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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)DescriptionActionsGraphical viewLength
Metal bindingi6Divalent metal cation; cluster BBy similarity1
Metal bindingi8Divalent metal cation; cluster BBy similarity1
Metal bindingi14Divalent metal cation; cluster BBy similarity1
Metal bindingi16Divalent metal cation; cluster BBy similarity1
Metal bindingi20Divalent metal cation; cluster BBy similarity1
Metal bindingi22Divalent metal cation; cluster BBy similarity1
Metal bindingi25Divalent metal cation; cluster BBy similarity1
Metal bindingi27Divalent metal cation; cluster BBy similarity1
Metal bindingi30Divalent metal cation; cluster BBy similarity1
Metal bindingi34Divalent metal cation; cluster ABy similarity1
Metal bindingi35Divalent metal cation; cluster ABy similarity1
Metal bindingi37Divalent metal cation; cluster ABy similarity1
Metal bindingi38Divalent metal cation; cluster ABy similarity1
Metal bindingi42Divalent metal cation; cluster ABy similarity1
Metal bindingi45Divalent metal cation; cluster ABy similarity1
Metal bindingi49Divalent metal cation; cluster ABy similarity1
Metal bindingi51Divalent metal cation; cluster ABy similarity1
Metal bindingi64Divalent metal cation; cluster ABy similarity1
Metal bindingi66Divalent metal cation; cluster ABy similarity1
Metal bindingi67Divalent metal cation; cluster ABy similarity1

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
  • brain development Source: Ensembl
  • 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 hydrogen peroxide catabolic process Source: Ensembl
  • 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
  • response to metal ion Source: Reactome
  • zinc II ion transport Source: UniProtKB
  • zinc ion homeostasis Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000087250-MONOMER.
ReactomeiR-HSA-5661231. Metallothioneins bind metals.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:7408. MT3.

Subcellular locationi

GO - Cellular componenti

  • astrocyte end-foot Source: Ensembl
  • axon Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • dendritic spine Source: Ensembl
  • extracellular space Source: Ensembl
  • inclusion body Source: UniProtKB
  • intracellular Source: UniProtKB
  • microtubule Source: Ensembl
  • mitochondrial outer membrane Source: Ensembl
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: Ensembl
  • postsynaptic density Source: Ensembl
  • ribosome Source: Ensembl
  • rough endoplasmic reticulum Source: Ensembl
  • synaptic vesicle Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi4504.
OpenTargetsiENSG00000087250.
PharmGKBiPA31216.

Polymorphism and mutation databases

BioMutaiMT3.
DMDMi127404.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001972501 – 68Metallothionein-3Add BLAST68

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionine1 Publication1
Modified residuei33PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP25713.
PaxDbiP25713.
PeptideAtlasiP25713.
PRIDEiP25713.

PTM databases

PhosphoSitePlusiP25713.

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

BgeeiENSG00000087250.
CleanExiHS_MT3.
ExpressionAtlasiP25713. baseline and differential.

Organism-specific databases

HPAiCAB017779.
HPA004011.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF2IPQ9NYB02EBI-8084264,EBI-750109
TTRP027663EBI-8084264,EBI-711909

Protein-protein interaction databases

BioGridi110610. 2 interactors.
IntActiP25713. 2 interactors.
MINTiMINT-7905812.
STRINGi9606.ENSP00000200691.

Structurei

Secondary structure

168
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi36 – 38Combined sources3
Helixi44 – 47Combined sources4
Helixi50 – 53Combined sources4
Turni55 – 59Combined sources5
Beta strandi60 – 62Combined sources3
Turni65 – 67Combined sources3

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP25713.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 30BetaAdd BLAST30
Regioni31 – 68AlphaAdd BLAST38

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410KFJ7. Eukaryota.
ENOG4110T98. LUCA.
GeneTreeiENSGT00730000111484.
HOGENOMiHOG000236262.
InParanoidiP25713.
KOiK14740.
PhylomeDBiP25713.

Family and domain databases

Gene3Di4.10.10.10. 1 hit.
InterProiIPR003019. Metalthion.
IPR017854. Metalthion_dom.
IPR023587. Metalthion_dom_vert.
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.4. 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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2F5HNMR-A32-68[»]
2FJ4NMR-A32-68[»]
2FJ5NMR-A32-68[»]
ProteinModelPortaliP25713.
SMRiP25713.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110610. 2 interactors.
IntActiP25713. 2 interactors.
MINTiMINT-7905812.
STRINGi9606.ENSP00000200691.

PTM databases

PhosphoSitePlusiP25713.

Polymorphism and mutation databases

BioMutaiMT3.
DMDMi127404.

Proteomic databases

EPDiP25713.
PaxDbiP25713.
PeptideAtlasiP25713.
PRIDEiP25713.

Protocols and materials databases

DNASUi4504.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000200691; ENSP00000200691; ENSG00000087250.
GeneIDi4504.
KEGGihsa:4504.
UCSCiuc002ejf.4. human.

Organism-specific databases

CTDi4504.
DisGeNETi4504.
GeneCardsiMT3.
HGNCiHGNC:7408. MT3.
HPAiCAB017779.
HPA004011.
MIMi139255. gene.
neXtProtiNX_P25713.
OpenTargetsiENSG00000087250.
PharmGKBiPA31216.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410KFJ7. Eukaryota.
ENOG4110T98. LUCA.
GeneTreeiENSGT00730000111484.
HOGENOMiHOG000236262.
InParanoidiP25713.
KOiK14740.
PhylomeDBiP25713.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000087250-MONOMER.
ReactomeiR-HSA-5661231. Metallothioneins bind metals.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000087250.
CleanExiHS_MT3.
ExpressionAtlasiP25713. baseline and differential.

Family and domain databases

Gene3Di4.10.10.10. 1 hit.
InterProiIPR003019. Metalthion.
IPR017854. Metalthion_dom.
IPR023587. Metalthion_dom_vert.
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...

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: November 2, 2016
This is version 157 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

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 one 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.