Q7Z2E3 (APTX_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aprataxin
EC=3.-.-.-

Alternative name(s):
Forkhead-associated domain histidine triad-like protein
Short name=FHA-HIT

Gene names

Name:	APTX
Synonyms:	AXA1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	356 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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-NH2) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity. Ref.11 Ref.13 Ref.15 Ref.16 Ref.17
Subunit structure	Interacts with single-strand break repair proteins XRCC1, XRCC4, ADPRT and p53/TP53. Interacts with NCL. Interacts (via FHA-like domain) with MDC1 (phosphorylated). Ref.11 Ref.12 Ref.13 Ref.14 Ref.18
Subcellular location	Nucleus › nucleoplasm. Nucleus › nucleolus. Note: Upon genotoxic stress, colocalizes with XRCC1 at sites of DNA damage. Colocalizes with MDC1 at sites of DNA double-strand breaks. Interaction with NCL is required for nucleolar localization. Ref.11 Ref.12 Ref.13 Ref.14 Ref.18
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. Ref.9 Ref.10 Ref.11
Domain	The histidine triad, also called HIT motif, forms part of the binding loop for the alpha-phosphate of purine mononucleotide By similarity. The FHA-like domain mediates interaction with NCL; XRCC1 and XRCC4. The HIT domain is required for enzymatic activity. The C2H2-type zinc finger mediates DNA-binding.
Involvement in 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. Ref.9 Ref.10 Ref.19 Ref.20 Ref.21 Ref.22 Defects in APTX are a cause of coenzyme Q10 deficiency (COQ10D) [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.
Sequence similarities	Contains 1 C2H2-type zinc finger. Contains 1 FHA-like domain. Contains 1 HIT domain.
Biophysicochemical properties	Kinetic parameters: KM=18 µM for AppppA KM=837.5 µM for AMP-NH2

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Neurodegeneration
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell death Inferred from electronic annotation. Source: UniProtKB-KW double-strand break repair Inferred from direct assay. Source: UniProtKB regulation of protein stability Inferred from mutant phenotype Ref.14. Source: UniProtKB response to hydrogen peroxide Inferred from direct assay Ref.13. Source: UniProtKB single strand break repair Inferred from direct assay Ref.11. Source: UniProtKB
Cellular component	chromatin Inferred from direct assay Ref.13. Source: UniProtKB nucleolus Inferred from direct assay Ref.13Ref.14. Source: UniProtKB nucleoplasm Inferred from direct assay Ref.13Ref.14. Source: UniProtKB
Molecular function	DNA 5'-adenosine monophosphate hydrolase activity Inferred from direct assay Ref.15Ref.16Ref.17. Source: UniProtKB chromatin binding Inferred from direct assay Ref.13. Source: UniProtKB damaged DNA binding Inferred from direct assay Ref.11. Source: UniProtKB double-stranded DNA binding Inferred from direct assay Ref.15Ref.17. Source: UniProtKB double-stranded RNA binding Inferred from direct assay Ref.15. Source: UniProtKB phosphoglycolate phosphatase activity Inferred from direct assay. Source: UniProtKB phosphoprotein binding Inferred from physical interaction Ref.18. Source: UniProtKB polynucleotide 3'-phosphatase activity Inferred from direct assay. Source: UniProtKB protein N-terminus binding Inferred from physical interaction Ref.14. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PARP1	P09874	7	EBI-847814,EBI-355676
XRCC1	P18887	8	EBI-847814,EBI-947466

Alternative products

This entry describes 10 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z2E3-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: Major form.

Isoform 2 (identifier: Q7Z2E3-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-188: Missing.

Note: Minor form.

Isoform 3 (identifier: Q7Z2E3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     104-175: Missing.

Note: May be an aberrant isoform present in cancer cell lines.

Isoform 4 (identifier: Q7Z2E3-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-102: Missing.

Note: May be an aberrant isoform present in cancer cell lines.

Isoform 5 (identifier: Q7Z2E3-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
     59-112: Missing.

Note: May be an aberrant isoform present in cancer cell lines.

