Metallothionein-3

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

MT3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2F5H, 2FJ4, 2FJ5
Identifiers
Aliases	MT3, GIF, GIFB, GRIF, Znmetallothionein 3
External IDs	OMIM: 139255; MGI: 97173; HomoloGene: 136800; GeneCards: MT3; OMA:MT3 - orthologs
Gene location (Human) Chr. Chromosome 16 (human) Band 16q13 Start 56,589,074 bp End 56,591,088 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8 C5|8 46.29 cM Start 94,879,235 bp End 94,880,774 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nucleus accumbens putamen Brodmann area 9 temporal lobe amygdala substantia nigra caudate nucleus right frontal lobe prefrontal cortex hippocampus proper Top expressed in choroid plexus of fourth ventricle dentate gyrus of hippocampal formation granule cell perirhinal cortex entorhinal cortex CA3 field primary visual cortex superior frontal gyrus dorsomedial hypothalamic nucleus superior colliculus central gray substance of midbrain More reference expression data BioGPS 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 protein binding copper ion binding cadmium ion binding Cellular component cytoplasm cytosol rough endoplasmic reticulum ribosome astrocyte end-foot postsynaptic density synaptic vesicle plasma membrane dendritic spine astrocyte projection intracellular anatomical structure mitochondrial outer membrane axon inclusion body perinuclear region of cytoplasm microtubule extracellular space 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 ion transport response to metal ion negative regulation of apoptotic process 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 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 cell population 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 17751 Ensembl ENSG00000087250 ENSMUSG00000031760 UniProt P25713 P28184 RefSeq (mRNA) NM_005954 NM_013603 RefSeq (protein) NP_005945 NP_038631 Location (UCSC) Chr 16: 56.59 – 56.59 Mb Chr 8: 94.88 – 94.88 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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. S2CID 16464054.
• 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. S2CID 25580202.
• 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. Bibcode:2001PNAS...98.2317Y. 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. S2CID 27345561.
• 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. S2CID 12554119.
• 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. S2CID 25416288.
• 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. S2CID 23835813.
• 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.