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P25713 (MT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Metallothionein-3

Short name=MT-3
Alternative name(s):
GIFB
Short name=GIF
Growth inhibitory factor
Metallothionein-III
Short name=MT-III
Gene names
Name:MT3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length68 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Tissue specificity

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

Sequence similarities

Belongs to the metallothionein superfamily. Type 1 family.

Ontologies

Keywords
   LigandCopper
Metal-binding
Metal-thiolate cluster
Zinc
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processERK1 and ERK2 cascade

Inferred from direct assay PubMed 18554677. Source: UniProtKB

activation of protein kinase B activity

Inferred from direct assay PubMed 18295594. Source: UniProtKB

astrocyte development

Inferred from sequence or structural similarity. Source: UniProtKB

cadmium ion homeostasis

Inferred from direct assay PubMed 18157556. Source: UniProtKB

cell proliferation

Traceable author statement Ref.1. Source: ProtInc

cellular lipid catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

cellular metal ion homeostasis

Non-traceable author statement PubMed 12383939. Source: UniProtKB

cellular response to cadmium ion

Inferred from direct assay PubMed 16387743. Source: UniProtKB

cellular response to drug

Inferred from direct assay PubMed 19536566. Source: UniProtKB

cellular response to hypoxia

Inferred from expression pattern PubMed 18206644. Source: UniProtKB

cellular response to nitric oxide

Inferred from direct assay PubMed 18157556. Source: UniProtKB

cellular response to oxidative stress

Inferred from expression pattern PubMed 20039155. Source: UniProtKB

cellular zinc ion homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

cholesterol catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

energy reserve metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

histone modification

Inferred from mutant phenotype PubMed 21818286. Source: UniProtKB

leptin-mediated signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from direct assay PubMed 15129022PubMed 18554677. Source: UniProtKB

negative regulation of autophagy

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of axon extension

Inferred from direct assay PubMed 16601975PubMed 17712581. Source: UniProtKB

negative regulation of cell growth

Inferred from direct assay PubMed 16601975PubMed 17712581. Source: UniProtKB

negative regulation of cysteine-type endopeptidase activity

Inferred from direct assay PubMed 18554677. Source: UniProtKB

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 16387743. Source: UniProtKB

negative regulation of necrotic cell death

Inferred from direct assay PubMed 18554677. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of oxidoreductase activity

Inferred from direct assay PubMed 21320589. Source: UniProtKB

negative regulation of reactive oxygen species metabolic process

Inferred from direct assay PubMed 18554677. Source: UniProtKB

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay PubMed 18295594. Source: UniProtKB

positive regulation of catalytic activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell death

Inferred from direct assay PubMed 16387743. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 18295594. Source: UniProtKB

positive regulation of lysosomal membrane permeability

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of necrotic cell death

Inferred from direct assay PubMed 15129022PubMed 16387743. Source: UniProtKB

positive regulation of oxygen metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 18295594. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress

Inferred from direct assay PubMed 18554677. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18295594. Source: UniProtKB

positive regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from direct assay PubMed 18295594. Source: UniProtKB

protein import into nucleus, translocation

Inferred from direct assay PubMed 18554677. Source: UniProtKB

protein kinase B signaling

Inferred from direct assay PubMed 18554677. Source: UniProtKB

protein stabilization

Inferred from direct assay PubMed 18295594. Source: UniProtKB

regulation of protein glycosylation

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of response to food

Inferred from sequence or structural similarity. Source: UniProtKB

removal of superoxide radicals

Inferred from direct assay PubMed 12383939. Source: UniProtKB

response to hypoxia

Inferred from direct assay PubMed 12763630. Source: UniProtKB

zinc ion homeostasis

Inferred from direct assay PubMed 18157556. Source: UniProtKB

zinc ion transport

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10355541. Source: UniProtKB

inclusion body

Inferred from direct assay PubMed 20039155. Source: UniProtKB

intracellular

Inferred from direct assay PubMed 21818286. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay PubMed 20039155. Source: UniProtKB

synaptic vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionantioxidant activity

Non-traceable author statement PubMed 12383939. Source: UniProtKB

cadmium ion binding

Inferred from direct assay PubMed 16601975PubMed 17712581PubMed 18157556. Source: UniProtKB

copper ion binding

Inferred from direct assay PubMed 21320589. Source: UniProtKB

cysteine-type endopeptidase inhibitor activity involved in apoptotic process

Inferred from direct assay PubMed 16387743. Source: UniProtKB

drug binding

Inferred from direct assay PubMed 19536566. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 21320589. Source: UniProtKB

protein kinase activator activity

Inferred from direct assay PubMed 18295594. Source: UniProtKB

zinc ion binding

Inferred from direct assay PubMed 17712581PubMed 19536566PubMed 21320589. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TTRP027663EBI-8084264,EBI-711909

