This gene encodes a subunit of the TIM23 inner mitochondrial membrane translocase complex. The encoded protein functions as the receptor subunit that recognizes the mitochondrial targeting signal, or presequence, on protein cargo that is destined for the mitochondrial inner membrane and matrix. This protein may also play a role in maintaining the membrane permeability barrier, ... See more...

Aliases for TIMM50 Gene

Aliases for TIMM50 Gene

  • Translocase Of Inner Mitochondrial Membrane 50 2 3 5
  • Mitochondrial Import Inner Membrane Translocase Subunit TIM50 3 4
  • TIM50 3 4
  • Translocase Of Inner Mitochondrial Membrane 50 Homolog (Yeast) 2
  • Homolog Of Yeast Tim50 3
  • Tim50-Like Protein 3
  • TIM50L 3
  • MGCA9 3

External Ids for TIMM50 Gene

Previous GeneCards Identifiers for TIMM50 Gene

  • GC19P044662
  • GC19P044663
  • GC19P039971
  • GC19P036417

Summaries for TIMM50 Gene

Entrez Gene Summary for TIMM50 Gene

  • This gene encodes a subunit of the TIM23 inner mitochondrial membrane translocase complex. The encoded protein functions as the receptor subunit that recognizes the mitochondrial targeting signal, or presequence, on protein cargo that is destined for the mitochondrial inner membrane and matrix. This protein may also play a role in maintaining the membrane permeability barrier, and knockdown of this gene in human cells results in the release of cytochrome c and apoptosis. [provided by RefSeq, Jul 2016]

GeneCards Summary for TIMM50 Gene

TIMM50 (Translocase Of Inner Mitochondrial Membrane 50) is a Protein Coding gene. Diseases associated with TIMM50 include 3-Methylglutaconic Aciduria, Type Ix and 3-Methylglutaconic Aciduria. Among its related pathways are Mitochondrial protein import and Metabolism of proteins. Gene Ontology (GO) annotations related to this gene include RNA binding and phosphoprotein phosphatase activity. An important paralog of this gene is CTDSPL2.

UniProtKB/Swiss-Prot Summary for TIMM50 Gene

  • Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Has some phosphatase activity in vitro; however such activity may not be relevant in vivo.
  • [Isoform 2]: May participate in the release of snRNPs and SMN from the Cajal body.

Gene Wiki entry for TIMM50 Gene

Additional gene information for TIMM50 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TIMM50 Gene

Genomics for TIMM50 Gene

GeneHancer (GH) Regulatory Elements for TIMM50 Gene

Promoters and enhancers for TIMM50 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TIMM50 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TIMM50

Top Transcription factor binding sites by QIAGEN in the TIMM50 gene promoter:
  • AML1a
  • AREB6
  • C/EBPalpha
  • HOXA5
  • Max1
  • MAZR
  • RORalpha1
  • RORalpha2
  • Zic3

Genomic Locations for TIMM50 Gene

Genomic Locations for TIMM50 Gene
chr19:39,480,412-39,493,785
(GRCh38/hg38)
Size:
13,374 bases
Orientation:
Plus strand
chr19:39,971,052-39,984,422
(GRCh37/hg19)
Size:
13,371 bases
Orientation:
Plus strand

Genomic View for TIMM50 Gene

Genes around TIMM50 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIMM50 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIMM50 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TIMM50 Gene

Proteins for TIMM50 Gene

  • Protein details for TIMM50 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q3ZCQ8-TIM50_HUMAN
    Recommended name:
    Mitochondrial import inner membrane translocase subunit TIM50
    Protein Accession:
    Q3ZCQ8
    Secondary Accessions:
    • Q330K1
    • Q6QA00
    • Q96FJ5
    • Q96GY2
    • Q9H370

