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P02795

- MT2_HUMAN

UniProt

P02795 - MT2_HUMAN

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Protein

Metallothionein-2

Gene

MT2A

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

Functioni

Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi5 – 51Divalent metal cation; cluster B1 Publication
Metal bindingi7 – 71Divalent metal cation; cluster B1 Publication
Metal bindingi13 – 131Divalent metal cation; cluster B1 Publication
Metal bindingi15 – 151Divalent metal cation; cluster B1 Publication
Metal bindingi19 – 191Divalent metal cation; cluster B
Metal bindingi21 – 211Divalent metal cation; cluster B
Metal bindingi24 – 241Divalent metal cation; cluster B
Metal bindingi26 – 261Divalent metal cation; cluster B
Metal bindingi29 – 291Divalent metal cation; cluster B
Metal bindingi33 – 331Divalent metal cation; cluster A
Metal bindingi34 – 341Divalent metal cation; cluster A
Metal bindingi36 – 361Divalent metal cation; cluster A
Metal bindingi37 – 371Divalent metal cation; cluster A
Metal bindingi41 – 411Divalent metal cation; cluster A
Metal bindingi44 – 441Divalent metal cation; cluster A
Metal bindingi48 – 481Divalent metal cation; cluster A
Metal bindingi50 – 501Divalent metal cation; cluster A
Metal bindingi57 – 571Divalent metal cation; cluster A
Metal bindingi59 – 591Divalent metal cation; cluster A
Metal bindingi60 – 601Divalent metal cation; cluster A

GO - Molecular functioni

  1. drug binding Source: UniProtKB
  2. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. cellular copper ion homeostasis Source: ProtInc
  2. cellular response to drug Source: UniProtKB
  3. cellular response to erythropoietin Source: UniProtKB
  4. cellular response to interleukin-3 Source: UniProtKB
  5. cellular response to zinc ion Source: UniProtKB
  6. cytokine-mediated signaling pathway Source: Reactome
  7. interferon-gamma-mediated signaling pathway Source: Reactome
  8. negative regulation of growth Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Metal-binding, Metal-thiolate cluster, Zinc

Enzyme and pathway databases

ReactomeiREACT_25078. Interferon gamma signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Metallothionein-2
Short name:
MT-2
Alternative name(s):
Metallothionein-2A
Metallothionein-II
Short name:
MT-II
Gene namesi
Name:MT2A
Synonyms:CES1, MT2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:7406. MT2A.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. nucleus Source: UniProtKB
  4. perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA31214.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 6161Metallothionein-2PRO_0000197245Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine2 Publications

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP02795.
PRIDEiP02795.

PTM databases

PhosphoSiteiP02795.

Expressioni

Gene expression databases

BgeeiP02795.
CleanExiHS_CES1.
HS_MT2A.
ExpressionAtlasiP02795. baseline and differential.
GenevestigatoriP02795.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CXorf40AQ8TE692EBI-996616,EBI-996609
GPR50Q135852EBI-996616,EBI-8550965
PRKD1Q151397EBI-996616,EBI-1181072
SPINK7P580627EBI-996616,EBI-1182445

Protein-protein interaction databases

BioGridi110608. 13 interactions.
DIPiDIP-35232N.
IntActiP02795. 12 interactions.
MINTiMINT-2836376.
STRINGi9606.ENSP00000245185.

Structurei

Secondary structure

1
61
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi7 – 115Combined sources
Helixi27 – 293Combined sources
Beta strandi35 – 373Combined sources
Helixi42 – 443Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1MHUNMR-A31-61[»]
2MHUNMR-A1-30[»]
ProteinModelPortaliP02795.
SMRiP02795. Positions 1-61.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02795.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2929BetaAdd
BLAST
Regioni30 – 6132AlphaAdd
BLAST

Domaini

Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines.

Sequence similaritiesi

Phylogenomic databases

GeneTreeiENSGT00730000110883.
HOGENOMiHOG000236262.
HOVERGENiHBG094456.
InParanoidiP02795.
KOiK14739.
OMAiFLNVFAG.
OrthoDBiEOG7PZS1X.
PhylomeDBiP02795.
TreeFamiTF336054.

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.

P02795-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MDPNCSCAAG DSCTCAGSCK CKECKCTSCK KSCCSCCPVG CAKCAQGCIC
60
KGASDKCSCC A
Length:61
Mass (Da):6,042
Last modified:July 21, 1986 - v1
Checksum:i7B0A7E1F99843078
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti42 – 421A → V.1 Publication
Corresponds to variant rs35109646 [ dbSNP | Ensembl ].
VAR_025840

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J00271 Genomic DNA. Translation: AAA59583.1.
V00594 mRNA. Translation: CAA23841.1.
M26637 mRNA. Translation: AAA59584.1. Sequence problems.
S52379 mRNA. Translation: AAB24908.1.
X97260 mRNA. Translation: CAA65915.1.
BT007315 mRNA. Translation: AAP35979.1.
DQ370420 Genomic DNA. Translation: ABC79300.1.
BC007034 mRNA. Translation: AAH07034.1.
BC070289 mRNA. Translation: AAH70289.1.
CCDSiCCDS10763.1.
PIRiA03271. SMHU2.
I63131.
RefSeqiNP_005944.1. NM_005953.3.
UniGeneiHs.534330.

