P25713 (MT3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

MT3

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	68 AA.
Sequence status	Complete.
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 Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	ERK1 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 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 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 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-dependent 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 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 transcription from RNA polymerase II promoter in response to oxidative stress Inferred from direct assay PubMed 18554677. 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 cascade 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 zinc ion transport Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	inclusion body Inferred from direct assay PubMed 20039155. 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_function	antioxidant 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 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...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 68

68

Metallothionein-3

PRO_0000197250

Regions

Region

1 – 30

30

Beta

Region

31 – 68

38

Alpha

Sites

Metal binding

6

1

Divalent metal cation; cluster B By similarity

Metal binding

8

1

Divalent metal cation; cluster B By similarity

Metal binding

14

1

Divalent metal cation; cluster B By similarity

Metal binding

16

1

Divalent metal cation; cluster B By similarity

Metal binding

20

1

Divalent metal cation; cluster B By similarity

Metal binding

22

1

Divalent metal cation; cluster B By similarity

Metal binding

25

1

Divalent metal cation; cluster B By similarity

Metal binding

27

1

Divalent metal cation; cluster B By similarity

Metal binding

30

1

Divalent metal cation; cluster B By similarity

Metal binding

34

1

Divalent metal cation; cluster A By similarity

Metal binding

35

1

Divalent metal cation; cluster A By similarity

Metal binding

37

1

Divalent metal cation; cluster A By similarity

Metal binding

38

1

Divalent metal cation; cluster A By similarity

Metal binding

42

1

Divalent metal cation; cluster A By similarity

Metal binding

45

1

Divalent metal cation; cluster A By similarity

Metal binding

49

1

Divalent metal cation; cluster A By similarity

Metal binding

51

1

Divalent metal cation; cluster A By similarity

Metal binding

64

1

Divalent metal cation; cluster A By similarity

Metal binding

66

1

Divalent metal cation; cluster A By similarity

Metal binding

67

1

Divalent metal cation; 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

Helix

50 – 53

4

Turn

55 – 59

5

Beta strand

60 – 62

3

Turn

65 – 67

3

Sequences

	Sequence		Length	Mass (Da)
	P25713 [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] [Europe PMC] [Abstract] Cited for: 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] [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

NIEHS-SNPs

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.

IPI

IPI00016666.

PIR

B46034.

RefSeq

NP_005945.1. NM_005954.2.

UniGene

Hs.73133.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P25713.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000200691.

PTM databases

PhosphoSite

P25713.

Polymorphism databases

DMDM

127404.

Proteomic databases

PaxDb

P25713.

PRIDE

P25713.

Protocols and materials databases

DNASU

4504.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000200691; ENSP00000200691; ENSG00000087250.

GeneID

4504.

KEGG

hsa:4504.

UCSC

uc002ejf.3. human.

Organism-specific databases

CTD

4504.

GeneCards

GC16P056623.

HGNC

HGNC:7408. MT3.

HPA

CAB017779.
HPA004011.

MIM

139255. gene.

neXtProt

NX_P25713.

PharmGKB

PA31216.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG132957.

HOGENOM

HOG000236262.

InParanoid

P25713.

KO

K14740.

OMA

ETCPCPT.

OrthoDB

EOG408N9W.

Gene expression databases

ArrayExpress

P25713.

Bgee

P25713.

CleanEx

HS_MT3.

Genevestigator

P25713.

GermOnline

ENSG00000087250. 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

BindingDB

P25713.

ChEMBL

CHEMBL1250357.

EvolutionaryTrace

P25713.

GenomeRNAi

4504.

NextBio

17412.

SOURCE

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:	May 1, 2013
This is version 127 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.