    Protein attributes for TIMM50 Gene

    Size:
    353 amino acids
    Molecular mass:
    39646 Da
    Quaternary structure:
    • Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50; within this complex, directly interacts with TIMM23 (PubMed:15044455). The complex interacts with the TIMM44 component of the PAM complex and with DNAJC15 (PubMed:23263864). Isoform 2: Interacts with COIL and snRNPs (PubMed:16008839).
    SequenceCaution:
    • Sequence=AAG35534.1; Type=Miscellaneous discrepancy; Note=Chimera.; Evidence={ECO:0000305};

    Alternative splice isoforms for TIMM50 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TIMM50 Gene

Post-translational modifications for TIMM50 Gene

  • Ubiquitination at Lys232, Lys312, and Lys334
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for TIMM50 Gene

Domains & Families for TIMM50 Gene

Gene Families for TIMM50 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for TIMM50 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TIMM50 Gene

GenScript: Design optimal peptide antigens:
  • Translocase of inner mitochondrial membrane 50 homolog (S. cerevisiae) (Q0VAB1_HUMAN)
  • Mitochondrial import inner membrane translocase subunit TIM50 (TIM50_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q3ZCQ8

UniProtKB/Swiss-Prot:

TIM50_HUMAN :
  • The FCP1 homology domain does not contain the canonical D-x-D-x-[TV] active site, suggesting that it probably does not display phosphatase activity in vivo.
  • Belongs to the TIM50 family.
Domain:
  • The FCP1 homology domain does not contain the canonical D-x-D-x-[TV] active site, suggesting that it probably does not display phosphatase activity in vivo.
Family:
  • Belongs to the TIM50 family.
genes like me logo Genes that share domains with TIMM50: view

Function for TIMM50 Gene

Molecular function for TIMM50 Gene

UniProtKB/Swiss-Prot Function:
Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. Has some phosphatase activity in vitro; however such activity may not be relevant in vivo.
UniProtKB/Swiss-Prot Function:
[Isoform 2]: May participate in the release of snRNPs and SMN from the Cajal body.

Gene Ontology (GO) - Molecular Function for TIMM50 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003723 RNA binding IEA --
GO:0004721 phosphoprotein phosphatase activity IDA 15044455
GO:0004722 protein serine/threonine phosphatase activity IDA 15044455
GO:0004725 protein tyrosine phosphatase activity IDA 15044455
GO:0005134 interleukin-2 receptor binding IDA 15044455
genes like me logo Genes that share ontologies with TIMM50: view
genes like me logo Genes that share phenotypes with TIMM50: view

Human Phenotype Ontology for TIMM50 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TIMM50 Gene

MGI Knock Outs for TIMM50:
  • Timm50 Timm50<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for TIMM50 Gene

miRTarBase miRNAs that target TIMM50

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIMM50

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for TIMM50 Gene

Localization for TIMM50 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIMM50 Gene

Mitochondrion inner membrane; Single-pass membrane protein.
[Isoform 2]: Nucleus speckle. Note=Nuclear and enriched in speckles with snRNPs. {ECO:0000269 PubMed:16008839}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TIMM50 gene
Compartment Confidence
mitochondrion 5
nucleus 5
peroxisome 2
endoplasmic reticulum 2
cytosol 2
plasma membrane 1
cytoskeleton 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TIMM50 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005739 mitochondrion IDA,IEA --
GO:0005743 mitochondrial inner membrane IDA,IEA 15044455
GO:0005744 TIM23 mitochondrial import inner membrane translocase complex IPI,IBA 15044455
genes like me logo Genes that share ontologies with TIMM50: view

Pathways & Interactions for TIMM50 Gene

PathCards logo

SuperPathways for TIMM50 Gene

genes like me logo Genes that share pathways with TIMM50: view

Pathways by source for TIMM50 Gene

2 Reactome pathways for TIMM50 Gene

Gene Ontology (GO) - Biological Process for TIMM50 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001836 release of cytochrome c from mitochondria IDA 15044455
GO:0006470 protein dephosphorylation IDA 15044455
GO:0007006 mitochondrial membrane organization IMP 15044455
GO:0015031 protein transport IEA --
GO:0030150 protein import into mitochondrial matrix IBA 21873635
genes like me logo Genes that share ontologies with TIMM50: view

