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O60220 (TIM8A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitochondrial import inner membrane translocase subunit Tim8 A
Alternative name(s):
Deafness dystonia protein 1
X-linked deafness dystonia protein
Gene names
Name:TIMM8A
Synonyms:DDP, DDP1, TIM8A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length97 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. Probably necessary for normal neurologic development. Ref.6 Ref.7 Ref.8 Ref.9

Subunit structure

Heterohexamer; composed of 3 copies of TIMM8A and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22.

Subcellular location

Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side Ref.8.

Tissue specificity

Highly expressed in fetal and adult brain, followed by fetal lung, liver and kidney. Also expressed in heart, placenta, lung, liver, kidney, pancreas, skeletal muscle and heart.

Domain

The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8A from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane By similarity.

Involvement in disease

Mohr-Tranebjaerg syndrome (MTS) [MIM:304700]: Recessive neurodegenerative syndrome characterized by postlingual progressive sensorineural deafness as the first presenting symptom in early childhood, followed by progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14 Ref.15

Jensen syndrome (JENSS) [MIM:311150]: X-linked disease characterized by deafness, blindness and muscle weakness.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the small Tim family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 9797Mitochondrial import inner membrane translocase subunit Tim8 A
PRO_0000193584

Regions

Motif43 – 6624Twin CX3C motif

Amino acid modifications

Modified residue871Phosphoserine By similarity
Modified residue941Phosphoserine Ref.10
Modified residue961Phosphoserine Ref.12
Disulfide bond43 ↔ 66 By similarity
Disulfide bond47 ↔ 62 By similarity

Natural variations

Natural variant661C → W in MTS; disrupts the assembly of the heterohexamer with TIMM13. Ref.13 Ref.14 Ref.15
VAR_010237

Experimental info

Sequence conflict621C → R in AAH70284. Ref.5

Sequences

Sequence LengthMass (Da)Tools
O60220 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: CB72822290F20AB0

FASTA9710,998
        10         20         30         40         50         60 
MDSSSSSSAA GLGAVDPQLQ HFIEVETQKQ RFQQLVHQMT ELCWEKCMDK PGPKLDSRAE 

        70         80         90 
ACFVNCVERF IDTSQFILNR LEQTQKSKPV FSESLSD 

« Hide

References

« Hide 'large scale' references
[1]"A novel X-linked gene, DDP, shows mutations in families with deafness (DFN-1), dystonia, mental deficiency and blindness."
Jin H., May M., Tranebjaerg L., Kendall E., Fontan G., Jackson J., Subramony S.H., Arena F., Lubs H., Smith S., Stevenson R., Schwartz C., Vetrie D.
Nat. Genet. 14:177-180(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Tongue.
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain, Kidney and Urinary bladder.
[6]"Human deafness dystonia syndrome is a mitochondrial disease."
Koehler C.M., Leuenberger D., Merchant S., Renold A., Junne T., Schatz G.
Proc. Natl. Acad. Sci. U.S.A. 96:2141-2146(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PROBABLE FUNCTION.
[7]"Mitochondria and dystonia: the movement disorder connection?"
Wallace D.C., Murdock D.G.
Proc. Natl. Acad. Sci. U.S.A. 96:1817-1819(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PROBABLE FUNCTION.
[8]"Role of the deafness dystonia peptide 1 (DDP1) in import of human Tim23 into the inner membrane of mitochondria."
Rothbauer U., Hofmann S., Muehlenbein N., Paschen S.A., Gerbitz K.-D., Neupert W., Brunner M., Bauer M.F.
J. Biol. Chem. 276:37327-37334(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, ZINC-BINDING, INTERACTION WITH TIMM13.
[9]"The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex."
Roesch K., Hynds P.J., Varga R., Tranebjaerg L., Koehler C.M.
Hum. Mol. Genet. 13:2101-2111(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"A de novo missense mutation in a critical domain of the X-linked DDP gene causes the typical deafness-dystonia-optic atrophy syndrome."
Tranebjaerg L., Hamel B.C.J., Gabreels F.J.M., Renier W.O., Van Ghelue M.
Eur. J. Hum. Genet. 8:464-467(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTS TRP-66.
[14]"Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex."
Roesch K., Curran S.P., Tranebjaerg L., Koehler C.M.
Hum. Mol. Genet. 11:477-486(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTS TRP-66.
[15]"The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1.TIM13 complexes in the mitochondrial intermembrane space."
Hofmann S., Rothbauer U., Muehlenbein N., Neupert W., Gerbitz K.-D., Brunner M., Bauer M.F.
J. Biol. Chem. 277:23287-23293(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MTS TRP-66.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U66035 mRNA. Translation: AAC15946.1.
AK312117 mRNA. Translation: BAG35053.1.
AL035422 Genomic DNA. Translation: CAB55875.1.
CH471115 Genomic DNA. Translation: EAX02854.1.
BC006994 mRNA. Translation: AAH06994.1.
BC015093 mRNA. Translation: AAH15093.1.
BC070284 mRNA. Translation: AAH70284.1.
CCDSCCDS14481.1.
RefSeqNP_004076.1. NM_004085.3.
UniGeneHs.447877.

3D structure databases

ProteinModelPortalO60220.
SMRO60220. Positions 29-84.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108042. 7 interactions.
IntActO60220. 4 interactions.
MINTMINT-2999881.
STRING9606.ENSP00000361993.

PTM databases

PhosphoSiteO60220.

Proteomic databases

MaxQBO60220.
PaxDbO60220.
PeptideAtlasO60220.
PRIDEO60220.

Protocols and materials databases

DNASU1678.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372902; ENSP00000361993; ENSG00000126953.
ENST00000599969; ENSP00000470340; ENSG00000268249.
GeneID1678.
KEGGhsa:1678.
UCSCuc004ehd.2. human.

Organism-specific databases

CTD1678.
GeneCardsGC0XM100600.
GeneReviewsTIMM8A.
HGNCHGNC:11817. TIMM8A.
HPAHPA003628.
MIM300356. gene.
304700. phenotype.
311150. phenotype.
neXtProtNX_O60220.
Orphanet3213. Deafness - opticoacoustic nerve atrophy - dementia.
52368. Mohr-Tranebjaerg syndrome.
PharmGKBPA36523.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238740.
HOGENOMHOG000115758.
HOVERGENHBG060492.
InParanoidO60220.
KOK17780.
OMAISEYERY.
OrthoDBEOG79W97P.
PhylomeDBO60220.
TreeFamTF106191.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

BgeeO60220.
CleanExHS_TIMM8A.
GenevestigatorO60220.

Family and domain databases

Gene3D1.10.287.810. 1 hit.
InterProIPR004217. Tim10/DDP_fam_Znf.
[Graphical view]
PfamPF02953. zf-Tim10_DDP. 1 hit.
[Graphical view]
SUPFAMSSF144122. SSF144122. 1 hit.
ProtoNetSearch...

Other

GeneWikiTIMM8A.
GenomeRNAi1678.
NextBio6906.
PROO60220.
SOURCESearch...

Entry information

Entry nameTIM8A_HUMAN
AccessionPrimary (citable) accession number: O60220
Secondary accession number(s): B2R5A6, Q6IRW6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM