MT3 (metallothionein 3)

Gene

• Entrez ID: 4504
• Gene name: Metallothionein 3
• Gene symbol: MT3
• Synonyms (NCBI Gene): GIF, GIFB, GRIF, ZnMT3
• Chromosome: 16
• Chromosome location: 16q13
• Summary: This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions. This gene family member displays tissue-specific

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT2046464	hsa-miR-3974	CLIP-seq
MIRT2046465	hsa-miR-4691-5p	CLIP-seq
MIRT2046466	hsa-miR-616	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001666	Process	Response to hypoxia	IDA	12763630
GO:0001934	Process	Positive regulation of protein phosphorylation	IDA	18295594
GO:0005507	Function	Copper ion binding	IDA	21320589
GO:0005507	Function	Copper ion binding	IEA
GO:0005507	Function	Copper ion binding	TAS	8751715
GO:0005515	Function	Protein binding	IPI	20646067, 21044950, 21320589
GO:0005615	Component	Extracellular space	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	10355541
GO:0005741	Component	Mitochondrial outer membrane	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005840	Component	Ribosome	IEA
GO:0005874	Component	Microtubule	IEA
GO:0006112	Process	Energy reserve metabolic process	IEA
GO:0006112	Process	Energy reserve metabolic process	ISS
GO:0006829	Process	Zinc ion transport	IEA
GO:0006829	Process	Zinc ion transport	ISS
GO:0006882	Process	Intracellular zinc ion homeostasis	IBA
GO:0006882	Process	Intracellular zinc ion homeostasis	IEA
GO:0006882	Process	Intracellular zinc ion homeostasis	ISS
GO:0006979	Process	Response to oxidative stress	IEA
GO:0008021	Component	Synaptic vesicle	IEA
GO:0008021	Component	Synaptic vesicle	ISS
GO:0008270	Function	Zinc ion binding	IDA	17712581, 21320589
GO:0008270	Function	Zinc ion binding	IEA
GO:0010273	Process	Detoxification of copper ion	IBA
GO:0010628	Process	Positive regulation of gene expression	IDA	18295594
GO:0010977	Process	Negative regulation of neuron projection development	TAS	1873033
GO:0016209	Function	Antioxidant activity	NAS	12383939
GO:0016234	Component	Inclusion body	IDA	20039155
GO:0019430	Process	Removal of superoxide radicals	IDA	12383939
GO:0030003	Process	Intracellular monoatomic cation homeostasis	IEA
GO:0030003	Process	Intracellular monoatomic cation homeostasis	NAS	12383939
GO:0030003	Process	Intracellular monoatomic cation homeostasis	TAS	21818286
GO:0030295	Function	Protein kinase activator activity	IDA	18295594
GO:0030308	Process	Negative regulation of cell growth	IDA	16601975, 17712581
GO:0030308	Process	Negative regulation of cell growth	IMP	16945328
GO:0030424	Component	Axon	IEA
GO:0030517	Process	Negative regulation of axon extension	IDA	16601975, 17712581
GO:0030949	Process	Positive regulation of vascular endothelial growth factor receptor signaling pathway	IDA	18295594
GO:0032095	Process	Regulation of response to food	IEA
GO:0032095	Process	Regulation of response to food	ISS
GO:0032148	Process	Activation of protein kinase B activity	IDA	18295594
GO:0033210	Process	Leptin-mediated signaling pathway	IEA
GO:0033210	Process	Leptin-mediated signaling pathway	ISS
GO:0034599	Process	Cellular response to oxidative stress	IEP	20039155
GO:0034614	Process	Cellular response to reactive oxygen species	IDA	18554677
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043197	Component	Dendritic spine	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	IEA
GO:0043524	Process	Negative regulation of neuron apoptotic process	ISS
GO:0045893	Process	Positive regulation of DNA-templated transcription	IDA	18295594
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	ISS
GO:0046870	Function	Cadmium ion binding	IDA	16601975, 17712581, 18157556
GO:0046872	Function	Metal ion binding	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IDA	20039155
GO:0050768	Process	Negative regulation of neurogenesis	IEA
GO:0050821	Process	Protein stabilization	IDA	18295594
GO:0051354	Process	Negative regulation of oxidoreductase activity	IDA	21320589
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IBA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IDA	18295594
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IEA
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	ISS
GO:0071276	Process	Cellular response to cadmium ion	IBA
GO:0071280	Process	Cellular response to copper ion	IBA
GO:0071294	Process	Cellular response to zinc ion	IBA
GO:0071456	Process	Cellular response to hypoxia	IEP	18206644
GO:0071585	Process	Detoxification of cadmium ion	IEA
GO:0097449	Component	Astrocyte projection	IEA
GO:0097450	Component	Astrocyte end-foot	IEA
GO:0140487	Function	Metal ion sequestering activity	IEA
GO:1990748	Process	Cellular detoxification	IDA	18554677
GO:2000296	Process	Negative regulation of hydrogen peroxide catabolic process	IEA
GO:2000376	Process	Positive regulation of oxygen metabolic process	IEA
GO:2000376	Process	Positive regulation of oxygen metabolic process	ISS

Other IDs

• MIM: 139255
• HGNC: 7408
• e!Ensembl: ENSG00000087250

Protein

• UniProt ID: P25713
• Protein name: Metallothionein-3 (MT-3) (GIFB) (GIF) (Growth inhibitory factor) (Metallothionein-III) (MT-III)
• Protein 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.
• PDB: 2F5H, 2FJ4, 2FJ5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00131	Metallothio	1 → 68	Metallothionein	Domain

• Tissue specificity: TISSUE SPECIFICITY: Abundant in a subset of astrocytes in the normal human brain, but greatly reduced in the Alzheimer disease (AD) brain.
• Sequence:

  MDPETCPCPSGGSCTCADSCKCEGCKCTSCKKSCCSCCPAECEKCAKDCVCKGGEAAEAE
  AEKCSCCQ

• Sequence length: 68

Pathways

Reactome:

Metallothioneins bind metals

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMERS DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, NON-SMALL-CELL LUNG	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EOSINOPHILIC ESOPHAGITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEIZURES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
URINARY BLADDER NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	21818286		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	16601360, 24242700		★☆☆☆☆ Found in Text Mining only
Adrenocortical carcinoma	Adrenocortical carcinoma	BEFREE	24242700		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	1464312, 17389590, 39993744	Inhibit	★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	30357199		★☆☆☆☆ Found in Text Mining only
Amyotrophic lateral sclerosis 1	Amyotrophic lateral sclerosis	Pubtator	12417341	Associate	★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	22722772		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	22722772		★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	Pubtator	30932010	Stimulate	★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	16428254		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	29524106		★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	16854967, 30813460		★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	CTD_human_DG	16854967		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	CTD_human_DG	21170156		★☆☆☆☆ Found in Text Mining only
Breast Diseases	Breast Diseases	BEFREE	27840910		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	11438449	Stimulate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	25015776, 28545470, 37643511	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinogenesis	Carcinogenesis	Pubtator	30813460	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Basal Cell	Basal cell carcinoma	Pubtator	23042264, 25290577	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Basal Cell	Basal cell carcinoma	Pubtator	25015776	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	27965980, 36133439, 38097352	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma in Situ	Carcinoma in situ	Pubtator	10811567	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Intraductal Noninfiltrating	Intraductal noninfiltrating carcinoma	Pubtator	11438449	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	16854967, 30813460		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	27602766		★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	25015776, 25290577	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	27840910		★☆☆☆☆ Found in Text Mining only
Childhood Acute Myeloid Leukemia	Acute Myeloid Leukemia	BEFREE	24962166		★☆☆☆☆ Found in Text Mining only
Clonic Seizures	Clonic Seizures	CTD_human_DG	23266720		★☆☆☆☆ Found in Text Mining only
Complex partial seizures	Seizure	CTD_human_DG	23266720		★☆☆☆☆ Found in Text Mining only
Conn Adenoma	Conn Adenoma	BEFREE	24242700		★☆☆☆☆ Found in Text Mining only
Conn Syndrome	Conn Syndrome	BEFREE	24242700		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	12391607		★☆☆☆☆ Found in Text Mining only
Depressive Disorder	Major depressive disorder	Pubtator	31321953	Stimulate	★☆☆☆☆ Found in Text Mining only
Epilepsy Temporal Lobe	Temporal lobe epilepsy	Pubtator	23028585, 31321953	Associate	★☆☆☆☆ Found in Text Mining only
Epileptic drop attack	Hypotonic seizures	CTD_human_DG	23266720		★☆☆☆☆ Found in Text Mining only
Esophageal carcinoma	Esophageal Carcinoma	BEFREE	24222235		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophagus Neoplasm	BEFREE	24222235		★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	16351731	Inhibit	★☆☆☆☆ Found in Text Mining only
Gastrointestinal Stromal Tumors	Gastrointestinal stromal tumor	Pubtator	23986211	Associate	★☆☆☆☆ Found in Text Mining only