No data available for SIGNOR curated interactions for TIMM50 Gene

Drugs & Compounds for TIMM50 Gene

No Compound Related Data Available

Transcripts for TIMM50 Gene

mRNA/cDNA for TIMM50 Gene

2 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
19 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIMM50

Alternative Splicing Database (ASD) splice patterns (SP) for TIMM50 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4a · 4b · 4c ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8a · 8b · 8c ^ 9a · 9b ^ 10a · 10b · 10c · 10d
SP1: - - -
SP2: - - -
SP3:
SP4: - - - -
SP5: - -
SP6:
SP7: - - - - - - - - - - -
SP8: - - - - - - - - - - -

Relevant External Links for TIMM50 Gene

GeneLoc Exon Structure for
TIMM50

Expression for TIMM50 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TIMM50 Gene

Protein differential expression in normal tissues from HIPED for TIMM50 Gene

This gene is overexpressed in Bone (21.0) and Nasal epithelium (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TIMM50 Gene



Protein tissue co-expression partners for TIMM50 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TIMM50

SOURCE GeneReport for Unigene cluster for TIMM50 Gene:

Hs.590956

mRNA Expression by UniProt/SwissProt for TIMM50 Gene:

Q3ZCQ8-TIM50_HUMAN
Tissue specificity: Widely expressed. Expressed at higher level in brain, kidney and liver (at protein level).

Evidence on tissue expression from TISSUES for TIMM50 Gene

  • Pancreas(4.9)
  • Nervous system(4.6)
  • Eye(4.3)
genes like me logo Genes that share expression patterns with TIMM50: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for TIMM50 Gene

Orthologs for TIMM50 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TIMM50 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TIMM50 31 30
  • 99.34 (n)
OneToOne
cow
(Bos Taurus)
Mammalia TIMM50 31 30
  • 90.75 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Timm50 17 31 30
  • 87.91 (n)
rat
(Rattus norvegicus)
Mammalia LOC687295 30
  • 87.91 (n)
dog
(Canis familiaris)
Mammalia TIMM50 31 30
  • 86.39 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia TIMM50 31
  • 80 (a)
OneToOne
chicken
(Gallus gallus)
Aves TIMM50 31 30
  • 75.65 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TIMM50 31
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia timm50 30
  • 67.09 (n)
Str.1790 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.8302 30
zebrafish
(Danio rerio)
Actinopterygii timm50 31 30
  • 65.72 (n)
OneToOne
zgc66357 30
fruit fly
(Drosophila melanogaster)
Insecta ttm50 31 30
  • 53.23 (n)
OneToMany
ttm3 31
  • 38 (a)
OneToMany
ttm2 31
  • 32 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP001108 30
  • 50.11 (n)
worm
(Caenorhabditis elegans)
Secernentea scpl-4 31
  • 30 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes TIM50 31
  • 22 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3116 31
  • 42 (a)
OneToOne
Species where no ortholog for TIMM50 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for TIMM50 Gene

ENSEMBL:
Gene Tree for TIMM50 (if available)
TreeFam:
Gene Tree for TIMM50 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TIMM50: view image

Paralogs for TIMM50 Gene

Paralogs for TIMM50 Gene

(1) SIMAP similar genes for TIMM50 Gene using alignment to 12 proteins:

  • TIM50_HUMAN
  • M0QXC3_HUMAN
  • M0R003_HUMAN
  • M0R047_HUMAN
  • M0R0C3_HUMAN
  • M0R1Y4_HUMAN
  • M0R2D2_HUMAN
  • M0R2F8_HUMAN
  • M0R2Q2_HUMAN
  • M0R2Z3_HUMAN
  • M0R303_HUMAN
  • Q0VAB1_HUMAN
genes like me logo Genes that share paralogs with TIMM50: view