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 6868Metallothionein-3
PRO_0000197250

Regions

Region1 – 3030Beta
Region31 – 6838Alpha

Sites

Metal binding61Divalent metal cation; cluster B By similarity
Metal binding81Divalent metal cation; cluster B By similarity
Metal binding141Divalent metal cation; cluster B By similarity
Metal binding161Divalent metal cation; cluster B By similarity
Metal binding201Divalent metal cation; cluster B By similarity
Metal binding221Divalent metal cation; cluster B By similarity
Metal binding251Divalent metal cation; cluster B By similarity
Metal binding271Divalent metal cation; cluster B By similarity
Metal binding301Divalent metal cation; cluster B By similarity
Metal binding341Divalent metal cation; cluster A By similarity
Metal binding351Divalent metal cation; cluster A By similarity
Metal binding371Divalent metal cation; cluster A By similarity
Metal binding381Divalent metal cation; cluster A By similarity
Metal binding421Divalent metal cation; cluster A By similarity
Metal binding451Divalent metal cation; cluster A By similarity
Metal binding491Divalent metal cation; cluster A By similarity
Metal binding511Divalent metal cation; cluster A By similarity
Metal binding641Divalent metal cation; cluster A By similarity
Metal binding661Divalent metal cation; cluster A By similarity
Metal binding671Divalent metal cation; cluster A By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.1

Secondary structure

............ 68
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P25713 [UniParc].

Last modified May 1, 1992. Version 1.
Checksum: 59801ECF5BC8A406

FASTA686,927
        10         20         30         40         50         60 
MDPETCPCPS GGSCTCADSC KCEGCKCTSC KKSCCSCCPA ECEKCAKDCV CKGGEAAEAE 


AEKCSCCQ 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10762.1.
PIRB46034.
RefSeqNP_005945.1. NM_005954.2.
UniGeneHs.73133.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2F5HNMR-A32-68[»]
2FJ4NMR-A32-68[»]
2FJ5NMR-A32-68[»]
ProteinModelPortalP25713.
SMRP25713. Positions 32-68.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110610. 2 interactions.
IntActP25713. 1 interaction.
MINTMINT-7905812.
STRING9606.ENSP00000200691.

Chemistry

BindingDBP25713.

PTM databases

PhosphoSiteP25713.

Polymorphism databases

DMDM127404.

Proteomic databases

PaxDbP25713.
PRIDEP25713.

Protocols and materials databases

DNASU4504.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000200691; ENSP00000200691; ENSG00000087250.
GeneID4504.
KEGGhsa:4504.
UCSCuc002ejf.3. human.

Organism-specific databases

CTD4504.
GeneCardsGC16P056623.
HGNCHGNC:7408. MT3.
HPACAB017779.
HPA004011.
MIM139255. gene.
neXtProtNX_P25713.
PharmGKBPA31216.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG132957.
HOGENOMHOG000236262.
InParanoidP25713.
KOK14740.
PhylomeDBP25713.

Gene expression databases

ArrayExpressP25713.
BgeeP25713.
CleanExHS_MT3.
GenevestigatorP25713.

Family and domain databases

Gene3D4.10.10.10. 1 hit.
InterProIPR017854. Metalthion_dom.
IPR023587. Metalthion_dom_vert.
IPR003019. Metalthion_sfam_euk.
IPR000006. Metalthion_vert.
IPR018064. Metalthion_vert_metal_BS.
[Graphical view]
PANTHERPTHR23299. PTHR23299. 1 hit.
PfamPF00131. Metallothio. 1 hit.
[Graphical view]
PRINTSPR00860. MTVERTEBRATE.
SUPFAMSSF57868. SSF57868. 1 hit.
PROSITEPS00203. METALLOTHIONEIN_VRT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP25713.
GeneWikiMT3.
GenomeRNAi4504.
NextBio17412.
PROP25713.
SOURCESearch...

Entry information

Entry nameMT3_HUMAN
AccessionPrimary (citable) accession number: P25713
Secondary accession number(s): Q2V574
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: July 9, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Metallothioneins

Classification of metallothioneins and list of entries

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM