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APTX

Protein FULL name:

aprataxin isoform a [Homo sapiens].


APTX (Homo sapiens) is product of expression of APTX gene.

Human diseases related to this protein:

APTX is involved in:

BER in Homo sapiens
     


Keywords:



FUNCTION: DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non- ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. Also able to hydrolyze adenosine 5'- monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity.

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=18 uM for AppppA; KM=837.5 uM for AMP-NH(2);

SUBUNIT: Interacts with single-strand break repair proteins XRCC1, XRCC4, ADPRT and p53/TP53. Interacts with NCL.

INTERACTION: P09874:PARP1; NbExp=1; IntAct=EBI-847814, EBI-355676;

SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Nucleus, nucleolus. Note=Upon genotoxic stress, colocalizes with XRCC1 at sites of DNA damage. Interaction with NCL is required for nucleolar localization.

TISSUE SPECIFICITY: Widely expressed. In brain, it is expressed in the posterior cortex, cerebellum, hippocampus and olfactory bulb. Isoform 1 is highly expressed in the cerebral cortex and cerebellum, compared to isoform 2.

DOMAIN: The histidine triad, also called HIT motif, forms part of the binding loop for the alpha-phosphate of purine mononucleotide (By similarity).

DOMAIN: The FHA-like domain mediates interaction with NCL; XRCC1 and XRCC4.

DOMAIN: The HIT domain is required for enzymatic activity.

DOMAIN: The C2H2-type zinc finger mediates DNA-binding.

DISEASE: Defects in APTX are the cause of ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920]. AOA is an autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.

DISEASE: Defects in APTX are a cause of coenzyme Q10 deficiency [MIM:607426]. Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations. It can be associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction and an ataxic form with cerebellar atrophy. Coenzyme Q10 deficiency due to APTX mutations is typically associated with cerebellar ataxia.

SIMILARITY: Contains 1 C2H2-type zinc finger.

SIMILARITY: Contains 1 FHA-like domain.

SIMILARITY: Contains 1 HIT domain.

WEB RESOURCE: Name=GeneReviews; [LINK]


NCBI GenPept GI number(s): 28329436
8923156
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q7Z2E3 Q7Z2E3
PFAM: - Q7Z2E3 (Link - using uniprot id)
InterPro: - Q7Z2E3 (Link - using uniprot id)
CATH: None  
SCOP: None  
PDB: - -


Protein sequence:
MMRVCWLVRQDSRHQRIRLPHLEAVVIGRGPETKITDKKCSRQQVQLKAE
CNKGYVKVKQVGVNPTSIDSVVIGKDQEVKLQPGQVLHMVNELYPYIVEF
EEEAKNPGLETHRKRKRSGNSDSIERDAAQEAEAGTGLEPGSNSGQCSVP
LKKGKDAPIKKESLGHWSQGLKISMQDPKMQVYKDEQVVVIKDKYPKARY
HWLVLPWTSISSLKAVAREHLELLKHMHTVGEKVIVDFAGSSKLRFRLGY
HAIPSMSHVHLHVISQDFDSPCLKNKKHWNSFNTEYFLESQAVIEMVQEA
GRVTVRDGMPELLKLPLRCHECQQLLPSIPQLKEHLRKHWTQ

APTX (Homo sapiens) is able to recognize following damages:
References:

Title Authors Journal
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Date H, Onodera O, Tanaka H, Iwabuchi K, Uekawa K, Igarashi S, Koike R, Hiroi T, Yuasa T, Awaya Y, Sakai T, Takahashi T, Nagatomo H, Sekijima Y, Kawachi I, Takiyama Y, Nishizawa M, Fukuhara N, Saito K, Sugano S, Tsuji S Nat Genet Oct. 1, 2001
The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Moreira MC, Barbot C, Tachi N, Kozuka N, Uchida E, Gibson T, Mendonca P, Costa M, Barros J, Yanagisawa T, Watanabe M, Ikeda Y, Aoki M, Nagata T, Coutinho P, Sequeiros J, Koenig M Nat Genet Oct. 1, 2001
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the aprataxin gene mutations. Shimazaki H, Takiyama Y, Sakoe K, Ikeguchi K, Niijima K, Kaneko J, Namekawa M, Ogawa T, Date H, Tsuji S, Nakano I, Nishizawa M Neurology Aug. 27, 2002
Phenotypic variability of aprataxin gene mutations. Tranchant C, Fleury M, Moreira MC, Koenig M, Warter JM Neurology March 11, 2003
Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Le Ber I, Moreira MC, Rivaud-Pechoux S, Chamayou C, Ochsner F, Kuntzer T, Tardieu M, Said G, Habert MO, Demarquay G, Tannier C, Beis JM, Brice A, Koenig M, Durr A Brain Dec. 1, 2003
Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein. Sano Y, Date H, Igarashi S, Onodera O, Oyake M, Takahashi T, Hayashi S, Morimatsu M, Takahashi H, Makifuchi T, Fukuhara N, Tsuji S Ann Neurol Jan. 1, 2004
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, 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 TO, 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 Feb. 1, 2004
Aprataxin, a novel protein that protects against genotoxic stress. Gueven N, Becherel OJ, Kijas AW, Chen P, Howe O, Rudolph JH, Gatti R, Date H, Onodera O, Taucher-Scholz G, Lavin MF Hum Mol Genet May 15, 2004
DNA sequence and analysis of human chromosome 9. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I Nature May 27, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. Clements PM, Breslin C, Deeks ED, Byrd PJ, Ju L, Bieganowski P, Brenner C, Moreira MC, Taylor AM, Caldecott KW DNA Repair (Amst) Nov. 2, 2004
Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Quinzii CM, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S, Hirano M Neurology Jan. 8, 2005
Very late onset in ataxia oculomotor apraxia type I. Criscuolo C, Mancini P, Menchise V, Sacca F, De Michele G, Banfi S, Filla A Ann Neurol May 1, 2005
Aprataxin forms a discrete branch in the HIT (histidine triad) superfamily of proteins with both DNA/RNA binding and nucleotide hydrolase activities. Kijas AW, Harris JL, Harris JM, Lavin MF J Biol Chem May 19, 2006
Nucleolar localization of aprataxin is dependent on interaction with nucleolin and on active ribosomal DNA transcription. Becherel OJ, Gueven N, Birrell GW, Schreiber V, Suraweera A, Jakob B, Taucher-Scholz G, Lavin MF Hum Mol Genet July 15, 2006
The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Ahel I, Rass U, El-Khamisy SF, Katyal S, Clements PM, McKinnon PJ, Caldecott KW, West SC Nature Oct. 12, 2006
The full-ORF clone resource of the German cDNA Consortium. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I BMC Genomics Jan. 1, 2007
Actions of aprataxin in multiple DNA repair pathways. Rass U, Ahel I, West SC J Biol Chem March 1, 2007


Last modification of this entry: Oct. 11, 2010.

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