Reviewed, UniProtKB/Swiss-Prot P25713 (MT3_HUMAN)

Names and origin

Protein names

Recommended name:
    Metallothionein-3
      Short name=MT-3
Alternative name(s):
    Metallothionein-III
      Short name=MT-III
    Growth inhibitory factor
    GIFB
      Short name=GIF

Gene names

Name:

MT3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	68 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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
Ligand	Copper Metal-binding Metal-thiolate cluster Zinc
PTM	Acetylation
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell proliferation Ref.1 Traceable author statement. Source: ProtInc cellular metal ion homeostasis Non-traceable author statement. Source: UniProtKB removal of superoxide radicals Inferred from direct assay. Source: UniProtKB response to hypoxia Inferred from direct assay. Source: UniProtKB
Cellular component	synaptic vesicle Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	antioxidant activity Non-traceable author statement. Source: UniProtKB copper ion binding Traceable author statement. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 68

68

Metallothionein-3

Regions

Region

1 – 30

30

Beta

Region

31 – 68

38

Alpha

Sites

Metal binding

6

1

Cluster B By similarity

Metal binding

8

1

Cluster B By similarity

Metal binding

14

1

Cluster B By similarity

Metal binding

16

1

Cluster B By similarity

Metal binding

20

1

Cluster B By similarity

Metal binding

22

1

Cluster B By similarity

Metal binding

25

1

Cluster B By similarity

Metal binding

27

1

Cluster B By similarity

Metal binding

30

1

Cluster B By similarity

Metal binding

34

1

Cluster A By similarity

Metal binding

35

1

Cluster A By similarity

Metal binding

37

1

Cluster A By similarity

Metal binding

38

1

Cluster A By similarity

Metal binding

42

1

Cluster A By similarity

Metal binding

45

1

Cluster A By similarity

Metal binding

49

1

Cluster A By similarity

Metal binding

51

1

Cluster A By similarity

Metal binding

64

1

Cluster A By similarity

Metal binding

66

1

Cluster A By similarity

Metal binding

67

1

Cluster A By similarity

Amino acid modifications

Modified residue

1

1

N-acetylmethionine

Secondary structure

1

.

.

.

.

.

68

Helix Strand Turn

Details...

Beta strand

36 – 38

3

Helix

44 – 47

4

Sequences

	Sequence		Length	Mass (Da)
	P25713-1 [UniParc]. Last modified May 1, 1992. Version 1. Checksum: 59801ECF5BC8A406	FASTA	68	6,927
	10 20 30 40 50 60 MDPETCPCPS GGSCTCADSC KCEGCKCTSC KKSCCSCCPA ECEKCAKDCV CKGGEAAEAE AEKCSCCQ

References

	« Hide 'large scale' referencesShow '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: 1873033] [Abstract] Cited for: NUCLEOTIDE SEQUENCE, PROTEIN SEQUENCE. 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: 1631128] [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: 1464312] [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: 8039715] [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: 7677777] [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, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Shaffer T., Bertucci C., Baier C.N., Rajkumar N., Willa H.T., Daniels M., Downing T.K., Stanaway I.B., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A. 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

B46034.

RefSeq

NP_005945.1.

UniGene

Hs.73133

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2F5H	NMR	-	A	32-68	[»]
2FJ4	NMR	-	A	32-68	[»]
2FJ5	NMR	-	A	32-68	[»]

ModBase

Search...

Polymorphism databases

NIEHS-SNPs

Search...

Genome annotation databases

Ensembl

ENSG00000087250. Homo sapiens. [Contig view]

GeneID

4504.

KEGG

hsa:4504.

Organism-specific databases

H-InvDB

HIX0013054.

HGNC

HGNC:7408. MT3.

HPA

CAB017779.
HPA004011.

MIM

139255. gene.

PharmGKB

PA31216.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P25713.

HOVERGEN

P25713.

Gene expression databases

ArrayExpress

P25713.

CleanEx

HS_MT3.

GermOnline

ENSG00000087250. Homo sapiens.

Family and domain databases

InterPro

IPR015874. 4-disulphide_core.
IPR001450. 4Fe4S_Fe_S_bd.
IPR003019. Metallothionein_sfam_euk.
IPR000006. Metallothionein_vert.
[Graphical view]

Gene3D

G3DSA:4.10.10.10. Metallothionein_vert. 1 hit.

PANTHER

PTHR23299. Metallothionein_vert. 1 hit.

Pfam

PF00131. Metallothio. 1 hit.
[Graphical view]

PRINTS

PR00003. 4DISULPHCORE.
PR00353. 4FE4SFRDOXIN.
PR00860. MTVERTEBRATE.

PROSITE

PS00203. METALLOTHIONEIN_VRT. 1 hit.
[Graphical view]

ProDom

P25713.
[Graphical view] [Entries sharing at least one domain]

BLOCKS

Search...

Other Resources

SOURCE

Search...

ProtoNet

Search...

Entry information

Entry name

MT3_HUMAN

Accession

Primary (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 22, 2008
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)