011.

    Interactioni

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TTRP027663EBI-8084264,EBI-711909

    Protein-protein interaction databases

    BioGridi110610. 2 interactions.
    IntActiP25713. 1 interaction.
    MINTiMINT-7905812.
    STRINGi9606.ENSP00000200691.

    Structurei

    Secondary structure

    1
    68
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi36 – 383
    Helixi44 – 474
    Helixi50 – 534
    Turni55 – 595
    Beta strandi60 – 623
    Turni65 – 673

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2F5HNMR-A32-68[»]
    2FJ4NMR-A32-68[»]
    2FJ5NMR-A32-68[»]
    ProteinModelPortaliP25713.
    SMRiP25713. Positions 32-68.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP25713.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 3030BetaAdd
    BLAST
    Regioni31 – 6838AlphaAdd
    BLAST

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG132957.
    HOGENOMiHOG000236262.
    InParanoidiP25713.
    KOiK14740.
    PhylomeDBiP25713.

    Family and domain databases

    Gene3Di4.10.10.10. 1 hit.
    InterProiIPR017854. Metalthion_dom.
    IPR023587. Metalthion_dom_vert.
    IPR003019. Metalthion_sfam_euk.
    IPR000006. Metalthion_vert.
    IPR018064. Metalthion_vert_metal_BS.
    [Graphical view]
    PANTHERiPTHR23299. PTHR23299. 1 hit.
    PfamiPF00131. Metallothio. 1 hit.
    [Graphical view]
    PRINTSiPR00860. MTVERTEBRATE.
    SUPFAMiSSF57868. SSF57868. 1 hit.
    PROSITEiPS00203. METALLOTHIONEIN_VRT. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P25713-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDPETCPCPS GGSCTCADSC KCEGCKCTSC KKSCCSCCPA ECEKCAKDCV   50
    CKGGEAAEAE AEKCSCCQ 68
    Length:68
    Mass (Da):6,927
    Last modified:May 1, 1992 - v1
    Checksum:i59801ECF5BC8A406
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M93311 Genomic DNA. Translation: AAA36214.1.
    D13365 mRNA. No translation available.
    S72043 Genomic DNA. Translation: AAB31396.1.
    X89604 mRNA. Translation: CAA61763.1.
    BT007030 mRNA. Translation: AAP35677.1.
    DQ297144 Genomic DNA. Translation: ABB84467.1.
    BC013081 mRNA. Translation: AAH13081.1.
    CCDSiCCDS10762.1.
    PIRiB46034.
    RefSeqiNP_005945.1. NM_005954.2.
    UniGeneiHs.73133.

    Genome annotation databases

    EnsembliENST00000200691; ENSP00000200691; ENSG00000087250.
    GeneIDi4504.
    KEGGihsa:4504.
    UCSCiuc002ejf.3. human.

    Polymorphism databases

    DMDMi127404.

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M93311 Genomic DNA. Translation: AAA36214.1 .
    D13365 mRNA. No translation available.
    S72043 Genomic DNA. Translation: AAB31396.1 .
    X89604 mRNA. Translation: CAA61763.1 .
    BT007030 mRNA. Translation: AAP35677.1 .
    DQ297144 Genomic DNA. Translation: ABB84467.1 .
    BC013081 mRNA. Translation: AAH13081.1 .
    CCDSi CCDS10762.1.
    PIRi B46034.
    RefSeqi NP_005945.1. NM_005954.2.
    UniGenei Hs.73133.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2F5H NMR - A 32-68 [» ]
    2FJ4 NMR - A 32-68 [» ]
    2FJ5 NMR - A 32-68 [» ]
    ProteinModelPortali P25713.
    SMRi P25713. Positions 32-68.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110610. 2 interactions.
    IntActi P25713. 1 interaction.
    MINTi MINT-7905812.
    STRINGi 9606.ENSP00000200691.

    Chemistry

    BindingDBi P25713.

    PTM databases

    PhosphoSitei P25713.

    Polymorphism databases

    DMDMi 127404.

    Proteomic databases

    PaxDbi P25713.
    PRIDEi P25713.

    Protocols and materials databases

    DNASUi 4504.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000200691 ; ENSP00000200691 ; ENSG00000087250 .
    GeneIDi 4504.
    KEGGi hsa:4504.
    UCSCi uc002ejf.3. human.

    Organism-specific databases

    CTDi 4504.
    GeneCardsi GC16P056623.
    HGNCi HGNC:7408. MT3.
    HPAi CAB017779.
    HPA004011.
    MIMi 139255. gene.
    neXtProti NX_P25713.
    PharmGKBi PA31216.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG132957.
    HOGENOMi HOG000236262.
    InParanoidi P25713.
    KOi K14740.
    PhylomeDBi P25713.

    Miscellaneous databases

    EvolutionaryTracei P25713.
    GeneWikii MT3.
    GenomeRNAii 4504.
    NextBioi 17412.
    PROi P25713.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P25713.
    Bgeei P25713.
    CleanExi HS_MT3.
    Genevestigatori P25713.

    Family and domain databases

    Gene3Di 4.10.10.10. 1 hit.
    InterProi IPR017854. Metalthion_dom.
    IPR023587. Metalthion_dom_vert.
    IPR003019. Metalthion_sfam_euk.
    IPR000006. Metalthion_vert.
    IPR018064. Metalthion_vert_metal_BS.
    [Graphical view ]
    PANTHERi PTHR23299. PTHR23299. 1 hit.
    Pfami PF00131. Metallothio. 1 hit.
    [Graphical view ]
    PRINTSi PR00860. MTVERTEBRATE.
    SUPFAMi SSF57868. SSF57868. 1 hit.
    PROSITEi PS00203. METALLOTHIONEIN_VRT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein."
      Uchida Y., Takio K., Titani K., Ihara Y., Tomonaga M.
      Neuron 7:337-347(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE, ACETYLATION AT MET-1.
      Tissue: Brain.
    2. "MT-III, a brain-specific member of the metallothionein gene family."
      Palmiter R.D., Findley S.D., Whitmore T.E., Durnam D.M.
      Proc. Natl. Acad. Sci. U.S.A. 89:6333-6337(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Brain.
    3. "Molecular cloning of human growth inhibitory factor cDNA and its down-regulation in Alzheimer's disease."
      Tsuji S., Kobayashi H., Uchida Y., Ihara Y., Miyatake T.
      EMBO J. 11:4843-4850(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Structures of the human and mouse growth inhibitory factor-encoding genes."
      Naruse S., Igarashi S., Furuya T., Kobayashi H., Miyatake T., Tsuji S.
      Gene 144:283-287(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "Modulation of metallothionein-III mRNA content and growth rate of rat C6-glial cells by transfection with human 5-HT1D receptor genes."
      Amoureux M.C., Wurch T., Pauwels P.J.
      Biochem. Biophys. Res. Commun. 214:639-645(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    6. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    7. NIEHS SNPs program
      Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.

    Entry informationi

    Entry nameiMT3_HUMAN
    AccessioniPrimary (citable) accession number: P25713
    Secondary accession number(s): Q2V574
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 1, 1992
    Last sequence update: May 1, 1992
    Last modified: October 1, 2014
    This is version 139 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Metallothioneins
      Classification of metallothioneins and list of entries
    3. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3