Multipass transmembrane proteins are brought into mitochondria and inserted into the mitochondrial inner membrane by way of the TIM22 complex. This complex has six subunits and is a twin-pore translocase. The protein encoded by this gene is a subunit of TIM22 and represents the voltage-activated and signal-gated channel. [provided by RefSeq, Jul 2016] See more...

Aliases for TIMM22 Gene

Aliases for TIMM22 Gene

  • Translocase Of Inner Mitochondrial Membrane 22 2 3 5
  • TIM22 2 3 4
  • Mitochondrial Import Inner Membrane Translocase Subunit Tim22 3 4
  • Testis-Expressed Sequence 4 2 3
  • Testis-Expressed Protein 4 3 4
  • TEX4 3 4
  • Translocase Of Inner Mitochondrial Membrane 22 Homolog (Yeast) 2
  • Translocase Of Inner Mitochondrial Membrane 22 Homolog 3
  • COXPD43 3
  • TIMM22 5

External Ids for TIMM22 Gene

Previous HGNC Symbols for TIMM22 Gene

  • TEX4

Previous GeneCards Identifiers for TIMM22 Gene

  • GC17P001158
  • GC17P000853
  • GC17P000885
  • GC17P000847
  • GC17P000900

Summaries for TIMM22 Gene

Entrez Gene Summary for TIMM22 Gene

  • Multipass transmembrane proteins are brought into mitochondria and inserted into the mitochondrial inner membrane by way of the TIM22 complex. This complex has six subunits and is a twin-pore translocase. The protein encoded by this gene is a subunit of TIM22 and represents the voltage-activated and signal-gated channel. [provided by RefSeq, Jul 2016]

GeneCards Summary for TIMM22 Gene

TIMM22 (Translocase Of Inner Mitochondrial Membrane 22) is a Protein Coding gene. Diseases associated with TIMM22 include Combined Oxidative Phosphorylation Deficiency 43 and Sengers Syndrome. Among its related pathways are Metabolism of proteins and Mitochondrial protein import.

UniProtKB/Swiss-Prot Summary for TIMM22 Gene

  • Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps (By similarity).

Gene Wiki entry for TIMM22 Gene

Additional gene information for TIMM22 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TIMM22 Gene

Genomics for TIMM22 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TIMM22 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17J000996 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 618.6 +0.3 252 2.4 BRCA1 SP1 HNRNPL CREB1 CTCF TEAD4 ZNF629 TFE3 RFX1 SIX5 TIMM22 MYO1C RPA1 TLCD3A ENSG00000262228 GEMIN4 PRPF8 piR-31804 lnc-TIMM22-2 ABR
GH17J000997 Enhancer 0.3 ENCODE 600.7 -1.0 -1033 0.1 ZBTB11 ADNP TIMM22 lnc-TIMM22-1 lnc-TIMM22-2 NXN
GH17J000999 Enhancer 0.8 ENCODE dbSUPER 30 +6.0 5980 7.4 ZBTB33 POLR2A ZIC2 CTCF ZNF600 SOX13 TCF7 ZNF138 MYNN BHLHE40 piR-31804 TIMM22 NXN GLOD4 MYO1C INPP5K lnc-TIMM22-2 ABR
GH17J000713 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 10.6 -281.9 -281945 4 CREB1 GATAD2A PRDM10 ZNF629 TFE3 RFX1 RFX5 POLR2A BACH1 ZHX2 VPS53 lnc-FAM57A-5 lnc-GEMIN4-3 PRPF8 TLCD3A ENSG00000262228 DBIL5P TIMM22 GLOD4 NXN
GH17J000750 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 10.5 -245.0 -244994 3.9 SP1 GATAD2A CTCF ZNF629 IKZF1 ZNF692 POLR2A ZNF174 BACH1 TARDBP DBIL5P VPS53 GEMIN4 lnc-FAM57A-4 piR-49449 TLCD3A PRPF8 MRM3 GLOD4 TIMM22
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TIMM22 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TIMM22

Top Transcription factor binding sites by QIAGEN in the TIMM22 gene promoter:
  • AREB6
  • ATF
  • CUTL1
  • FOXO1
  • FOXO1a
  • MIF-1
  • STAT1
  • STAT1alpha
  • STAT1beta
  • STAT3

Genomic Locations for TIMM22 Gene

Genomic Locations for TIMM22 Gene
chr17:997,129-1,003,671
(GRCh38/hg38)
Size:
6,543 bases
Orientation:
Plus strand
chr17:900,357-906,911
(GRCh37/hg19)
Size:
6,555 bases
Orientation:
Plus strand

Genomic View for TIMM22 Gene

Genes around TIMM22 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIMM22 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIMM22 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TIMM22 Gene