Isoform 6 (identifier: Q7Z2E3-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-193: Missing.
     306-356: AVIEMVQEAGRVTVRDGMPELLKLPLRCHECQQLLPSIPQLKEHLRKHWTQ → E

Note: May be an aberrant isoform present in cancer cell lines.

Isoform 7 (identifier: Q7Z2E3-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.

Isoform 8 (identifier: Q7Z2E3-8)

The sequence of this isoform differs from the canonical sequence as follows:
     175-193: Missing.

Note: May be an aberrant isoform present in cancer cell lines.

Isoform 9 (identifier: Q7Z2E3-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: Missing.
     306-356: AVIEMVQEAGRVTVRDGMPELLKLPLRCHECQQLLPSIPQLKEHLRKHWTQ → E

Note: No experimental confirmation available.

Isoform 10 (identifier: Q7Z2E3-10)

The sequence of this isoform differs from the canonical sequence as follows:
     59-112: Missing.

Note: May be an aberrant isoform present in cancer cell lines.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 356

356

Aprataxin

PRO_0000109838

Regions

Domain

38 – 87

50

FHA-like

Domain

182 – 287

106

HIT

Zinc finger

331 – 353

23

C2H2-type

Region

1 – 110

110

Interactions with ADPRT and NCL

Motif

126 – 131

6

Nuclear localization signal Probable

Motif

272 – 276

5

Histidine triad motif

Sites

Active site

274

1

Tele-AMP-histidine intermediate Probable

Natural variations

Alternative sequence

1 – 193

193

Missing in isoform 6.

VSP_010534

Alternative sequence

1 – 188

188

Missing in isoform 2.

VSP_010535

Alternative sequence

1 – 102

102

Missing in isoform 4.

VSP_010536

Alternative sequence

1 – 14

14

Missing in isoform 5, isoform 7 and isoform 9.

VSP_010537

Alternative sequence

59 – 112

54

Missing in isoform 5 and isoform 10.

VSP_010538

Alternative sequence

104 – 175

72

Missing in isoform 3.

VSP_010539

Alternative sequence

175 – 193

19

Missing in isoform 8.

VSP_010540

Alternative sequence

306 – 356

51

AVIEM…KHWTQ → E in isoform 6 and isoform 9.

VSP_010541

Natural variant

211

1

K → Q in AOA; it probably does not greatly affect the protein; heterozygous. Ref.20

VAR_018794

Natural variant

212

1

A → V in AOA; heterozygous. Ref.21

VAR_018795

Natural variant

213

1

R → H in AOA. Ref.10

VAR_018796

Natural variant

215

1

H → R in AOA. Ref.19

VAR_018797

Natural variant

220

1

P → L in AOA. Ref.9 Ref.10

VAR_018798

Natural variant

237

1

L → P in AOA. Ref.22

VAR_025365

Natural variant

277

1

V → G in AOA; abolishes DNA-binding and enzymatic activity towards Ap(4)A. Ref.9 Ref.15 Ref.21

VAR_018799

Natural variant

281

1

D → G in AOA; heterozygous.

VAR_018800

Natural variant

293

1

W → R in AOA; heterozygous. Ref.21

VAR_018801

Experimental info

Mutagenesis

43

1

R → A: Impairs interaction with XRCC1 and XRCC4. Abolishes localization at sites of DNA double-strand breaks. Loss of interaction with MDC1. Ref.12 Ref.18

Mutagenesis

52

1

K → A: Impairs interaction with MDC1 and localization at sites of DNA double-strand breaks. Ref.18

Mutagenesis

274

1

H → A: Abolishes enzyme activity. Ref.16 Ref.17

Mutagenesis

333

1

C → A: Abolishes DNA-binding and enzyme activity; when associated with A-336. Ref.17

Mutagenesis

336

1

C → A: Abolishes DNA-binding and enzyme activity; when associated with A-333. Ref.17

Secondary structure

1

.

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356

Helix Strand Turn

Details...