Genome annotation databases

EnsembliENST00000245185; ENSP00000245185; ENSG00000125148.
GeneIDi4502.
KEGGihsa:4502.
UCSCiuc002ejh.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J00271 Genomic DNA. Translation: AAA59583.1 .
V00594 mRNA. Translation: CAA23841.1 .
M26637 mRNA. Translation: AAA59584.1 . Sequence problems.
S52379 mRNA. Translation: AAB24908.1 .
X97260 mRNA. Translation: CAA65915.1 .
BT007315 mRNA. Translation: AAP35979.1 .
DQ370420 Genomic DNA. Translation: ABC79300.1 .
BC007034 mRNA. Translation: AAH07034.1 .
BC070289 mRNA. Translation: AAH70289.1 .
CCDSi CCDS10763.1.
PIRi A03271. SMHU2.
I63131.
RefSeqi NP_005944.1. NM_005953.3.
UniGenei Hs.534330.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1MHU NMR - A 31-61 [» ]
2MHU NMR - A 1-30 [» ]
ProteinModelPortali P02795.
SMRi P02795. Positions 1-61.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110608. 13 interactions.
DIPi DIP-35232N.
IntActi P02795. 12 interactions.
MINTi MINT-2836376.
STRINGi 9606.ENSP00000245185.

Chemistry

DrugBanki DB00958. Carboplatin.
DB00515. Cisplatin.
DB00526. Oxaliplatin.

PTM databases

PhosphoSitei P02795.

Proteomic databases

MaxQBi P02795.
PRIDEi P02795.

Protocols and materials databases

DNASUi 4502.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000245185 ; ENSP00000245185 ; ENSG00000125148 .
GeneIDi 4502.
KEGGi hsa:4502.
UCSCi uc002ejh.3. human.

Organism-specific databases

CTDi 4502.
GeneCardsi GC16P056642.
HGNCi HGNC:7406. MT2A.
MIMi 156360. gene.
neXtProti NX_P02795.
PharmGKBi PA31214.
GenAtlasi Search...

Phylogenomic databases

GeneTreei ENSGT00730000110883.
HOGENOMi HOG000236262.
HOVERGENi HBG094456.
InParanoidi P02795.
KOi K14739.
OMAi FLNVFAG.
OrthoDBi EOG7PZS1X.
PhylomeDBi P02795.
TreeFami TF336054.

Enzyme and pathway databases

Reactomei REACT_25078. Interferon gamma signaling.

Miscellaneous databases

ChiTaRSi MT2A. human.
EvolutionaryTracei P02795.
GeneWikii Metallothionein_2A.
GenomeRNAii 4502.
NextBioi 17406.
PROi P02795.
SOURCEi Search...

Gene expression databases

Bgeei P02795.
CleanExi HS_CES1.
HS_MT2A.
ExpressionAtlasi P02795. baseline and differential.
Genevestigatori P02795.

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. "Primary structure of human hepatic metallothionein."
    Kissling M.M., Kaegi J.H.R.
    FEBS Lett. 82:247-250(1977) [PubMed] [Europe PMC] [Abstract]
    Cited for: PRELIMINARY PROTEIN SEQUENCE.
    Tissue: Liver.
  2. "Human metallothionein genes -- primary structure of the metallothionein-II gene and a related processed gene."
    Karin M., Richards R.I.
    Nature 299:797-802(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Human metallothionein genes: molecular cloning and sequence analysis of the mRNA."
    Karin M., Richards R.I.
    Nucleic Acids Res. 10:3165-3173(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Changes in brain gene expression shared by scrapie and Alzheimer disease."
    Duguid J.R., Bohmont C.W., Liu N.G., Tourtellotte W.W.
    Proc. Natl. Acad. Sci. U.S.A. 86:7260-7264(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. "Expression of human metallothionein-II fusion protein in Escherichia coli."
    Yamazaki S., Nakanishi M., Hamamoto T., Hirata H., Ebihara A., Tokue A., Kagawa Y.
    Biochem. Int. 28:451-460(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  6. "Cloning and sequencing a novel metallothionein 1 isoform expressed in human reticulocytes."
    Lambert E., Kille P., Kay J., Swaminathan R.
    Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  7. "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].
  8. NIEHS SNPs program
    Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-42.
  9. "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 and Kidney.
  10. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. "Three-dimensional structure of human [113Cd7]metallothionein-2 in solution determined by nuclear magnetic resonance spectroscopy."
    Messerle B.A., Schaeffer A., Vasak M., Kaegi J.H.R., Wuethrich K.
    J. Mol. Biol. 214:765-779(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.
  12. "Comparison of the solution conformations of human [Zn7]-metallothionein-2 and [Cd7]-metallothionein-2 using nuclear magnetic resonance spectroscopy."
    Messerle B.A., Schaeffer A., Vasak M., Kaegi J.H.R., Wuethrich K.
    J. Mol. Biol. 225:433-443(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR.

Entry informationi

Entry nameiMT2_HUMAN
AccessioniPrimary (citable) accession number: P02795
Secondary accession number(s): Q14823, Q2HXR9, Q53XT9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 26, 2014
This is version 156 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

Miscellaneous

This metallothionein binds zinc.

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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. Metallothioneins
    Classification of metallothioneins and list of entries
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3