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Description:
DNA polymerase kappa (EC 2.7.7.7) (DINB protein) (DINP).
Molecular weight: 98809
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 )
Important dates:
15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
07-MAR-2006, entry version 29.
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 POLK_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | AB027564 | BAA86943.1 | - |
| EMBL | AF163570 | AAF02540.1 | - |
| EMBL | AF194973 | AAF23270.1 | - |
| EMBL | AF315602 | AAN15780.1 | - |
| EMBL | AF318313 | AAN15781.1 | - |
| EMBL | AY273797 | AAP12648.1 | - |
| EMBL | AK091659 | BAC03714.1 | - |
| EMBL | BC014955 | AAH14955.1 | - |
| EMBL | BC050718 | AAH50718.1 | - |
| EMBL | AB036934 | BAB58975.1 | - |
| EMBL | AB036935 | BAB58976.1 | - |
| PDB | 1T94 | X-ray | A/B=68-526. |
| Ensembl | ENSG00000122008 | Homo sapiens.1 | |
| HGNC | HGNC:9183 | POLK.1 | |
| MIM | 605650 | gene. | |
| GO | GO:0006280 | P:mutagenesis | TAS. |
| InterPro | IPR001126 | UMUC_like. | |
| InterPro | IPR006642 | Znf_Rad18_put. | |
| Pfam | PF00817 | IMS | 1. |
| SMART | SM00734 | ZnF_Rad18 | 2. |
| PROSITE | PS50173 | UMUC | 1. |
Keywords:
3D-structure; Alternative splicing; DNA damage; DNA repair; DNA replication; DNA synthesis; DNA-binding; DNA-directed DNA polymerase; Magnesium; Metal-binding; Mutator protein; Nuclear protein; Nucleotidyltransferase; Polymorphism; Repeat; Schiff base; Transferase; Zinc; Zinc-finger.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Testis;
RX MEDLINE=20087452; PubMed=10620008;
RA Ogi T., Kato T. Jr., Kato R., Ohmori H.;
RT "Mutation enhancement by DINB1, a mammalian homologue of the
RT Escherichia coli mutagenesis protein dinB.";
RL Genes Cells 4:607-618(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Cervix carcinoma;
RX MEDLINE=99449784; PubMed=10518552; DOI=10.1073/pnas.96.21.11922;
RA Gerlach V.L., Aravind L., Gotway G., Schultz R.A., Koonin E.V.,
RA Friedberg E.C.;
RT "Human and mouse homologs of Escherichia coli DinB (DNA polymerase
RT IV), members of the UmuC/DinB superfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:11922-11927(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Poltoratsky V.P., Scharff M.D.;
RT "Homo sapiens DINP protein mRNA, complete cds.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Revert-Ros F., Saus J.;
RT "A bidirectional promoter for the genes encoding DNA polymerase kappa
RT and Goodpasture autoantigen binding protein: identification of a novel
RT pol kappa alternative spliced variant.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-595 AND ASN-832.
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 (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-313 (ISOFORMS 1 AND 2).
RC TISSUE=Lymph, and Spleen;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-231.
RA Ogi T., Yamamoto Y., Ohmori H.;
RT "Homo sapiens genomic sequence, containing DINB1 gene.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP FUNCTION, COFACTOR REQUIREMENT, AND MUTAGENESIS OF ASP-198 AND
RP GLU-199.
RX PubMed=11024016; DOI=10.1074/jbc.M004413200;
RA Gerlach V.L., Feaver W.J., Fischhaber P.L., Friedberg E.C.;
RT "Purification and characterization of pol kappa, a DNA polymerase
RT encoded by the human DINB1 gene.";
RL J. Biol. Chem. 276:92-98(2001).
RN [10]
RP FUNCTION.
RX PubMed=12145297; DOI=10.1074/jbc.M206027200;
RA Fischhaber P.L., Gerlach V.L., Feaver W.J., Hatahet Z., Wallace S.S.,
RA Friedberg E.C.;
RT "Human DNA polymerase kappa bypasses and extends beyond thymine
RT glycols during translesion synthesis in vitro, preferentially
RT incorporating correct nucleotides.";
RL J. Biol. Chem. 277:37604-37611(2002).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=12414988; DOI=10.1242/jcs.00162;
RA Bergoglio V., Bavoux C., Verbiest V., Hoffmann J.-S., Cazaux C.;
RT "Localisation of human DNA polymerase kappa to replication foci.";
RL J. Cell Sci. 115:4413-4418(2002).
