Reviewed, UniProtKB/Swiss-Prot Q7Z2E3 (APTX_HUMAN)

Names and origin

Protein names

Recommended name:
    Aprataxin
    EC=3.-.-.-
Alternative name(s):
    Forkhead-associated domain histidine triad-like protein
      Short name(s)=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.
Sequence processing	The displayed sequence is not processed.
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-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity.
Subunit structure	Interacts with single-strand break repair proteins XRCC1, XRCC4, ADPRT and p53/TP53. Interacts with NCL.
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. 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. 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.
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-NH(2)

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
Gene Ontology (GO)
Biological process	regulation of protein stability Ref.13 Inferred from mutant phenotype. Source: UniProtKB response to hydrogen peroxide Ref.12 Inferred from direct assay. Source: UniProtKB single strand break repair Inferred from direct assay. Source: UniProtKB
Cellular component	chromatin Ref.12 Inferred from direct assay. Source: UniProtKB nucleolus Ref.12 Ref.13 Inferred from direct assay. Source: UniProtKB nucleoplasm Ref.12 Ref.13 Inferred from direct assay. Source: UniProtKB
Molecular function	DNA 5'-adenosine monophosphate hydrolase activity Ref.14 Ref.15 Ref.16 Inferred from direct assay. Source: UniProtKB chromatin binding Ref.12 Inferred from direct assay. Source: UniProtKB damaged DNA binding Ref.10 Inferred from direct assay. Source: UniProtKB double-stranded DNA binding Ref.14 Ref.16 Inferred from direct assay. Source: UniProtKB double-stranded RNA binding Ref.14 Inferred from direct assay. Source: UniProtKB phosphoglycolate phosphatase activity Inferred from direct assay. Source: UniProtKB protein N-terminus binding Ref.13 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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.

Notes: 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.

Notes: Minor form.

Isoform 3 (identifier: Q7Z2E3-3)

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

Notes: 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.

Notes: 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.

Notes: 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

Notes: 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.

Notes: 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

Notes: No experimental confirmation available.

Isoform 10 (identifier: Q7Z2E3-10)

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

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 356	356	Aprataxin
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.
	Alternative sequence	1 – 188	188	Missing in isoform 2.
	Alternative sequence	1 – 102	102	Missing in isoform 4.
	Alternative sequence	1 – 14	14	Missing in isoform 5, isoform 7 and isoform 9.
	Alternative sequence	59 – 112	54	Missing in isoform 5 and isoform 10.
	Alternative sequence	104 – 175	72	Missing in isoform 3.
	Alternative sequence	175 – 193	19	Missing in isoform 8.
	Alternative sequence	306 – 356	51	AVIEM…KHWTQ → E in isoform 6 and isoform 9.
	Natural variant	211	1	K → Q in AOA; it probably does not greatly affect the protein; heterozygous.
	Natural variant	212	1	A → V in AOA; heterozygous.
	Natural variant	213	1	R → H in AOA.
	Natural variant	215	1	H → R in AOA.
	Natural variant	220	1	P → L in AOA.
	Natural variant	237	1	L → P in AOA.
	Natural variant	277	1	V → G in AOA; abolishes DNA-binding and enzymatic activity towards Ap(4)A.
	Natural variant	281	1	D → G in AOA; heterozygous.
	Natural variant	293	1	W → R in AOA; heterozygous.
Experimental info
	Mutagenesis	43	1	R → A: Impairs interaction with XRCC1 and XRCC4
	Mutagenesis	274	1	H → A: Abolishes enzyme activity
	Mutagenesis	333	1	C → A: Abolishes DNA-binding and enzyme activity; when associated to A-336
	Mutagenesis	336	1	C → A: Abolishes DNA-binding and enzyme activity; when associated to A-333

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		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		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		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		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		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		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		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		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		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 German cDNA consortium Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases 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.,