Beta strand

18 – 23

6

Beta strand

30 – 32

3

Beta strand

38 – 41

4

Beta strand

59 – 63

5

Beta strand

70 – 74

5

Beta strand

92 – 95

4

Beta strand

101 – 104

4

Beta strand

107 – 115

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified June 7, 2004. Version 2. Checksum: 5B338490E35EC8E4	FASTA	356	40,740
	10 20 30 40 50 60 MSNVNLSVSD FWRVMMRVCW LVRQDSRHQR IRLPHLEAVV IGRGPETKIT DKKCSRQQVQ 70 80 90 100 110 120 LKAECNKGYV KVKQVGVNPT SIDSVVIGKD QEVKLQPGQV LHMVNELYPY IVEFEEEAKN 130 140 150 160 170 180 PGLETHRKRK RSGNSDSIER DAAQEAEAGT GLEPGSNSGQ CSVPLKKGKD APIKKESLGH 190 200 210 220 230 240 WSQGLKISMQ DPKMQVYKDE QVVVIKDKYP KARYHWLVLP WTSISSLKAV AREHLELLKH 250 260 270 280 290 300 MHTVGEKVIV DFAGSSKLRF RLGYHAIPSM SHVHLHVISQ DFDSPCLKNK KHWNSFNTEY 310 320 330 340 350 FLESQAVIEM VQEAGRVTVR DGMPELLKLP LRCHECQQLL PSIPQLKEHL RKHWTQ
	Isoform 2 (Short) [UniParc]. Checksum: 2AF4F98B97C0A76B	FASTA	168	19,715
	10 20 30 40 50 60 MQDPKMQVYK DEQVVVIKDK YPKARYHWLV LPWTSISSLK AVAREHLELL KHMHTVGEKV 70 80 90 100 110 120 IVDFAGSSKL RFRLGYHAIP SMSHVHLHVI SQDFDSPCLK NKKHWNSFNT EYFLESQAVI 130 140 150 160 EMVQEAGRVT VRDGMPELLK LPLRCHECQQ LLPSIPQLKE HLRKHWTQ
	Isoform 3 [UniParc]. Checksum: 4213615369B997A5	FASTA	284	32,901
	10 20 30 40 50 60 MSNVNLSVSD FWRVMMRVCW LVRQDSRHQR IRLPHLEAVV IGRGPETKIT DKKCSRQQVQ 70 80 90 100 110 120 LKAECNKGYV KVKQVGVNPT SIDSVVIGKD QEVKLQPGQV LHMESLGHWS QGLKISMQDP 130 140 150 160 170 180 KMQVYKDEQV VVIKDKYPKA RYHWLVLPWT SISSLKAVAR EHLELLKHMH TVGEKVIVDF 190 200 210 220 230 240 AGSSKLRFRL GYHAIPSMSH VHLHVISQDF DSPCLKNKKH WNSFNTEYFL ESQAVIEMVQ 250 260 270 280 EAGRVTVRDG MPELLKLPLR CHECQQLLPS IPQLKEHLRK HWTQ
	Isoform 4 [UniParc]. Checksum: B2338C3B2822B710	FASTA	254	29,108
	10 20 30 40 50 60 MVNELYPYIV EFEEEAKNPG LETHRKRKRS GNSDSIERDA AQEAEAGTGL EPGSNSGQCS 70 80 90 100 110 120 VPLKKGKDAP IKKESLGHWS QGLKISMQDP KMQVYKDEQV VVIKDKYPKA RYHWLVLPWT 130 140 150 160 170 180 SISSLKAVAR EHLELLKHMH TVGEKVIVDF AGSSKLRFRL GYHAIPSMSH VHLHVISQDF 190 200 210 220 230 240 DSPCLKNKKH WNSFNTEYFL ESQAVIEMVQ EAGRVTVRDG MPELLKLPLR CHECQQLLPS 250 IPQLKEHLRK HWTQ
	Isoform 5 [UniParc]. Checksum: AD5D2BD20A81EBD6	FASTA	288	33,125
	10 20 30 40 50 60 MMRVCWLVRQ DSRHQRIRLP HLEAVVIGRG PETKITDKKC SRQQEFEEEA KNPGLETHRK 70 80 90 100 110 120 RKRSGNSDSI ERDAAQEAEA GTGLEPGSNS GQCSVPLKKG KDAPIKKESL GHWSQGLKIS 130 140 150 160 170 180 MQDPKMQVYK DEQVVVIKDK YPKARYHWLV LPWTSISSLK AVAREHLELL KHMHTVGEKV 190 200 210 220 230 240 IVDFAGSSKL RFRLGYHAIP SMSHVHLHVI SQDFDSPCLK NKKHWNSFNT EYFLESQAVI 250 260 270 280 EMVQEAGRVT VRDGMPELLK LPLRCHECQQ LLPSIPQLKE HLRKHWTQ
	Isoform 6 [UniParc]. Checksum: 5583AA4F55EDF41B	FASTA	113	13,305
	10 20 30 40 50 60 MQVYKDEQVV VIKDKYPKAR YHWLVLPWTS ISSLKAVARE HLELLKHMHT VGEKVIVDFA 70 80 90 100 110 GSSKLRFRLG YHAIPSMSHV HLHVISQDFD SPCLKNKKHW NSFNTEYFLE SQE
	Isoform 7 [UniParc]. Checksum: C0D4FAEBF89ABA74	FASTA	342	39,104
	10 20 30 40 50 60 MMRVCWLVRQ DSRHQRIRLP HLEAVVIGRG PETKITDKKC SRQQVQLKAE CNKGYVKVKQ 70 80 90 100 110 120 VGVNPTSIDS VVIGKDQEVK LQPGQVLHMV NELYPYIVEF EEEAKNPGLE THRKRKRSGN 130 140 150 160 170 180 SDSIERDAAQ EAEAGTGLEP GSNSGQCSVP LKKGKDAPIK KESLGHWSQG LKISMQDPKM 190 200 210 220 230 240 QVYKDEQVVV IKDKYPKARY HWLVLPWTSI SSLKAVAREH LELLKHMHTV GEKVIVDFAG 250 260 270 280 290 300 SSKLRFRLGY HAIPSMSHVH LHVISQDFDS PCLKNKKHWN SFNTEYFLES QAVIEMVQEA 310 320 330 340 GRVTVRDGMP ELLKLPLRCH ECQQLLPSIP QLKEHLRKHW TQ
	Isoform 8 [UniParc]. Checksum: DC2FF196087D3ADB	FASTA	337	38,589
	10 20 30 40 50 60 MSNVNLSVSD FWRVMMRVCW LVRQDSRHQR IRLPHLEAVV IGRGPETKIT DKKCSRQQVQ 70 80 90 100 110 120 LKAECNKGYV KVKQVGVNPT SIDSVVIGKD QEVKLQPGQV LHMVNELYPY IVEFEEEAKN 130 140 150 160 170 180 PGLETHRKRK RSGNSDSIER DAAQEAEAGT GLEPGSNSGQ CSVPLKKGKD APIKMQVYKD 190 200 210 220 230 240 EQVVVIKDKY PKARYHWLVL PWTSISSLKA VAREHLELLK HMHTVGEKVI VDFAGSSKLR 250 260 270 280 290 300 FRLGYHAIPS MSHVHLHVIS QDFDSPCLKN KKHWNSFNTE YFLESQAVIE MVQEAGRVTV 310 320 330 RDGMPELLKL PLRCHECQQL LPSIPQLKEH LRKHWTQ
	Isoform 9 [UniParc]. Checksum: 5802EE9F37B07600	FASTA	292	33,294
	10 20 30 40 50 60 MMRVCWLVRQ DSRHQRIRLP HLEAVVIGRG PETKITDKKC SRQQVQLKAE CNKGYVKVKQ 70 80 90 100 110 120 VGVNPTSIDS VVIGKDQEVK LQPGQVLHMV NELYPYIVEF EEEAKNPGLE THRKRKRSGN 130 140 150 160 170 180 SDSIERDAAQ EAEAGTGLEP GSNSGQCSVP LKKGKDAPIK KESLGHWSQG LKISMQDPKM 190 200 210 220 230 240 QVYKDEQVVV IKDKYPKARY HWLVLPWTSI SSLKAVAREH LELLKHMHTV GEKVIVDFAG 250 260 270 280 290 SSKLRFRLGY HAIPSMSHVH LHVISQDFDS PCLKNKKHWN SFNTEYFLES QE
	Isoform 10 [UniParc]. Checksum: 4CAFA4C9BB2399EC	FASTA	302	34,761
	10 20 30 40 50 60 MSNVNLSVSD FWRVMMRVCW LVRQDSRHQR IRLPHLEAVV IGRGPETKIT DKKCSRQQEF 70 80 90 100 110 120 EEEAKNPGLE THRKRKRSGN SDSIERDAAQ EAEAGTGLEP GSNSGQCSVP LKKGKDAPIK 130 140 150 160 170 180 KESLGHWSQG LKISMQDPKM QVYKDEQVVV IKDKYPKARY HWLVLPWTSI SSLKAVAREH 190 200 210 220 230 240 LELLKHMHTV GEKVIVDFAG SSKLRFRLGY HAIPSMSHVH LHVISQDFDS PCLKNKKHWN 250 260 270 280 290 300 SFNTEYFLES QAVIEMVQEA GRVTVRDGMP ELLKLPLRCH ECQQLLPSIP QLKEHLRKHW TQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of FHA-HIT as a novel nuclear protein involved in cell-cycle regulation." Huang C.-H. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	Chen Y., Huang C.-H. Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8 AND 10). Tissue: Hypothalamus, Kidney, Lung adenocarcinoma, Lymphoma, Melanoma, Muscle, Retinoblastoma, Skin and Testis.
[3]	"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 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Colon.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9). Tissue: Endometrium.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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. , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4). Tissue: Lung and Lymph.
