Metallothionein-3

Metallothionein-3 (also known as Growth Inhibitory Factor) is a protein that in humans is encoded by the MT3 gene.[3][4][5] It is a 68-amino acid peptide (20 of which are cysteine) that is abnormally under-expressed in the brains of patients suffering from Alzheimer's disease.[6] Metallothionein-3 is a member of the metallothionein family of proteins.

MT3
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 2F5H, 2FJ4, 2FJ5
Identifiers
Aliases	MT3, GIF, GIFB, GRIF, Znmetallothionein 3
External IDs	OMIM: 139255 HomoloGene: 136800 GeneCards: MT3
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q13 Start 56,589,074 bp[1] End 56,591,088 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • zinc ion binding • protein kinase activator activity • metal ion binding • cysteine-type endopeptidase inhibitor activity involved in apoptotic process • antioxidant activity • GO:0001948 protein binding • drug binding • copper ion binding • cadmium ion binding Cellular component • cytoplasm • cytosol • rough endoplasmic reticulum • ribosome • astrocyte end-foot • GO:0097483, GO:0097481 postsynaptic density • synaptic vesicle • cell membrane • dendritic spine • astrocyte projection • intracellular • mitochondrial outer membrane • axon • inclusion body • perinuclear region of cytoplasm • microtubule • extracellular • cell nucleus Biological process • negative regulation of neuron apoptotic process • positive regulation of necrotic cell death • cellular lipid catabolic process • positive regulation of vascular endothelial growth factor receptor signaling pathway • activation of protein kinase B activity • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of protein phosphorylation • positive regulation of cell death • response to hypoxia • zinc ion homeostasis • protein kinase B signaling • histone modification • leptin-mediated signaling pathway • removal of superoxide radicals • astrocyte development • ERK1 and ERK2 cascade • negative regulation of neurogenesis • regulation of response to food • protein stabilization • zinc II ion transport • response to metal ion • negative regulation of apoptotic process • GO:0048554 positive regulation of catalytic activity • cholesterol catabolic process • cellular response to cadmium ion • cellular metal ion homeostasis • cadmium ion homeostasis • response to oxidative stress • negative regulation of hydrogen peroxide catabolic process • negative regulation of cysteine-type endopeptidase activity • positive regulation of transcription, DNA-templated • cellular response to drug • brain development • positive regulation of gene expression • positive regulation of lysosomal membrane permeability • cellular zinc ion homeostasis • negative regulation of cell growth • positive regulation of transcription from RNA polymerase II promoter in response to oxidative stress • negative regulation of oxidoreductase activity • regulation of protein glycosylation • positive regulation of ERK1 and ERK2 cascade • positive regulation of oxygen metabolic process • cellular response to oxidative stress • cellular response to nitric oxide • negative regulation of reactive oxygen species metabolic process • energy reserve metabolic process • cellular proliferation • negative regulation of autophagy • negative regulation of transcription, DNA-templated • negative regulation of axon extension • negative regulation of necrotic cell death • cellular response to hypoxia • negative regulation of neuron death • apoptotic process • detoxification of copper ion • cellular response to copper ion • cellular response to zinc ion • negative regulation of neuron projection development Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4504	n/a
Ensembl	ENSG00000087250	n/a
UniProt	P25713	n/a
RefSeq (mRNA)	NM_005954	n/a
RefSeq (protein)	NP_005945	n/a
Location (UCSC)	Chr 16: 56.59 – 56.59 Mb	n/a
PubMed search	[2]	n/a
Wikidata
View/Edit Human

References

1. GRCh38: Ensembl release 89: ENSG00000087250 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Palmiter RD, Findley SD, Whitmore TE, Durnam DM (Jul 1992). "MT-III, a brain-specific member of the metallothionein gene family". Proceedings of the National Academy of Sciences of the United States of America. 89 (14): 6333–7. doi:10.1073/pnas.89.14.6333. PMC 49495. PMID 1631128.
4. Felizola SJ, Nakamura Y, Arata Y, Ise K, Satoh F, Rainey WE, Midorikawa S, Suzuki S, Sasano H (Sep 2014). "Metallothionein-3 (MT-3) in the human adrenal cortex and its disorders". Endocrine Pathology. 25 (3): 229–235. doi:10.1007/s12022-013-9280-9. PMID 24242700.
5. "Entrez Gene: MT3 metallothionein 3".
6. Uchida, Y; Takio, K; Titani, K; Ihara, Y; Tomonaga, M (August 1991). "The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein". Neuron. 7 (2): 337–347. doi:10.1016/0896-6273(91)90272-2. PMID 1873033.