RN [12]
RP INTERACTION WITH PCNA.
RX MEDLINE=21644468; PubMed=11784855;
RA Haracska L., Unk I., Johnson R.E., Phillips B.B., Hurwitz J.,
RA Prakash L., Prakash S.;
RT "Stimulation of DNA synthesis activity of human DNA polymerase kappa
RT by PCNA.";
RL Mol. Cell. Biol. 22:784-791(2002).
RN [13]
RP FUNCTION.
RX PubMed=12444249; DOI=10.1073/pnas.252524999;
RA Haracska L., Prakash L., Prakash S.;
RT "Role of human DNA polymerase kappa as an extender in translesion
RT synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16000-16005(2002).
RN [14]
RP FUNCTION.
RX PubMed=12952891; DOI=10.1101/gad.1108603;
RA Wolfle W.T., Washington M.T., Prakash L., Prakash S.;
RT "Human DNA polymerase kappa uses template-primer misalignment as a
RT novel means for extending mispaired termini and for generating single-
RT base deletions.";
RL Genes Dev. 17:2191-2199(2003).
RN [15]
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 [16]
RP FUNCTION.
RX PubMed=15533436; DOI=10.1016/j.jmb.2004.09.064;
RA Yasui M., Suzuki N., Miller H., Matsuda T., Matsui S., Shibutani S.;
RT "Translesion synthesis past 2'-deoxyxanthosine, a nitric oxide-derived
RT DNA adduct, by mammalian DNA polymerases.";
RL J. Mol. Biol. 344:665-674(2004).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 68-526.
RX PubMed=15296733; DOI=10.1016/j.str.2004.05.011;
RA Uljon S.N., Johnson R.E., Edwards T.A., Prakash S., Prakash L.,
RA Aggarwal A.K.;
RT "Crystal structure of the catalytic core of human DNA polymerase
RT kappa.";
RL Structure 12:1395-1404(2004).
Feature:
CHAIN 1 870 DNA polymerase kappa.
/FTId=PRO_0000173990.
DOMAIN 103 358 UmuC.
ZN_FING 621 647 Rad18-type 1.
ZN_FING 776 802 Rad18-type 2.
METAL 107 107 Magnesium (By similarity).
METAL 198 198 Magnesium (By similarity).
METAL 199 199 Magnesium (By similarity).
VARSPLIC 1 90 Missing (in isoform 4).
/FTId=VSP_012804.
VARSPLIC 312 509 Missing (in isoform 3).
/FTId=VSP_012803.
VARSPLIC 453 472 GRTVTIKLKNVNFEVKTRAS -> VLYFDMVSLVFKFFNSK
MLP (in isoform 2).
/FTId=VSP_012801.
VARSPLIC 453 462 GRTVTIKLKN -> KKYLPLLRNC (in isoform 4).
/FTId=VSP_012805.
VARSPLIC 463 870 Missing (in isoform 4).
/FTId=VSP_012806.
VARSPLIC 473 870 Missing (in isoform 2).
/FTId=VSP_012802.
VARIANT 595 595 T -> I (in dbSNP:5744713).
/FTId=VAR_021246.
VARIANT 612 612 I -> V (in dbSNP:3822587).
/FTId=VAR_021247.
VARIANT 832 832 S -> N (in dbSNP:5744716).
/FTId=VAR_021248.
MUTAGEN 198 198 D->A: Loss of DNA polymerase activity;
when associated with A-199.
MUTAGEN 199 199 E->A: Loss of DNA polymerase activity;
when associated with D-198.
CONFLICT 21 21 L -> F (in Ref. 8; BAB58975).
CONFLICT 39 39 I -> T (in Ref. 8; BAB58975).
CONFLICT 219 219 R -> L (in Ref. 8; BAB58976).
CONFLICT 342 342 V -> G (in Ref. 6).
CONFLICT 557 557 K -> N (in Ref. 3).
CONFLICT 847 847 M -> V (in Ref. 3).