[8]	"Mutations in the APTX gene." Hellenbroich Y., Habeck M. Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-261 (ISOFORMS 2; 4; 5 AND 7). Tissue: Brain.
[9]	"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. 29:184-188(2001) [PubMed: 11586299] [Abstract] Cited for: TISSUE SPECIFICITY, VARIANTS AOA LEU-220 AND GLY-277.
[10]	"The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin." Moreira M.-C., 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. 29:189-193(2001) [PubMed: 11586300] [Abstract] Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY, VARIANTS AOA HIS-213 AND LEU-220.
[11]	"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. 55:241-249(2004) [PubMed: 14755728] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH XRCC1.
[12]	"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 P.M., Breslin C., Deeks E.D., Byrd P.J., Ju L., Bieganowski P., Brenner C., Moreira M.-C., Taylor A.M.R., Caldecott K.W. DNA Repair 3:1493-1502(2004) [PubMed: 15380105] [Abstract] Cited for: INTERACTION WITH XRCC1 AND XRCC4, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-43.
[13]	"Aprataxin, a novel protein that protects against genotoxic stress." Gueven N., Becherel O.J., Kijas A.W., Chen P., Howe O., Rudolph J.H., Gatti R., Date H., Onodera O., Taucher-Scholz G., Lavin M.F. Hum. Mol. Genet. 13:1081-1093(2004) [PubMed: 15044383] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH XRCC1; ADPRT; TP53 AND NCL.
[14]	"Nucleolar localization of aprataxin is dependent on interaction with nucleolin and on active ribosomal DNA transcription." Becherel O.J., Gueven N., Birrell G.W., Schreiber V., Suraweera A., Jakob B., Taucher-Scholz G., Lavin M.F. Hum. Mol. Genet. 15:2239-2249(2006) [PubMed: 16777843] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH XRCC1 AND NCL.
[15]	"Aprataxin forms a discrete branch in the HIT (histidine triad) superfamily of proteins with both DNA/RNA binding and nucleotide hydrolase activities." Kijas A.W., Harris J.L., Harris J.M., Lavin M.F. J. Biol. Chem. 281:13939-13948(2006) [PubMed: 16547001] [Abstract] Cited for: FUNCTION, DNA-BINDING, CHARACTERIZATION OF VARIANT GLY-277.
[16]	"The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates." Ahel I., Rass U., El-Khamisy S.F., Katyal S., Clements P.M., McKinnon P.J., Caldecott K.W., West S.C. Nature 443:713-716(2006) [PubMed: 16964241] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF HIS-274.
[17]	"Actions of aprataxin in multiple DNA repair pathways." Rass U., Ahel I., West S.C. J. Biol. Chem. 282:9469-9474(2007) [PubMed: 17276982] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF HIS-274; CYS-333 AND CYS-336.
[18]	"CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response." Becherel O.J., Jakob B., Cherry A.L., Gueven N., Fusser M., Kijas A.W., Peng C., Katyal S., McKinnon P.J., Chen J., Epe B., Smerdon S.J., Taucher-Scholz G., Lavin M.F. Nucleic Acids Res. 38:1489-1503(2010) [PubMed: 20008512] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 15-116, SUBCELLULAR LOCATION, INTERACTION WITH MDC1, MUTAGENESIS OF ARG-43 AND LYS-52.
[19]	"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 59:590-595(2002) [PubMed: 12196655] [Abstract] Cited for: VARIANT AOA ARG-215.
[20]	"Phenotypic variability of aprataxin gene mutations." Tranchant C., Fleury M., Moreira M.-C., Koenig M., Warter J.-M. Neurology 60:868-870(2003) [PubMed: 12629250] [Abstract] Cited for: VARIANT AOA GLN-211.
[21]	"Cerebellar ataxia with oculomotor apRAxia type 1: clinical and genetic studies." Le Ber I., Moreira M.-C., Rivaud-Pechoux S., Chamayou C., Ochsner F., Kuntzer T., Tardieu M., Saied G., Habert M.-O., Demarquay G., Tannier C., Beis J.-M., Brice A., Koenig M., Duerr A. Brain 126:2761-2772(2003) [PubMed: 14506070] [Abstract] Cited for: VARIANTS AOA VAL-212; GLY-277 AND ARG-293.
[22]	"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. 57:777-777(2005) [PubMed: 15852392] [Abstract] Cited for: VARIANT AOA PRO-237.
[23]	"Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation." Quinzii C.M., Kattah A.G., Naini A., Akman H.O., Mootha V.K., DiMauro S., Hirano M. Neurology 64:539-541(2005) [PubMed: 15699391] [Abstract] Cited for: INVOLVEMENT IN COENZYME Q10 DEFICIENCY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY040777 mRNA. Translation: AAK91768.1.
AY208829 mRNA. Translation: AAP86319.1.
AY208830 mRNA. Translation: AAP86320.1.
AY208831 mRNA. Translation: AAP86321.1.
AY208832 mRNA. Translation: AAP86322.1.
AY208833 mRNA. Translation: AAP86323.1.
AY208834 mRNA. Translation: AAP86324.1.
AY208835 mRNA. Translation: AAP86325.1.
AY208836 mRNA. Translation: AAP86326.1.
AY208837 mRNA. Translation: AAP86327.1.
AY208838 mRNA. Translation: AAP86328.1.
AY208839 mRNA. Translation: AAP86329.1.
AY208840 mRNA. Translation: AAP86330.1.
AY208841 mRNA. Translation: AAP86331.1.
AY208842 mRNA. Translation: AAP86332.1.
AK000164 mRNA. Translation: BAA90985.1.
BX538161 mRNA. Translation: CAD98041.1.
AL162590, AL353717 Genomic DNA. Translation: CAI15549.1.
AL353717, AL162590 Genomic DNA. Translation: CAI15728.1.
AL353717 Genomic DNA. Translation: CAI15734.1.
CH471071 Genomic DNA. Translation: EAW58530.1.
CH471071 Genomic DNA. Translation: EAW58529.1.
CH471071 Genomic DNA. Translation: EAW58531.1.
CH471071 Genomic DNA. Translation: EAW58534.1.
CH471071 Genomic DNA. Translation: EAW58535.1.
BC001628 mRNA. Translation: AAH01628.1.
BC032650 mRNA. Translation: AAH32650.1.
AJ565850 mRNA. Translation: CAD92454.1.
AJ565851 mRNA. Translation: CAD92455.1.
AJ565852 mRNA. Translation: CAD92456.1.
AJ565853 mRNA. Translation: CAD92457.1.
AJ565854 mRNA. Translation: CAD92458.1.
AJ565855 mRNA. Translation: CAD92459.1.
AJ575566 mRNA. Translation: CAE01427.1.

