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Description:
DNA polymerase eta (EC 2.7.7.7) (RAD30 homolog A) (Xerodermapigmentosum variant type protein).
Molecular weight: 78413
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) regulation of DNA repair( GO:0006282 )
Important dates:
15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
01-NOV-1999, sequence version 1.
07-FEB-2006, entry version 30.
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 POLH_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | AB024313 | BAA81666.1 | - |
| EMBL | AF158185 | AAD43810.1 | - |
| EMBL | AB038008 | BAB18601.1 | - |
| EMBL | AY388614 | AAQ81300.1 | - |
| EMBL | AL353602 | CAI12786.1 | - |
| EMBL | AL355802 | CAI12786.1 | JOINED |
| EMBL | AL353602 | CAI12787.1 | - |
| EMBL | AL355802 | CAI12787.1 | JOINED |
| EMBL | AL355802 | CAI42641.1 | - |
| EMBL | AL353602 | CAI42641.1 | JOINED |
| EMBL | AL355802 | CAI42642.1 | - |
| EMBL | AL353602 | CAI42642.1 | JOINED |
| EMBL | BC015742 | AAH15742.1 | - |
| HSSP | P96022 | 1K1S | |
| Ensembl | ENSG00000170734 | Homo sapiens.1 | |
| HGNC | HGNC:9181 | POLH.1 | |
| MIM | 278750 | phenotype. | |
| MIM | 603968 | gene. | |
| Reactome | Q9Y253 | -.1 | |
| GO | GO:0005654 | C:nucleoplasm | TAS. |
| GO | GO:0003684 | F:damaged DNA binding | TAS. |
| GO | GO:0015999 | F:eta DNA polymerase activity | TAS. |
| GO | GO:0006282 | P:regulation of DNA repair | TAS. |
| InterPro | IPR001126 | UMUC_like. | |
| Pfam | PF00817 | IMS | 1. |
| PROSITE | PS50173 | UMUC | 1. |
Keywords:
Alternative splicing; Direct protein sequencing; Disease mutation; DNA damage; DNA repair; DNA replication; DNA synthesis; DNA-binding; DNA-directed DNA polymerase; Magnesium; Metal-binding; Mutator protein; Nuclear protein; Nucleotidyltransferase; Polymorphism; Schiff base; Transferase; Xeroderma pigmentosum.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 132-163;
RP 395-404; 429-450 AND 495-511, FUNCTION, INVOLVEMENT IN XPV, AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Cervix carcinoma;
RX MEDLINE=99311850; PubMed=10385124; DOI=10.1038/21447;
RA Masutani C., Kusumoto R., Yamada A., Dohmae N., Yokoi M., Yuasa M.,
RA Araki M., Iwai S., Takio K., Hanaoka F.;
RT "The XPV (Xeroderma pigmentosum variant) gene encodes human DNA
RT polymerase eta.";
RL Nature 399:700-704(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT XPV LEU-75 DEL.
RX MEDLINE=99329344; PubMed=10398605; DOI=10.1126/science.285.5425.263;
RA Johnson R.E., Kondratick C.M., Prakash S., Prakash L.;
RT "hRAD30 mutations in the variant form of xeroderma pigmentosum.";
RL Science 285:263-265(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN XPV.
RX PubMed=11032022; DOI=10.1038/sj.onc.1203842;
RA Yuasa M., Masutani C., Eki T., Hanaoka F.;
RT "Genomic structure, chromosomal localization and identification of
RT mutations in the xeroderma pigmentosum variant (XPV) gene.";
RL Oncogene 19:4721-4728(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-209; TRP-334;
RP MET-478; PRO-584; VAL-595 AND LEU-647.
RA Rieder M.J., Livingston R.J., Daniels M.R., Montoya M.A., Chung M.-W.,
RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX MEDLINE=22935763; PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Skin;
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 FUNCTION, AND MUTAGENESIS.
RX PubMed=11743006; DOI=10.1093/emboj/20.24.7303;
RA Glick E., Vigna K.L., Loeb L.A.;
RT "Mutations in human DNA polymerase eta motif II alter bypass of DNA
RT lesions.";
RL EMBO J. 20:7303-7312(2001).
RN [8]
RP FUNCTION.
RX PubMed=11376341; DOI=10.1038/88740;
RA Zeng X., Winter D.B., Kasmer C., Kraemer K.H., Lehmann A.R.,
RA Gearhart P.J.;
RT "DNA polymerase eta is an A-T mutator in somatic hypermutation of
RT immunoglobulin variable genes.";
RL Nat. Immunol. 2:537-541(2001).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH POLI.