Variants for TIMM50 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TIMM50 Gene

SNP ID Clinical significance and condition Chr 19 pos Variation AA Info Type
780558 Benign: not provided 39,480,879(+) C/G MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT
rs1244226820 Pathogenic: 3-METHYLGLUTACONIC ACIDURIA, TYPE IX. 3-methylglutaconic aciduria 9 (MGCA9) [MIM:617698] 39,485,761(+) C/Tp.Thr149Met MISSENSE_VARIANT
rs1300848445 Pathogenic: 3-METHYLGLUTACONIC ACIDURIA, TYPE IX. 3-methylglutaconic aciduria 9 (MGCA9) [MIM:617698] 39,485,570(+) C/Tp.Arg114Trp MISSENSE_VARIANT,INTRON_VARIANT
rs1305711807 Pathogenic: 3-METHYLGLUTACONIC ACIDURIA, TYPE IX 39,486,463(+) G/A MISSENSE_VARIANT
rs1449758112 Pathogenic: 3-METHYLGLUTACONIC ACIDURIA, TYPE IX 39,488,079(+) C/T MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for TIMM50 Gene

Structural Variations from Database of Genomic Variants (DGV) for TIMM50 Gene

Variant ID Type Subtype PubMed ID
nsv523856 CNV loss 19592680
nsv953573 CNV deletion 24416366

Variation tolerance for TIMM50 Gene

Residual Variation Intolerance Score: 44.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.23; 69.99% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TIMM50 Gene

Human Gene Mutation Database (HGMD)
TIMM50
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TIMM50

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TIMM50 Gene

Disorders for TIMM50 Gene

MalaCards: The human disease database

(6) MalaCards diseases for TIMM50 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
3-methylglutaconic aciduria, type ix
  • mgca9
3-methylglutaconic aciduria
  • 3-methyl glutaconic aciduria
3-methylglutaconic aciduria, type v
  • mgca5
sengers syndrome
  • mitochondrial dna depletion syndrome 10 ; mtdps10
mohr-tranebjaerg syndrome
  • dds
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

TIM50_HUMAN
  • 3-methylglutaconic aciduria 9 (MGCA9) [MIM:617698]: An autosomal recessive disease characterized by early-onset seizures, severely delayed psychomotor development and intellectual disability. Patients have hypotonia or spasticity, and laboratory investigations show increased serum lactate and 3-methylglutaconic aciduria. {ECO:0000269 PubMed:27573165}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for TIMM50

genes like me logo Genes that share disorders with TIMM50: view

No data available for Genatlas for TIMM50 Gene

Publications for TIMM50 Gene

  1. Tim50, a component of the mitochondrial translocator, regulates mitochondrial integrity and cell death. (PMID: 15044455) Guo Y … Alnemri ES (The Journal of biological chemistry 2004) 3 4 23 54
  2. Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations. (PMID: 27573165) Shahrour MA … Malicdan MC (Clinical genetics 2017) 3 4 54
  3. Methylation-controlled J-protein MCJ acts in the import of proteins into human mitochondria. (PMID: 23263864) Schusdziarra C … Hell K (Human molecular genetics 2013) 3 4 54
  4. Inner mitochondrial translocase Tim50 interacts with 3β-hydroxysteroid dehydrogenase type 2 to regulate adrenal and gonadal steroidogenesis. (PMID: 21930695) Pawlak KJ … Bose HS (The Journal of biological chemistry 2011) 2 3 54
  5. Tim50a, a nuclear isoform of the mitochondrial Tim50, interacts with proteins involved in snRNP biogenesis. (PMID: 16008839) Xu H … Hebert MD (BMC cell biology 2005) 3 4 54

Products for TIMM50 Gene

Sources for TIMM50 Gene