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Description:
Ataxin-3 (EC 3.4.22.-) (Machado-Joseph disease protein 1)(Spinocerebellar ataxia type 3 protein).
Molecular weight: 43450
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
nucleotide-excision repair (and GO:0045001, a synonym)( GO:0006289 )
Important dates:
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
02-AUG-2002, sequence version 2.
07-MAR-2006, entry version 49.
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 ATX3_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | S75313 | AAB33571.1 | - |
| EMBL | U64820 | AAB63352.1 | - |
| EMBL | U64821 | AAB63353.1 | - |
| EMBL | U64822 | AAB63354.1 | - |
| EMBL | AB050194 | BAB18798.1 | - |
| EMBL | AB038653 | BAB55645.1 | - |
| EMBL | AB038653 | BAB55646.1 | - |
| EMBL | BC033711 | AAH33711.1 | - |
| PDB | 1YZB | NMR | A=1-182. |
| PDB | 2AGA | NMR | A=1-185. |
| HGNC | HGNC:7106 | ATXN3.1 | |
| MIM | 109150 | phenotype. | |
| MIM | 607047 | gene. | |
| LinkHub | P54252 | -.1 | |
| GO | GO:0005737 | C:cytoplasm | TAS. |
| GO | GO:0005654 | C:nucleoplasm | TAS. |
| GO | GO:0007399 | P:neurogenesis | TAS. |
| GO | GO:0006289 | P:nucleotide-excision repair | TAS. |
| GO | GO:0007268 | P:synaptic transmission | TAS. |
| InterPro | IPR006155 | Josephin. | |
| InterPro | IPR003903 | UIM. | |
| Pfam | PF02099 | Josephin | 1. |
| Pfam | PF02809 | UIM | 2. |
| PRINTS | PR01233 | JOSEPHIN. | |
| SMART | SM00726 | UIM | 2. |
| PROSITE | PS50957 | JOSEPHIN | 1. |
| PROSITE | PS50330 | UIM | 2. |
Keywords:
3D-structure; Alternative splicing; Hydrolase; Nuclear protein; Parkinsonism; Phosphorylation; Polymorphism; Repeat; Transcription; Transcription regulation; Triplet repeat expansion.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1), AND VARIANT 361-TYR--LEU-376 DEL.
RC TISSUE=Brain;
RX MEDLINE=95179166; PubMed=7874163;
RA Kawaguchi Y., Okamoto T., Taniwaki M., Aizawa M., Inoue M.,
RA Katayama S., Kawakami H., Nakamura S., Nishimura M., Akiguchi I.,
RA Kimura J., Narumiya S., Kakizuka A.;
RT "CAG expansions in a novel gene for Machado-Joseph disease at
RT chromosome 14q32.1.";
RL Nat. Genet. 8:221-228(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 2), AND VARIANTS VAL-212 AND
RP 361-TYR--LEU-376 DEL.
RX MEDLINE=97418757; PubMed=9274833; DOI=10.1016/S0168-0102(97)00056-4;
RA Goto J., Watanabe M., Ichikawa Y., Yee S.-B., Ihara N., Endo K.,
RA Igarashi S., Takiyama Y., Gaspar C., Maciel P., Tsuji S.,
RA Rouleau G.A., Kanazawa I.;
RT "Machado-Joseph disease gene products carrying different carboxyl
RT termini.";
RL Neurosci. Res. 28:373-377(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 1; 2 AND 3), AND VARIANT
RP 361-TYR--LEU-376 DEL.
RX MEDLINE=21342815; PubMed=11450850; DOI=10.1007/s100380170060;
RA Ichikawa Y., Goto J., Hattori M., Toyoda A., Ishii K., Jeong S.-Y.,
RA Hashida H., Masuda N., Ogata K., Kasai F., Hirai M., Maciel P.,
RA Rouleau G.A., Sakaki Y., Kanazawa I.;
RT "The genomic structure and expression of MJD, the Machado-Joseph
RT disease gene.";
RL J. Hum. Genet. 46:413-422(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP VAL-212.
RC TISSUE=Mammary gland;
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 [5]
RP SUBCELLULAR LOCATION.
RX MEDLINE=98248424; PubMed=9580663; DOI=10.1093/hmg/7.6.991;
RA Tait D., Riccio M., Sittler A., Scherzinger E., Santi S., Ognibene A.,
RA Maraldi N.M., Lehrach H., Wanker E.E.;
RT "Ataxin-3 is transported into the nucleus and associates with the
RT nuclear matrix.";
RL Hum. Mol. Genet. 7:991-997(1998).
RN [6]
RP FUNCTION.
RX MEDLINE=22323318; PubMed=12297501; DOI=10.1074/jbc.M205259200;
RA Li F., Macfarlan T., Pittman R.N., Chakravarti D.;
RT "Ataxin-3 is a histone-binding protein with two independent
RT transcriptional corepressor activities.";
RL J. Biol. Chem. 277:45004-45012(2002).
RN [7]
RP 3D-STRUCTURE MODELING.
RX MEDLINE=22374627; PubMed=12486728; DOI=10.1002/prot.10280;
RA Albrecht M., Hoffmann D., Evert B.O., Schmitt I., Wuellner U.,
RA Lengauer T.;
RT "Structural modeling of ataxin-3 reveals distant homology to
RT adaptins.";
RL Proteins 50:355-370(2003).
RN [8]
RP STRUCTURE BY NMR OF 1-185, FUNCTION, AND MUTAGENESIS OF CYS-14;
RP SER-236; SER-256 AND SER-347.