RX PubMed=12606586; DOI=10.1093/emboj/cdf618;
RA Kannouche P.L., Fernandez de Henestrosa A.R., Coull B., Vidal A.E.,
RA Gray C., Zicha D., Woodgate R., Lehmann A.R.;
RT "Localization of DNA polymerases eta and iota to the replication
RT machinery is tightly co-ordinated in human cells.";
RL EMBO J. 22:1223-1233(2003).
RN [10]
RP FUNCTION, AND SCHIFF BASE FORMATION.
RX PubMed=14630940; DOI=10.1101/gad.1146103;
RA Haracska L., Prakash L., Prakash S.;
RT "A mechanism for the exclusion of low-fidelity human Y-family DNA
RT polymerases from base excision repair.";
RL Genes Dev. 17:2777-2785(2003).
RN [11]
RP MUTAGENESIS OF TYR-52.
RX PubMed=12644469; DOI=10.1074/jbc.M300686200;
RA Glick E., Chau J.S., Vigna K.L., McCulloch S.D., Adman E.T.,
RA Kunkel T.A., Loeb L.A.;
RT "Amino acid substitutions at conserved tyrosine 52 alter fidelity and
RT bypass efficiency of human DNA polymerase eta.";
RL J. Biol. Chem. 278:19341-19346(2003).
RN [12]
RP FUNCTION.
RX PubMed=14734526; DOI=10.1084/jem.20031831;
RA Faili A., Aoufouchi S., Weller S., Vuillier F., Stary A., Sarasin A.,
RA Reynaud C.-A., Weill J.-C.;
RT "DNA polymerase eta is involved in hypermutation occurring during
RT immunoglobulin class switch recombination.";
RL J. Exp. Med. 199:265-270(2004).
RN [13]
RP INTERACTION WITH MONOUBIQUITINATED PCNA.
RX PubMed=15149598; DOI=10.1016/S1097-2765(04)00259-X;
RA Kannouche P.L., Wing J., Lehmann A.R.;
RT "Interaction of human DNA polymerase eta with monoubiquitinated PCNA:
RT a possible mechanism for the polymerase switch in response to DNA
RT damage.";
RL Mol. Cell 14:491-500(2004).
RN [14]
RP VARIANTS XPV GLU-535 AND THR-589.
RX PubMed=11121129; DOI=10.1046/j.1523-1747.2000.00154.x;
RA Itoh T., Linn S., Kamide R., Tokushige H., Katori N., Hosaka Y.,
RA Yamaizumi M.;
RT "Xeroderma pigmentosum variant heterozygotes show reduced levels of
RT recovery of replicative DNA synthesis in the presence of caffeine
RT after ultraviolet irradiation.";
RL J. Invest. Dermatol. 115:981-985(2000).
RN [15]
RP VARIANTS XPV LEU-75 DEL; HIS-111 PRO-122; VAL-263 AND SER-361.
RX PubMed=11773631; DOI=10.1073/pnas.022473899;
RA Broughton B.C., Cordonnier A., Kleijer W.J., Jaspers N.G., Fawcett H.,
RA Raams A., Garritsen V.H., Stary A., Avril M.-F., Boudsocq F.,
RA Masutani C., Hanaoka F., Fuchs R.P.P., Sarasin A., Lehmann A.R.;
RT "Molecular analysis of mutations in DNA polymerase eta in xeroderma
RT pigmentosum variant patients.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:815-820(2002).
Feature:
CHAIN 1 713 DNA polymerase eta.
/FTId=PRO_0000173986.
DOMAIN 9 259 UmuC.
METAL 13 13 Magnesium (By similarity).
METAL 115 115 Magnesium (By similarity).
VARSPLIC 415 713 Missing (in isoform 2).
/FTId=VSP_012799.
VARIANT 75 75 Missing (in XPV; impairs translesion
synthesis).
/FTId=VAR_021226.
VARIANT 111 111 R -> H (in XPV).
/FTId=VAR_021227.
VARIANT 122 122 T -> P (in XPV).
/FTId=VAR_021228.
VARIANT 209 209 G -> V (in dbSNP:2307456).
/FTId=VAR_021229.
VARIANT 263 263 G -> V (in XPV; impairs translesion
synthesis).
/FTId=VAR_021230.
VARIANT 334 334 R -> W (in dbSNP:9333548).
/FTId=VAR_021231.
VARIANT 361 361 R -> S (in XPV).
/FTId=VAR_021232.
VARIANT 478 478 T -> M (in dbSNP:9296419).
/FTId=VAR_021233.
VARIANT 535 535 K -> E (in XPV).
/FTId=VAR_021234.
VARIANT 584 584 L -> P (in dbSNP:9333554).
/FTId=VAR_021235.
VARIANT 589 589 K -> T (in XPV).
