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Description:
Aprataxin (Forkhead-associated domain histidine triad-like protein)(FHA-HIT).
Molecular weight: 40740
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
single strand break repair( GO:0000012 ) DNA repair( GO:0006281 ) base-excision repair( GO:0006284 )
Important dates:
07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
07-JUN-2004, sequence version 2.
21-FEB-2006, entry version 22.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein APTX_HUMAN:
Keywords:
Alternative splicing; Disease mutation; DNA damage; DNA repair; Metal-binding; Neurodegeneration; Nuclear protein; Zinc; Zinc-finger.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Huang C.-H.;
RT "Identification of FHA-HIT as a novel nuclear protein involved in
RT cell-cycle regulation.";
RL Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8 AND 10).
RC TISSUE=Hypothalamus, Kidney, Lung adenocarcinoma, Lymphoma, Melanoma,
RC Muscle, Retinoblastoma, Skin, and Testis;
RA Chen Y., Huang C.-H.;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9).
RC TISSUE=Endometrium;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-261 (ISOFORMS 2; 4; 5 AND 7).
RC TISSUE=Brain;
RA Hellenbroich Y., Habeck M.;
RT "Mutations in the APTX gene.";
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP DISEASE, TISSUE SPECIFICITY, AND VARIANTS AOA1 LEU-220 AND GLY-277.
RX PubMed=11586299; DOI=10.1038/ng1001-184;
RA Date H., Onodera O., Tanaka H., Iwabuchi K., Uekawa K., Igarashi S.,
RA Koike R., Hiroi T., Yuasa T., Awaya Y., Sakai T., Takahashi T.,
RA Nagatomo H., Sekijima Y., Kawachi I., Takiyama Y., Nishizawa M.,
RA Fukuhara N., Saito K., Sugano S., Tsuji S.;
RT "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is
RT caused by mutations in a new HIT superfamily gene.";
RL Nat. Genet. 29:184-188(2001).
RN [9]
RP DISEASE, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, AND VARIANTS AOA1
RP HIS-213 AND LEU-220.
RX PubMed=11586300; DOI=10.1038/ng1001-189;
RA Moreira M.-C., Barbot C., Tachi N., Kozuka N., Uchida E., Gibson T.,
RA Mendonca P., Costa M., Barros J., Yanagisawa T., Watanabe M.,
RA Ikeda Y., Aoki M., Nagata T., Coutinho P., Sequeiros J., Koenig M.;
RT "The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-
RT finger protein aprataxin.";
RL Nat. Genet. 29:189-193(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION
RP WITH XRCC1.
RX PubMed=14755728; DOI=10.1002/ana.10808;
RA Sano Y., Date H., Igarashi S., Onodera O., Oyake M., Takahashi T.,
RA Hayashi S., Morimatsu M., Takahashi H., Makifuchi T., Fukuhara N.,
RA Tsuji S.;
RT "Aprataxin, the causative protein for EAOH is a nuclear protein with a
RT potential role as a DNA repair protein.";
RL Ann. Neurol. 55:241-249(2004).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTIONS WITH XRCC1; ADPRT;
RP TP53 AND NCL.
RX PubMed=15044383; DOI=10.1093/hmg/ddh122;
RA Gueven N., Becherel O.J., Kijas A.W., Chen P., Howe O., Rudolph J.H.,
RA Gatti R., Date H., Onodera O., Taucher-Scholz G., Lavin M.F.;
RT "Aprataxin, a novel protein that protects against genotoxic stress.";
RL Hum. Mol. Genet. 13:1081-1093(2004).
RN [12]
RP VARIANT AOA1 ARG-215.
RA Shimazaki H., Takiyama Y., Sakoe K., Ikeguchi K., Niijima K.,
RA Kaneko J., Namekawa M., Ogawa T., Date H., Tsuji S., Nakano I.,
RA Nishizawa M.;
RT "Early-onset ataxia with ocular motor apraxia and hypoalbuminemia: the
RT aprataxin gene mutations.";
RL Neurology 59:590-595(2002).
RN [13]
RP VARIANT AOA1 GLN-211.
RA Tranchant C., Fleury M., Moreira M.-C., Koenig M., Warter J.-M.;
RT "Phenotypic variability of aprataxin gene mutations.";
RL Neurology 60:868-870(2003).
RN [14]
RP VARIANTS AOA1 VAL-212; GLY-277 AND ARG-293.
RX PubMed=14506070; DOI=10.1093/brain/awg283;
RA Le Ber I., Moreira M.-C., Rivaud-Pechoux S., Chamayou C., Ochsner F.,
RA Kuntzer T., Tardieu M., Saied G., Habert M.-O., Demarquay G.,
RA Tannier C., Beis J.-M., Brice A., Koenig M., Duerr A.;
RT "Cerebellar ataxia with oculomotor apRAxia type 1: clinical and
RT genetic studies.";
RL Brain 126:2761-2772(2003).
RN [15]
RP VARIANT AOA1 PRO-237.
RX PubMed=15852392; DOI=10.1002/ana.20463;
RA Criscuolo C., Mancini P., Menchise V., Sacca F., De Michele G.,
RA Banfi S., Filla A.;
RT "Very late onset in ataxia oculomotor apraxia type I.";
RL Ann. Neurol. 57:777-777(2005).
RN [16]
RP INVOLVEMENT IN COENZYME Q DEFICIENCY.
RX PubMed=15699391; DOI=10.1212/01.WNL.0000150588.75281.58;
RA Quinzii C.M., Kattah A.G., Naini A., Akman H.O., Mootha V.K.,
RA DiMauro S., Hirano M.;
RT "Coenzyme Q deficiency and cerebellar ataxia associated with an
RT aprataxin mutation.";
RL Neurology 64:539-541(2005).
Feature:
CHAIN 1 356 Aprataxin.
/FTId=PRO_0000109838.
DOMAIN 38 87 FHA-like.
DOMAIN 182 287 HIT.
ZN_FING 331 353 C2H2-type.
REGION 1 110 Interactions with ADPRT and NCL.
MOTIF 126 131 Nuclear localization signal (Probable).
VARSPLIC 1 193 Missing (in isoform 6).
/FTId=VSP_010534.
VARSPLIC 1 188 Missing (in isoform 2).
/FTId=VSP_010535.
VARSPLIC 1 102 Missing (in isoform 4).
/FTId=VSP_010536.
VARSPLIC 1 14 Missing (in isoform 5, isoform 7 and
isoform 9).
/FTId=VSP_010537.
VARSPLIC 59 112 Missing (in isoform 5 and isoform 10).
/FTId=VSP_010538.
VARSPLIC 104 175 Missing (in isoform 3).
/FTId=VSP_010539.
VARSPLIC 175 193 Missing (in isoform 8).
/FTId=VSP_010540.
VARSPLIC 306 356 AVIEMVQEAGRVTVRDGMPELLKLPLRCHECQQLLPSIPQL
KEHLRKHWTQ -> E (in isoform 6 and isoform
9).
/FTId=VSP_010541.
VARIANT 211 211 K -> Q (in AOA1; it probably does not
greatly affect the protein;
heterozygous).
/FTId=VAR_018794.
VARIANT 212 212 A -> V (in AOA1; heterozygous).
/FTId=VAR_018795.
VARIANT 213 213 R -> H (in AOA1; in a Portuguese family).
/FTId=VAR_018796.
VARIANT 215 215 H -> R (in AOA1; in a Japanese brother
and sister born of consanguineous
parents).
/FTId=VAR_018797.
VARIANT 220 220 P -> L (in AOA1; frequent variant in
unrelated families).
/FTId=VAR_018798.
VARIANT 237 237 L -> P (in AOA1).