Further reading

• Aschner M (Aug 1996). "The functional significance of brain metallothioneins". FASEB Journal. 10 (10): 1129–36. doi:10.1096/fasebj.10.10.8751715. PMID 8751715.
• Tsuji S, Kobayashi H, Uchida Y, Ihara Y, Miyatake T (Dec 1992). "Molecular cloning of human growth inhibitory factor cDNA and its down-regulation in Alzheimer's disease". The EMBO Journal. 11 (13): 4843–50. doi:10.1002/j.1460-2075.1992.tb05590.x. PMC 556960. PMID 1464312.
• Hewitt JE, Gordon MM, Taggart RT, Mohandas TK, Alpers DH (Jun 1991). "Human gastric intrinsic factor: characterization of cDNA and genomic clones and localization to human chromosome 11". Genomics. 10 (2): 432–40. doi:10.1016/0888-7543(91)90329-D. PMID 2071148.
• Amoureux MC, Wurch T, Pauwels PJ (Sep 1995). "Modulation of metallothionein-III mRNA content and growth rate of rat C6-glial cells by transfection with human 5-HT1D receptor genes". Biochemical and Biophysical Research Communications. 214 (2): 639–45. doi:10.1006/bbrc.1995.2334. PMID 7677777.
• Naruse S, Igarashi S, Furuya T, Kobayashi H, Miyatake T, Tsuji S (Jul 1994). "Structures of the human and mouse growth inhibitory factor-encoding genes". Gene. 144 (2): 283–7. doi:10.1016/0378-1119(94)90391-3. PMID 8039715.
• Moffatt P, Séguin C (Jun 1998). "Expression of the gene encoding metallothionein-3 in organs of the reproductive system". DNA and Cell Biology. 17 (6): 501–10. doi:10.1089/dna.1998.17.501. PMID 9655243.
• Garrett SH, Sens MA, Shukla D, Nestor S, Somji S, Todd JH, Sens DA (Nov 1999). "Metallothionein isoform 3 expression in the human prostate and cancer-derived cell lines". The Prostate. 41 (3): 196–202. doi:10.1002/(SICI)1097-0045(19991101)41:3<196::AID-PROS7>3.0.CO;2-U. PMID 10517878.
• Ye B, Maret W, Vallee BL (Feb 2001). "Zinc metallothionein imported into liver mitochondria modulates respiration". Proceedings of the National Academy of Sciences of the United States of America. 98 (5): 2317–22. doi:10.1073/pnas.041619198. PMC 30136. PMID 11226237.
• Kim D, Garrett SH, Sens MA, Somji S, Sens DA (Feb 2002). "Metallothionein isoform 3 and proximal tubule vectorial active transport". Kidney International. 61 (2): 464–72. doi:10.1046/j.1523-1755.2002.00153.x. PMID 11849386.
• Palumaa P, Eriste E, Njunkova O, Pokras L, Jörnvall H, Sillard R (May 2002). "Brain-specific metallothionein-3 has higher metal-binding capacity than ubiquitous metallothioneins and binds metals noncooperatively". Biochemistry. 41 (19): 6158–63. doi:10.1021/bi025664v. PMID 11994011.
• Uchida Y, Gomi F, Masumizu T, Miura Y (Aug 2002). "Growth inhibitory factor prevents neurite extension and the death of cortical neurons caused by high oxygen exposure through hydroxyl radical scavenging". The Journal of Biological Chemistry. 277 (35): 32353–9. doi:10.1074/jbc.M111263200. PMID 12058024.
• You HJ, Lee KJ, Jeong HG (Jun 2002). "Overexpression of human metallothionein-III prevents hydrogen peroxide-induced oxidative stress in human fibroblasts". FEBS Letters. 521 (1–3): 175–9. doi:10.1016/S0014-5793(02)02870-3. PMID 12067712.
• Roschitzki B, Vasák M (Jun 2002). "A distinct Cu(4)-thiolate cluster of human metallothionein-3 is located in the N-terminal domain". Journal of Biological Inorganic Chemistry. 7 (6): 611–6. doi:10.1007/s00775-002-0339-1. PMID 12072966.
• Dutta R, Sens DA, Somji S, Sens MA, Garrett SH (Jul 2002). "Metallothionein isoform 3 expression inhibits cell growth and increases drug resistance of PC-3 prostate cancer cells". The Prostate. 52 (2): 89–97. doi:10.1002/pros.10097. PMID 12111700.
• Tate DJ, Miceli MV, Newsome DA (Jan 2002). "Expression of metallothionein isoforms in human chorioretinal complex". Current Eye Research. 24 (1): 12–25. doi:10.1076/ceyr.24.1.12.5426. PMID 12187490.
• You HJ, Oh DH, Choi CY, Lee DG, Hahm KS, Moon AR, Jeong HG (Oct 2002). "Protective effect of metallothionein-III on DNA damage in response to reactive oxygen species". Biochimica et Biophysica Acta (BBA) - General Subjects. 1573 (1): 33–8. doi:10.1016/s0304-4165(02)00325-2. PMID 12383939.