IPI

IPI00180685.
IPI00375305.
IPI00411460.
IPI00414767.
IPI00420029.
IPI00420030.
IPI00420031.
IPI00420033.
IPI00554783.
IPI00979014.

RefSeq

NP_001182177.1. NM_001195248.1.
NP_001182178.1. NM_001195249.1.
NP_001182179.1. NM_001195250.1.
NP_001182180.1. NM_001195251.1.
NP_001182181.1. NM_001195252.1.
NP_001182183.1. NM_001195254.1.
NP_778239.1. NM_175069.2.
NP_778243.1. NM_175073.2.

UniGene

Hs.20158.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3KT9	X-ray	1.65	A	15-116	[»]

ProteinModelPortal

Q7Z2E3.

SMR

Q7Z2E3. Positions 15-116, 187-280.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q7Z2E3. 16 interactions.

MINT

MINT-1205251.

STRING

Q7Z2E3.

PTM databases

PhosphoSite

Q7Z2E3.

Polymorphism databases

DMDM

48428038.

Proteomic databases

PRIDE

Q7Z2E3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379819; ENSP00000369147; ENSG00000137074.

GeneID

54840.

KEGG

hsa:54840.

UCSC

uc003zrj.1. human.
uc003zrm.1. human.
uc003zrv.1. human.

Organism-specific databases

CTD

54840.

GeneCards

GC09M032962.

HGNC

HGNC:15984. APTX.

MIM

208920. phenotype.
606350. gene.
607426. phenotype.

neXtProt

NX_Q7Z2E3.

Orphanet

1168. Ataxia - oculomotor apraxia type 1.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00570000079163.

HOVERGEN

HBG050555.

InParanoid

Q7Z2E3.

OMA

MSHVHLH.

PhylomeDB

Q7Z2E3.

Gene expression databases

ArrayExpress

Q7Z2E3.

Bgee

Q7Z2E3.

CleanEx

HS_APTX.

Genevestigator

Q7Z2E3.

GermOnline

ENSG00000137074. Homo sapiens.

Family and domain databases

InterPro

IPR000253. FHA_dom.
IPR011146. His_triad-like_motif.
IPR011151. His_triad_motif.
IPR019808. Histidine_triad_CS.
IPR001310. Histidine_triad_HIT.
IPR008984. SMAD_FHA_domain.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
[Graphical view]

Gene3D

G3DSA:2.60.200.20. FHA. 1 hit.
G3DSA:3.30.428.10. His_triad_motif. 1 hit.

KO

K10863.

SMART

SM00355. ZnF_C2H2. 1 hit.
[Graphical view]

SUPFAM

SSF54197. His_triad-like_motif. 1 hit.
SSF49879. SMAD_FHA. 1 hit.

PROSITE

PS00892. HIT_1. 1 hit.
PS51084. HIT_2. 1 hit.
PS00028. ZINC_FINGER_C2H2_1. 1 hit.
PS50157. ZINC_FINGER_C2H2_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

57644.

SOURCE

Search...

Entry information

Entry name

APTX_HUMAN

Accession

Primary (citable) accession number: Q7Z2E3
Secondary accession number(s): A8MTN4 , D3DRK9, D3DRL0, Q0P662, Q5T781, Q5T784, Q7Z2F3, Q7Z336, Q7Z5R5, Q7Z6V7, Q7Z6V8, Q9NXM5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	June 7, 2004
Last modified:	December 14, 2011
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.