RX PubMed=16118278; DOI=10.1073/pnas.0506344102;
RA Mao Y., Senic-Matuglia F., Di Fiore P.P., Polo S., Hodsdon M.E.,
RA De Camilli P.;
RT "Deubiquitinating function of ataxin-3: insights from the solution
RT structure of the Josephin domain.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:12700-12705(2005).
Feature:
CHAIN 1 376 Ataxin-3.
/FTId=PRO_0000053831.
DOMAIN 1 180 Josephin.
REPEAT 224 243 UIM 1.
REPEAT 244 263 UIM 2.
REPEAT 343 360 UIM 3.
COMPBIAS 292 317 Poly-Gln.
ACT_SITE 14 14
ACT_SITE 119 119 Probable.
ACT_SITE 134 134 Probable.
MOD_RES 219 219 Phosphoserine (By similarity).
VARSPLIC 10 64 Missing (in isoform 3).
/FTId=VSP_002783.
VARSPLIC 344 376 KACSPFIMFATFTLYLTYELHVIFALHYSSFPL -> DAMS
EEDMLQAAVTMSLETVRNDLKTEGKK (in isoform 2
and isoform 3).
/FTId=VSP_002784.
VARIANT 212 212 M -> V (in dbSNP:1048755).
/FTId=VAR_013688.
VARIANT 306 318 QQQQQQQQQQQQR -> G.
/FTId=VAR_013689.
VARIANT 361 376 Missing (in allele MJD1a).
/FTId=VAR_013690.
MUTAGEN 14 14 C->A: Loss of ubiquitinated protein
retention.
MUTAGEN 236 236 S->A: Inhibits substrate trapping.
MUTAGEN 256 256 S->A: Inhibits substrate trapping.
MUTAGEN 347 347 S->A: No effect on ubiquitination.
CONFLICT 252 252 A -> T (in Ref. 2).
STRAND 3 3
STRAND 11 12
HELIX 14 22
TURN 23 23
STRAND 24 25
HELIX 30 49
TURN 50 50
STRAND 51 51
STRAND 55 55
HELIX 56 62
TURN 63 63
STRAND 64 64
STRAND 66 67
STRAND 70 73
TURN 77 77
HELIX 78 85
TURN 86 88
STRAND 90 96
TURN 97 100
STRAND 101 102
HELIX 106 108
STRAND 109 116
TURN 117 118
STRAND 119 126
TURN 127 128
STRAND 129 134
TURN 135 136
STRAND 138 139
STRAND 141 143
HELIX 145 158
TURN 159 159
STRAND 161 167
HELIX 173 176
STRAND 177 177
STRAND 179 179
TURN 183 184
Comments:
-!- FUNCTION: Interacts with key regulators (CBP, p300 and PCAF) of
transcription and represses transcription. Acts as a histone-
binding protein that regulates transcription. Acts as a
deubiquitinating enzyme.
-!- SUBUNIT: Interacts with DNA repair proteins RAD23A and RAD23B.
-!- SUBCELLULAR LOCATION: Predominantly nuclear, but not exclusively;
inner nuclear matrix.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=P54252-1; Sequence=Displayed;
Name=2;
IsoId=P54252-2; Sequence=VSP_002784;
Name=3;
IsoId=P54252-3; Sequence=VSP_002783, VSP_002784;
-!- TISSUE SPECIFICITY: Ubiquitous.
-!- POLYMORPHISM: The poly-Gln region of ATXN3 is highly polymorphic
(14 to 41 repeats) in the normal population and is expanded to
about 55-82 repeats in MJD patients. Longer expansions result in
earlier onset and more severe clinical manifestations of the
disease.
-!- POLYMORPHISM: The MJD1a allele carries a single nucleotide
substition in codon 349 generating a stop codon instead of a Tyr.
In the Japanese population, the MJD1a allele seems to be
significantly associated with Gln expansion.
-!- DISEASE: Defects in ATXN3 are the cause of Machado-Joseph disease
(MJD) [MIM:109150]; also known as spinorerebellar ataxia 3 (SCA3).
MJD is a neurodegenerative disorder characterized by cerebellar
ataxia, pyramidal and extrapyramidal signs, parkinsonism,
peripheral nerve palsy, external ophtalmoplegia, facial and
lingual fasciculation and bulging. This disease is autosomal
dominant, with a late onset of symptoms, generally after the
fourth decade.
-!- SIMILARITY: Contains 1 Josephin domain.
-!- SIMILARITY: Contains 3 UIM (ubiquitin-interacting motif) repeats.
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Sequence length: 376
MESIFHEKQE GSLCAQHCLN NLLQGEYFSP VELSSIAHQL DEEERMRMAE GGVTSEDYRT
FLQQPSGNMD DSGFFSIQVI SNALKVWGLE LILFNSPEYQ RLRIDPINER SFICNYKEHW
FTVRKLGKQW FNLNSLLTGP ELISDTYLAL FLAQLQQEGY SIFVVKGDLP DCEADQLLQM
IRVQQMHRPK LIGEELAQLK EQRVHKTDLE RMLEANDGSG MLDEDEEDLQ RALALSRQEI
DMEDEEADLR RAIQLSMQGS SRNISQDMTQ TSGTNLTSEE LRKRREAYFE KQQQKQQQQQ
QQQQQQQQQQ QQQQQQQRDL SGQSSHPCER PATSSGALGS DLGKACSPFI MFATFTLYLT
YELHVIFALH YSSFPL