/FTId=VAR_025365.
VARIANT 277 277 V -> G (in AOA1; in a family).
/FTId=VAR_018799.
VARIANT 281 281 D -> G (in AOA1; heterozygous).
/FTId=VAR_018800.
VARIANT 293 293 W -> R (in AOA1; heterozygous).
/FTId=VAR_018801.
Comments:
-!- FUNCTION: Probably involved in the repair of DNA single-stand
breaks, or in response to DNA single-stand breaks.
-!- SUBUNIT: Interacts with single-strand break repair proteins XRCC1,
ADPRT and p53/TP53. Interacts with NCL.
-!- SUBCELLULAR LOCATION: Nuclear. Upon genotoxic stress, it
colocalizes with XRCC1 at sites of DNA damage.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=10;
Name=1; Synonyms=Long;
IsoId=Q7Z2E3-1; Sequence=Displayed;
Note=Major form;
Name=2; Synonyms=Short;
IsoId=Q7Z2E3-2; Sequence=VSP_010535;
Note=Minor form;
Name=3;
IsoId=Q7Z2E3-3; Sequence=VSP_010539;
Note=May be an aberrant isoform present in cancer cell lines;
Name=4;
IsoId=Q7Z2E3-4; Sequence=VSP_010536;
Note=May be an aberrant isoform present in cancer cell lines;
Name=5;
IsoId=Q7Z2E3-5; Sequence=VSP_010537, VSP_010538;
Note=May be an aberrant isoform present in cancer cell lines;
Name=6;
IsoId=Q7Z2E3-6; Sequence=VSP_010534, VSP_010541;
Note=May be an aberrant isoform present in cancer cell lines;
Name=7;
IsoId=Q7Z2E3-7; Sequence=VSP_010537;
Note=May be an aberrant isoform present in cancer cell lines;
Name=8;
IsoId=Q7Z2E3-8; Sequence=VSP_010540;
Note=May be an aberrant isoform present in cancer cell lines;
Name=9;
IsoId=Q7Z2E3-9; Sequence=VSP_010537, VSP_010541;
Note=No experimental confirmation available;
Name=10;
IsoId=Q7Z2E3-10; Sequence=VSP_010538;
Note=May be an aberrant isoform present in cancer cell lines;
-!- 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.
-!- DISEASE: Defects in APTX are the cause of ataxia-oculomotor
apraxia 1 (AOA1) [MIM:208920]. AOA1 is an autosomal recessive
syndrome characterized by early-onset cerebellar ataxia,
oculomotor apraxia, early areflexia and late peripheral
neuropathy. Ataxia, oculomotor apraxia and cerebral atrophy are
major clinical features of AOA1 patients that are also observed in
patients with ataxia-telangiectasia (A-T). The most debilitating
feature of this syndrome is the progressive neurodegeneration
associated with loss of Purkinje cells and ectopic location of
these cells in the molecular layer. The loss of Purkinje cells has
also been associated with AOA1.
-!- 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.
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Sequence length: 356
MSNVNLSVSD FWRVMMRVCW LVRQDSRHQR IRLPHLEAVV IGRGPETKIT DKKCSRQQVQ
LKAECNKGYV KVKQVGVNPT SIDSVVIGKD QEVKLQPGQV LHMVNELYPY IVEFEEEAKN
PGLETHRKRK RSGNSDSIER DAAQEAEAGT GLEPGSNSGQ CSVPLKKGKD APIKKESLGH
WSQGLKISMQ DPKMQVYKDE QVVVIKDKYP KARYHWLVLP WTSISSLKAV AREHLELLKH
MHTVGEKVIV DFAGSSKLRF RLGYHAIPSM SHVHLHVISQ DFDSPCLKNK KHWNSFNTEY
FLESQAVIEM VQEAGRVTVR DGMPELLKLP LRCHECQQLL PSIPQLKEHL RKHWTQ