Proteins for TIMM22 Gene

  • Protein details for TIMM22 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y584-TIM22_HUMAN
    Recommended name:
    Mitochondrial import inner membrane translocase subunit Tim22
    Protein Accession:
    Q9Y584
    Secondary Accessions:
    • Q9NWI8

    Protein attributes for TIMM22 Gene

    Size:
    194 amino acids
    Molecular mass:
    20031 Da
    Quaternary structure:
    • Component of the TIM22 complex, whose core is composed of TIMM22, associated with peripheral protein FXC1/TIMM10B and the 70 kDa heterohexamer (PubMed:14726512, PubMed:27265872). In most cases, the 70 kDa complex is composed of TIMM9 and TIMM10 (TIMM10A or TIMM10B) (PubMed:14726512). A small fraction of the 70 kDa complex is composed of TIMM8 (TIMM8A/DDP1 or TIMM8B/DDP2) and TIMM13 (PubMed:14726512). The TIM22 complex also contains AGK and TIMM29 (PubMed:27718247, PubMed:28712724, PubMed:28712726). Interacts directly with TIMM9, TIMM10A and FXC1/TIMM10B (PubMed:14726512). Interacts (when oxidized) with TIMM29; interaction is direct (PubMed:27718247).

neXtProt entry for TIMM22 Gene

Post-translational modifications for TIMM22 Gene

  • Disulfide bonds promote efficient assembly of the TIM22 complex.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for TIMM22 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TIMM22 Gene

Domains & Families for TIMM22 Gene

Gene Families for TIMM22 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for TIMM22 Gene

InterPro:
Blocks:
  • Mitochondrial import inner membrane translocase, subunit Tim17/22
ProtoNet:

Suggested Antigen Peptide Sequences for TIMM22 Gene

GenScript: Design optimal peptide antigens:
  • Testis-expressed sequence 4 (TIM22_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y584

UniProtKB/Swiss-Prot:

TIM22_HUMAN :
  • Belongs to the Tim17/Tim22/Tim23 family.
Family:
  • Belongs to the Tim17/Tim22/Tim23 family.
genes like me logo Genes that share domains with TIMM22: view

Function for TIMM22 Gene

Molecular function for TIMM22 Gene

UniProtKB/Swiss-Prot Function:
Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps (By similarity).

Phenotypes From GWAS Catalog for TIMM22 Gene

Gene Ontology (GO) - Molecular Function for TIMM22 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 27718247
GO:0008320 protein transmembrane transporter activity TAS 14726512
GO:0030943 mitochondrion targeting sequence binding IBA 21873635
genes like me logo Genes that share ontologies with TIMM22: view
genes like me logo Genes that share phenotypes with TIMM22: view

Animal Models for TIMM22 Gene

MGI Knock Outs for TIMM22:
  • Timm22 Timm22<tm1b(KOMP)Wtsi>

Animal Model Products

  • Taconic Biosciences Mouse Models for TIMM22

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIMM22

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TIMM22 Gene

Localization for TIMM22 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIMM22 Gene

Mitochondrion inner membrane. Multi-pass membrane protein.

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 TIMM22 gene
Compartment Confidence
mitochondrion 5
cytosol 2
extracellular 1
cytoskeleton 1
nucleus 1
endoplasmic reticulum 1
plasma membrane 0
peroxisome 0

Gene Ontology (GO) - Cellular Components for TIMM22 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA --
GO:0005743 mitochondrial inner membrane TAS 14726512
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0042721 TIM22 mitochondrial import inner membrane insertion complex IBA,IDA 27718247
genes like me logo Genes that share ontologies with TIMM22: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for TIMM22 Gene

Pathways & Interactions for TIMM22 Gene

PathCards logo

SuperPathways for TIMM22 Gene

genes like me logo Genes that share pathways with TIMM22: view

Pathways by source for TIMM22 Gene

2 Reactome pathways for TIMM22 Gene

Gene Ontology (GO) - Biological Process for TIMM22 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006626 protein targeting to mitochondrion TAS --
GO:0015031 protein transport IEA --
GO:0045039 protein import into mitochondrial inner membrane IDA,TAS 14726512
GO:0071806 protein transmembrane transport IEA --
genes like me logo Genes that share ontologies with TIMM22: view

No data available for SIGNOR curated interactions for TIMM22 Gene

Drugs & Compounds for TIMM22 Gene

No Compound Related Data Available

Transcripts for TIMM22 Gene

mRNA/cDNA for TIMM22 Gene

1 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
1 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 TIMM22

Alternative Splicing Database (ASD) splice patterns (SP) for TIMM22 Gene

No ASD Table

Relevant External Links for TIMM22 Gene

GeneLoc Exon Structure for
TIMM22

Expression for TIMM22 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TIMM22 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

  • Ovary (Reproductive System)

Protein differential expression in normal tissues from HIPED for TIMM22 Gene

This gene is overexpressed in Tlymphocyte (10.2) and Fetal testis (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TIMM22 Gene



Protein tissue co-expression partners for TIMM22 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TIMM22

SOURCE GeneReport for Unigene cluster for TIMM22 Gene:

Hs.745034

Evidence on tissue expression from TISSUES for TIMM22 Gene

  • Lung(4.2)
genes like me logo Genes that share expression patterns with TIMM22: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TIMM22 Gene

Orthologs for TIMM22 Gene

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

Orthologs for TIMM22 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TIMM22 30 31
  • 98.8 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TIMM22 30 31
  • 91.58 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TIMM22 30 31
  • 90.45 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TIMM22 31
  • 89 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Timm22 30 17 31
  • 88.49 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Timm22 30
  • 88.48 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia TIMM22 31
  • 88 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TIMM22 30 31
  • 78.01 (n)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia timm22 30
  • 76.03 (n)
Zebrafish
(Danio rerio)
Actinopterygii TIMM22 31
  • 74 (a)
OneToOne
LOC100537779 30
  • 71.6 (n)
Fruit Fly
(Drosophila melanogaster)
Insecta CG31229 30 31
  • 57.38 (n)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003199 30
  • 56.35 (n)
Worm
(Caenorhabditis elegans)
Secernentea CELE_C47G2.3 30
  • 50.47 (n)
C47G2.3 31
  • 34 (a)
OneToOne
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes TIM22 31 33
  • 29 (a)
OneToOne
Fission Yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes tim22 30
  • 52.42 (n)
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.2638 31
  • 42 (a)
OneToOne
Species where no ortholog for TIMM22 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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 TIMM22 Gene

ENSEMBL:
Gene Tree for TIMM22 (if available)
TreeFam:
Gene Tree for TIMM22 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TIMM22: view image

Paralogs for TIMM22 Gene

No data available for Paralogs for TIMM22 Gene

Variants for TIMM22 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TIMM22 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
708129 Benign: not provided 997,187(+) A/G SYNONYMOUS_VARIANT
869639 Pathogenic: COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 43 997,239(+) G/C MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for TIMM22 Gene

Structural Variations from Database of Genomic Variants (DGV) for TIMM22 Gene

Variant ID Type Subtype PubMed ID
dgv172n21 CNV gain 19592680
dgv3079n100 CNV gain 25217958
dgv3080n100 CNV gain 25217958
esv2422420 CNV duplication 17116639
esv2751769 CNV gain 17911159
esv2758673 CNV gain 17122850
esv3572275 CNV gain 25503493
esv3582465 CNV loss 25503493
esv3639665 CNV gain 21293372
nsv1059578 CNV gain 25217958
nsv1064415 CNV gain 25217958
nsv1066149 CNV gain 25217958
nsv469582 CNV loss 16826518
nsv470566 CNV loss 18288195
nsv574142 CNV gain 21841781
nsv827852 CNV gain 20364138
nsv952095 CNV deletion 24416366

Variation tolerance for TIMM22 Gene

Residual Variation Intolerance Score: 42.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.93; 19.27% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TIMM22 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TIMM22

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TIMM22 Gene

Disorders for TIMM22 Gene

MalaCards: The human disease database

(3) MalaCards diseases for TIMM22 Gene - From: OMIM, ClinVar, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
combined oxidative phosphorylation deficiency 43
  • coxpd43
sengers syndrome
  • mitochondrial dna depletion syndrome 10 ; mtdps10
mohr-tranebjaerg syndrome
  • dds
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for TIMM22

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TIMM22: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TIMM22 Gene

Publications for TIMM22 Gene

  1. Organization and function of the small Tim complexes acting along the import pathway of metabolite carriers into mammalian mitochondria. (PMID: 14726512) Mühlenbein N … Bauer MF (The Journal of biological chemistry 2004) 2 3 4
  2. The mitochondrial TIM22 preprotein translocase is highly conserved throughout the eukaryotic kingdom. (PMID: 10611480) Bauer MF … Hofmann S (FEBS letters 1999) 2 3 4
  3. Acylglycerol Kinase Mutated in Sengers Syndrome Is a Subunit of the TIM22 Protein Translocase in Mitochondria. (PMID: 28712724) Vukotic M … Langer T (Molecular cell 2017) 3 4
  4. Sengers Syndrome-Associated Mitochondrial Acylglycerol Kinase Is a Subunit of the Human TIM22 Protein Import Complex. (PMID: 28712726) Kang Y … Stojanovski D (Molecular cell 2017) 3 4
  5. The presence of disulfide bonds reveals an evolutionarily conserved mechanism involved in mitochondrial protein translocase assembly. (PMID: 27265872) Wrobel L … Chacinska A (Scientific reports 2016) 3 4

Products for TIMM22 Gene

  • Signalway Proteins for TIMM22

Sources for TIMM22 Gene