P02795 (MT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metallothionein-2
Short name=MT-2

Alternative name(s):
Metallothionein-2A
Metallothionein-II
Short name=MT-II

Gene names

Name:	MT2A
Synonyms:	CES1, MT2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	61 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Domain	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.
Miscellaneous	This metallothionein binds zinc.
Sequence similarities	Belongs to the metallothionein superfamily. Type 1 family.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	Metal-binding Metal-thiolate cluster Zinc
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular copper ion homeostasis Traceable author statement PubMed 6719135. Source: ProtInc cellular response to drug Inferred from direct assay PubMed 19536566. Source: UniProtKB cellular response to erythropoietin Inferred from expression pattern PubMed 11168427. Source: UniProtKB cellular response to interleukin-3 Inferred from expression pattern PubMed 11168427. Source: UniProtKB cellular response to zinc ion Inferred from expression pattern PubMed 11168427. Source: UniProtKB interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome negative regulation of growth Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	drug binding Inferred from direct assay PubMed 19536566. Source: UniProtKB zinc ion binding Inferred from direct assay PubMed 19536566. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CXorf40A	Q8TE69	2	EBI-996616,EBI-996609
PRKD1	Q15139	7	EBI-996616,EBI-1181072
SPINK7	P58062	7	EBI-996616,EBI-1182445

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 61

61

Metallothionein-2

PRO_0000197245

Regions

Region

1 – 29

29

Beta

Region

30 – 61

32

Alpha

Sites

Metal binding

5

1

Divalent metal cation; cluster B Ref.10

Metal binding

7

1

Divalent metal cation; cluster B Ref.10

Metal binding

13

1

Divalent metal cation; cluster B Ref.10

Metal binding

15

1

Divalent metal cation; cluster B Ref.10

Metal binding

19

1

Divalent metal cation; cluster B

Metal binding

21

1

Divalent metal cation; cluster B

Metal binding

24

1

Divalent metal cation; cluster B

Metal binding

26

1

Divalent metal cation; cluster B

Metal binding

29

1

Divalent metal cation; cluster B

Metal binding

33

1

Divalent metal cation; cluster A

Metal binding

34

1

Divalent metal cation; cluster A

Metal binding

36

1

Divalent metal cation; cluster A

Metal binding

37

1

Divalent metal cation; cluster A

Metal binding

41

1

Divalent metal cation; cluster A

Metal binding

44

1

Divalent metal cation; cluster A

Metal binding

48

1

Divalent metal cation; cluster A

Metal binding

50

1

Divalent metal cation; cluster A

Metal binding

57

1

Divalent metal cation; cluster A

Metal binding

59

1

Divalent metal cation; cluster A

Metal binding

60

1

Divalent metal cation; cluster A

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Natural variations

Natural variant

42

1

A → V. Ref.8
Corresponds to variant rs35109646 [ dbSNP | Ensembl ].

VAR_025840

Secondary structure

1

.

.

.

.

.

.

.

.

.

61

Helix Strand Turn

Details...

Beta strand

7 – 11

5

Helix

27 – 29

3

Beta strand

35 – 37

3

Helix

42 – 44

3

Sequences

	Sequence		Length	Mass (Da)
	P02795 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 7B0A7E1F99843078	FASTA	61	6,042
	10 20 30 40 50 60 MDPNCSCAAG DSCTCAGSCK CKECKCTSCK KSCCSCCPVG CAKCAQGCIC KGASDKCSCC A

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"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.
[11]	"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.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00022498.

PIR

SMHU2. A03271.
I63131.

RefSeq

NP_005944.1. NM_005953.3.

UniGene

Hs.647371.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MHU	NMR	-	A	31-61	[»]
2MHU	NMR	-	A	1-30	[»]

ProteinModelPortal

P02795.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35232N.

IntAct

P02795. 7 interactions.

MINT

MINT-2836376.

STRING

9606.ENSP00000245185.

PTM databases

PhosphoSite

P02795.

Polymorphism databases

DMDM

127397.

Proteomic databases

PRIDE

P02795.

Protocols and materials databases

DNASU

4502.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000245185; ENSP00000245185; ENSG00000125148.

GeneID

4502.

KEGG

hsa:4502.

UCSC

uc002ejh.3. human.

Organism-specific databases

CTD

4502.

GeneCards

GC16P056642.

HGNC

HGNC:7406. MT2A.

MIM

156360. gene.

neXtProt

NX_P02795.

PharmGKB

PA31214.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000236262.

HOVERGEN

HBG094456.

InParanoid

P02795.

KO

K14739.

OMA

CICKAAS.

OrthoDB

EOG46WZB6.

PhylomeDB

P02795.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P02795.

Bgee

P02795.

CleanEx

HS_CES1.
HS_MT2A.

Genevestigator

P02795.

GermOnline

ENSG00000125148. Homo sapiens.

Family and domain databases

Gene3D

4.10.10.10. 1 hit.

InterPro

IPR017854. Metalthion_dom.
IPR023587. Metalthion_dom_vert.
IPR003019. Metalthion_sfam_euk.
IPR000006. Metalthion_vert.
IPR018064. Metalthion_vert_metal_BS.
[Graphical view]

PANTHER

PTHR23299. PTHR23299. 1 hit.

Pfam

PF00131. Metallothio. 1 hit.
[Graphical view]

PRINTS

PR00860. MTVERTEBRATE.

SUPFAM

SSF57868. Metallothionein_sfam. 1 hit.

PROSITE

PS00203. METALLOTHIONEIN_VRT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

MT2A. human.

EvolutionaryTrace

P02795.

GenomeRNAi

4502.

NextBio

17406.

SOURCE

Search...

Entry information

Entry name

MT2_HUMAN

Accession

Primary (citable) accession number: P02795
Secondary accession number(s): Q14823, Q2HXR9, Q53XT9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 1, 2013
This is version 142 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.