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P25713

- MT3_HUMAN

UniProt

P25713 - MT3_HUMAN

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Protein
Metallothionein-3
Gene
MT3
Organism
Homo sapiens (Human)
Status
Reviewed - 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 B By similarity
Metal bindingi8 – 81Divalent metal cation; cluster B By similarity
Metal bindingi14 – 141Divalent metal cation; cluster B By similarity
Metal bindingi16 – 161Divalent metal cation; cluster B By similarity
Metal bindingi20 – 201Divalent metal cation; cluster B By similarity
Metal bindingi22 – 221Divalent metal cation; cluster B By similarity
Metal bindingi25 – 251Divalent metal cation; cluster B By similarity
Metal bindingi27 – 271Divalent metal cation; cluster B By similarity
Metal bindingi30 – 301Divalent metal cation; cluster B By similarity
Metal bindingi34 – 341Divalent metal cation; cluster A By similarity
Metal bindingi35 – 351Divalent metal cation; cluster A By similarity
Metal bindingi37 – 371Divalent metal cation; cluster A By similarity
Metal bindingi38 – 381Divalent metal cation; cluster A By similarity
Metal bindingi42 – 421Divalent metal cation; cluster A By similarity
Metal bindingi45 – 451Divalent metal cation; cluster A By similarity
Metal bindingi49 – 491Divalent metal cation; cluster A By similarity
Metal bindingi51 – 511Divalent metal cation; cluster A By similarity
Metal bindingi64 – 641Divalent metal cation; cluster A By similarity
Metal bindingi66 – 661Divalent metal cation; cluster A By similarity
Metal bindingi67 – 671Divalent metal cation; cluster A By 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
Complete GO annotation...

GO - Biological processi

  1. ERK1 and ERK2 cascade Source: UniProtKB
  2. activation of protein kinase B activity Source: UniProtKB
  3. astrocyte development Source: UniProtKB
  4. cadmium ion homeostasis Source: UniProtKB
  5. cell proliferation Source: ProtInc
  6. cellular lipid catabolic process Source: UniProtKB
  7. cellular metal ion homeostasis Source: UniProtKB
  8. cellular response to cadmium ion Source: UniProtKB
  9. cellular response to drug Source: UniProtKB
  10. cellular response to hypoxia Source: UniProtKB
  11. cellular response to nitric oxide Source: UniProtKB
  12. cellular response to oxidative stress Source: UniProtKB
  13. cellular zinc ion homeostasis Source: UniProtKB
  14. cholesterol catabolic process Source: UniProtKB
  15. energy reserve metabolic process 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 ERK1 and ERK2 cascade Source: UniProtKB
  30. positive regulation of catalytic activity Source: UniProtKB
  31. positive regulation of cell death 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 from RNA polymerase II promoter in response to oxidative stress Source: UniProtKB
  38. positive regulation of transcription, DNA-templated 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
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: 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
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31216.

PTM / Processingi

Molecule processing

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

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.

Miscellaneous databases

EvolutionaryTraceiP25713.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 3030Beta
Add
BLAST
Regioni31 – 6838Alpha
Add
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...

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

« 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: July 9, 2014
This is version 138 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