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Protein

Metallothionein-3

Gene

MT3

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

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

  • antioxidant activity Source: UniProtKB
  • cadmium ion binding Source: UniProtKB
  • copper ion binding Source: UniProtKB
  • cysteine-type endopeptidase inhibitor activity involved in apoptotic process Source: UniProtKB
  • drug binding Source: UniProtKB
  • protein kinase activator activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • activation of protein kinase B activity Source: UniProtKB
  • astrocyte development Source: UniProtKB
  • cadmium ion homeostasis Source: UniProtKB
  • cell proliferation Source: ProtInc
  • cellular lipid catabolic process Source: UniProtKB
  • cellular metal ion homeostasis Source: UniProtKB
  • cellular response to cadmium ion Source: UniProtKB
  • cellular response to drug Source: UniProtKB
  • cellular response to hypoxia Source: UniProtKB
  • cellular response to nitric oxide Source: UniProtKB
  • cellular response to oxidative stress Source: UniProtKB
  • cellular zinc ion homeostasis Source: UniProtKB
  • cholesterol catabolic process Source: UniProtKB
  • energy reserve metabolic process Source: UniProtKB
  • ERK1 and ERK2 cascade Source: UniProtKB
  • histone modification Source: UniProtKB
  • leptin-mediated signaling pathway Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of autophagy Source: UniProtKB
  • negative regulation of axon extension Source: UniProtKB
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cysteine-type endopeptidase activity Source: UniProtKB
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • negative regulation of necrotic cell death Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • negative regulation of oxidoreductase activity Source: UniProtKB
  • negative regulation of reactive oxygen species metabolic process Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of catalytic activity Source: UniProtKB
  • positive regulation of cell death Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of lysosomal membrane permeability Source: UniProtKB
  • positive regulation of necrotic cell death Source: UniProtKB
  • positive regulation of oxygen metabolic process Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: UniProtKB
  • positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  • protein import into nucleus, translocation Source: UniProtKB
  • protein kinase B signaling Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of protein glycosylation Source: UniProtKB
  • regulation of response to food Source: UniProtKB
  • removal of superoxide radicals Source: UniProtKB
  • response to hypoxia Source: UniProtKB
  • zinc II ion transport Source: UniProtKB
  • zinc ion homeostasis Source: UniProtKB
Complete GO annotation...

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 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:7408. MT3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • inclusion body Source: UniProtKB
  • intracellular Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • synaptic vesicle Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31216.

Polymorphism and mutation databases

BioMutaiMT3.
DMDMi127404.

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

BgeeiP25713.
CleanExiHS_MT3.
ExpressionAtlasiP25713. baseline and differential.
GenevisibleiP25713. HS.

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 – 383Combined sources
Helixi44 – 474Combined sources
Helixi50 – 534Combined sources
Turni55 – 595Combined sources
Beta strandi60 – 623Combined sources
Turni65 – 673Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00730000111484.
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

        10         20         30         40         50
MDPETCPCPS GGSCTCADSC KCEGCKCTSC KKSCCSCCPA ECEKCAKDCV
60
CKGGEAAEAE AEKCSCCQ
Length:68
Mass (Da):6,927
Last modified:May 1, 1992 - v1
Checksum:i59801ECF5BC8A406
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

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

Chemistry

BindingDBiP25713.

PTM databases

PhosphoSiteiP25713.

Polymorphism and mutation databases

BioMutaiMT3.
DMDMi127404.

Proteomic databases

PaxDbiP25713.
PRIDEiP25713.

Protocols and materials databases

DNASUi4504.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4504.
GeneCardsiGC16P056623.
HGNCiHGNC:7408. MT3.
HPAiCAB017779.
HPA004011.
MIMi139255. gene.
neXtProtiNX_P25713.
PharmGKBiPA31216.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG132957.
GeneTreeiENSGT00730000111484.
HOGENOMiHOG000236262.
InParanoidiP25713.
KOiK14740.
PhylomeDBiP25713.

Miscellaneous databases

EvolutionaryTraceiP25713.
GeneWikiiMT3.
GenomeRNAii4504.
NextBioi17412.
PROiP25713.
SOURCEiSearch...

Gene expression databases

BgeeiP25713.
CleanExiHS_MT3.
ExpressionAtlasiP25713. baseline and differential.
GenevisibleiP25713. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 145 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.