Generalized seizures	Seizure	CTD_human_DG	23266720		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	30932010		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	30932010	Stimulate	★☆☆☆☆ Found in Text Mining only
Glycogen Storage Disease Type IV	Glycogen storage disease	Pubtator	30932010	Stimulate	★☆☆☆☆ Found in Text Mining only
Grade I Astrocytoma	Grade I Astrocytoma	BEFREE	30932010		★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	30813460	Stimulate	★☆☆☆☆ Found in Text Mining only
Intestinal Diseases	Intestinal Diseases	BEFREE	29141526		★☆☆☆☆ Found in Text Mining only
Intrinsic Factor Deficiency	Intrinsic Factor Deficiency	BEFREE	22929189, 23402911		★☆☆☆☆ Found in Text Mining only
Jacksonian Seizure	Jacksonian Seizure	CTD_human_DG	23266720		★☆☆☆☆ Found in Text Mining only
Kaposi Sarcoma	Kaposi Sarcoma	BEFREE	12476040		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	34437439	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	24962166	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	24962166	Inhibit	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	24962166		★☆☆☆☆ Found in Text Mining only
Lupus Nephritis	Lupus nephritis	Pubtator	18601746	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	CTD_human_DG	21170156		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	28545470		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of esophagus	Esophagus Neoplasm	BEFREE	24222235		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	27602766		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	16854967, 30813460		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	CTD_human_DG	16854967		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	9295238		★☆☆☆☆ Found in Text Mining only
Mammary Carcinoma, Human	Marfan Syndrome	CTD_human_DG	21170156		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	CTD_human_DG	21170156		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms, Human	Mammary Neoplasms	CTD_human_DG	21170156		★☆☆☆☆ Found in Text Mining only
Megaloblastic Anemia 1	Anemia	BEFREE	22929189		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	19383853, 25290577	Associate	★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	12391607		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	24252376	Associate	★☆☆☆☆ Found in Text Mining only
Motor Neuron Disease	Motor Neuron Disease	BEFREE	14625437		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	10537155, 16351731, 23482768, 24242700, 24962166, 8396466		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	29435113		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	39993744	Inhibit	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	29085556		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	CTD_human_DG	17043644		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	23482768		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	31799835		★☆☆☆☆ Found in Text Mining only
Polycythemia	Polycythemia	BEFREE	26485402		★☆☆☆☆ Found in Text Mining only
Prostatic Hyperplasia	Prostatic Hyperplasia	LHGDN	18208603		★☆☆☆☆ Found in Text Mining only
Prostatic Hyperplasia	Prostatic hyperplasia	Pubtator	18208603	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	LHGDN	12111700		★☆☆☆☆ Found in Text Mining only
Psychotic Disorders	Psychotic disorders	Pubtator	18992145	Associate	★☆☆☆☆ Found in Text Mining only
Respiratory Distress Syndrome, Adult	Respiratory Distress Syndrome	CTD_human_DG	25070658		★☆☆☆☆ Found in Text Mining only
Respiratory Distress Syndrome, Adult	Respiratory Distress Syndrome	BEFREE	29965781		★☆☆☆☆ Found in Text Mining only
Scleroderma	Scleroderma	BEFREE	9073533		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	23028585	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Senile Plaques	Senile Plaques	BEFREE	22722772		★☆☆☆☆ Found in Text Mining only
Single Seizure	Seizure	CTD_human_DG	23266720		★☆☆☆☆ Found in Text Mining only
Skin Diseases	Skin disease	Pubtator	25290577	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	LHGDN	16351731		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	16351731		★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	12538345		★☆☆☆☆ Found in Text Mining only
Systemic Scleroderma	Scleroderma	BEFREE	9073533		★☆☆☆☆ Found in Text Mining only
Tonic - clonic seizures	Seizure	CTD_human_DG	23266720		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Diseases	Urinary Bladder Diseases	BEFREE	10811567		★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	10811567, 30813460, 32512576	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Visual seizure	Seizure	CTD_human_DG	23266720		★☆☆☆☆ Found in Text Mining only