/FTId=VAR_021236.
VARIANT 595 595 M -> V (in dbSNP:9333555).
/FTId=VAR_021237.
VARIANT 647 647 M -> L (in dbSNP:6941583).
/FTId=VAR_021238.
MUTAGEN 52 52 Y->A,F: Reduces DNA polymerase activity.
MUTAGEN 52 52 Y->E: Reduces DNA polymerase activity.
Increases fidelity of replication and
reduces translesion bypass.
Comments:
-!- FUNCTION: DNA polymerase specifically involved in DNA repair.
Plays an important role in translesion synthesis, where the normal
high fidelity DNA polymerases cannot proceed and DNA synthesis
stalls. Plays an important role in the repair of UV-induced
pyrimidine dimers. Depending on the context, it inserts the
correct base, but causes frequent base transitions and
transversions. May play a role in hypermutation at immunoglobulin
genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic
sites, but does not have lyase activity. Targets POLI to
replication foci.
-!- CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) =
diphosphate + DNA(n+1).
-!- COFACTOR: Divalent metal cations. Prefers magnesium, but can also
use manganese.
-!- SUBUNIT: Binds REV1L (By similarity). Binds monoubiquitinated
PCNA, but not unmodified PCNA. Binds POLI.
-!- SUBCELLULAR LOCATION: Nuclear. Accumulates at replication forks
after DNA damage.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q9Y253-1; Sequence=Displayed;
Name=2;
IsoId=Q9Y253-2; Sequence=VSP_012799;
Note=No experimental confirmation available;
-!- DOMAIN: The catalytic core consists of fingers, palm and thumb
subdomains, but the fingers and thumb subdomains are much smaller
than in high-fidelity polymerases; residues from five sequence
motifs of the Y-family cluster around an active site cleft that
can accommodate DNA and nucleotide substrates with relaxed
geometric constraints, with consequently higher rates of
misincorporation and low processivity.
-!- DISEASE: Defects in POLH are the cause of xeroderma pigmentosum
variant type (XPV) [MIM:278750]; also designated as XP-V.
Xeroderma pigmentosum (XP) is an autosomal recessive disease due
to deficient nucleotide excision repair. It is characterized by
hypersensitivity of the skin to sunlight, followed by high
incidence of skin cancer and frequent neurologic abnormalities.
XPV shows normal nucleotide excision repair, but an exaggerated
delay in recovery of replicative DNA synthesis. Most XPV patients
do not develop clinical symptoms and skin neoplasias until a later
age. Clinical manifestations are limited to photo-induced
deterioration of the skin and eyes.
-!- SIMILARITY: Belongs to the DNA polymerase type-Y family.
-!- SIMILARITY: Contains 1 umuC domain.
-!- DATABASE: NAME=Atlas Genet. Cytogenet. Oncol. Haematol.;
WWW="http://www.infobiogen.fr/services/chromcancer/Genes/XPVID303.html".
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Sequence length: 713
MATGQDRVVA LVDMDCFFVQ VEQRQNPHLR NKPCAVVQYK SWKGGGIIAV SYEARAFGVT
RSMWADDAKK LCPDLLLAQV RESRGKANLT KYREASVEVM EIMSRFAVIE RASIDEAYVD
LTSAVQERLQ KLQGQPISAD LLPSTYIEGL PQGPTTAEET VQKEGMRKQG LFQWLDSLQI
DNLTSPDLQL TVGAVIVEEM RAAIERETGF QCSAGISHNK VLAKLACGLN KPNRQTLVSH
GSVPQLFSQM PIRKIRSLGG KLGASVIEIL GIEYMGELTQ FTESQLQSHF GEKNGSWLYA
MCRGIEHDPV KPRQLPKTIG CSKNFPGKTA LATREQVQWW LLQLAQELEE RLTKDRNDND
RVATQLVVSI RVQGDKRLSS LRRCCALTRY DAHKMSHDAF TVIKNCNTSG IQTEWSPPLT
MLFLCATKFS ASAPSSSTDI TSFLSSDPSS LPKVPVTSSE AKTQGSGPAV TATKKATTSL
ESFFQKAAER QKVKEASLSS LTAPTQAPMS NSPSKPSLPF QTSQSTGTEP FFKQKSLLLK
QKQLNNSSVS SPQQNPWSNC KALPNSLPTE YPGCVPVCEG VSKLEESSKA TPAEMDLAHN
SQSMHASSAS KSVLEVTQKA TPNPSLLAAE DQVPCEKCGS LVPVWDMPEH MDYHFALELQ
KSFLQPHSSN PQVVSAVSHQ GKRNPKSPLA CTNKRPRPEG MQTLESFFKP LTH