TURN 76 77
HELIX 78 94
TURN 95 96
STRAND 100 100
STRAND 103 108
TURN 109 110
HELIX 111 119
HELIX 121 123
TURN 124 125
STRAND 126 126
STRAND 128 131
STRAND 133 134
STRAND 136 139
HELIX 141 145
TURN 146 147
TURN 150 151
HELIX 154 160
TURN 162 163
STRAND 165 167
HELIX 171 188
TURN 190 191
STRAND 193 194
STRAND 196 203
HELIX 205 211
TURN 212 213
HELIX 216 218
STRAND 219 222
HELIX 236 241
STRAND 242 242
TURN 243 248
HELIX 249 251
STRAND 283 285
STRAND 288 289
HELIX 290 305
STRAND 306 306
STRAND 309 316
HELIX 317 326
TURN 327 330
STRAND 332 334
STRAND 337 338
HELIX 339 346
TURN 347 348
STRAND 350 350
HELIX 351 353
TURN 355 356
STRAND 357 357
HELIX 359 367
TURN 368 369
STRAND 372 372
HELIX 373 378
TURN 379 379
HELIX 380 386
STRAND 387 387
HELIX 389 399
TURN 400 401
STRAND 405 405
STRAND 416 425
HELIX 428 439
STRAND 440 441
TURN 442 443
STRAND 454 454
STRAND 456 462
TURN 463 464
STRAND 467 470
HELIX 484 496
STRAND 497 499
TURN 500 501
STRAND 502 502
STRAND 506 513
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. Depending on the context, it inserts the correct base, but
causes frequent base transitions, transversions and frameshifts.
Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base
with 5'-deoxyribose phosphate at abasic sites, but does not have
lyase activity.
-!- CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) =
diphosphate + DNA(n+1).
-!- COFACTOR: Divalent metal cations. Prefers magnesium, but can also
use manganese.
-!- BIOPHYSICOCHEMICAL PROPERTIES:
pH dependence:
Optimum pH is 6.5-7.5;
Temperature dependence:
Optimum temperature is 37 degrees Celsius;
-!- SUBUNIT: Binds REV1L (By similarity). Binds PCNA.
-!- SUBCELLULAR LOCATION: Nuclear. Detected throughout the nucleus and
at replication foci.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Name=1;
IsoId=Q9UBT6-1; Sequence=Displayed;
Name=2;
IsoId=Q9UBT6-2; Sequence=VSP_012801, VSP_012802;
Note=No experimental confirmation available;
Name=3;
IsoId=Q9UBT6-3; Sequence=VSP_012803;
Name=4;
IsoId=Q9UBT6-4; Sequence=VSP_012804, VSP_012805, VSP_012806;
Note=No experimental confirmation available;
-!- TISSUE SPECIFICITY: Detected at low levels in testis, spleen,
prostate and ovary. Detected at very low levels in kidney, colon,
brain, heart, liver, lung, placenta, pancreas and peripheral blood
leukocytes.
-!- 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.
-!- SIMILARITY: Belongs to the DNA polymerase type-Y family.
-!- SIMILARITY: Contains 2 Rad18-type zinc fingers.
-!- SIMILARITY: Contains 1 umuC domain.
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Sequence length: 870
MDSTKEKCDS YKDDLLLRMG LNDNKAGMEG LDKEKINKII MEATKGSRFY GNELKKEKQV
NQRIENMMQQ KAQITSQQLR KAQLQVDRFA MELEQSRNLS NTIVHIDMDA FYAAVEMRDN
PELKDKPIAV GSMSMLSTSN YHARRFGVRA AMPGFIAKRL CPQLIIVPPN FDKYRAVSKE
VKEILADYDP NFMAMSLDEA YLNITKHLEE RQNWPEDKRR YFIKMGSSVE NDNPGKEVNK
LSEHERSISP LLFEESPSDV QPPGDPFQVN FEEQNNPQIL QNSVVFGTSA QEVVKEIRFR
IEQKTTLTAS AGIAPNTMLA KVCSDKNKPN GQYQILPNRQ AVMDFIKDLP IRKVSGIGKV
TEKMLKALGI ITCTELYQQR ALLSLLFSET SWHYFLHISL GLGSTHLTRD GERKSMSVER
TFSEINKAEE QYSLCQELCS ELAQDLQKER LKGRTVTIKL KNVNFEVKTR ASTVSSVVST
AEEIFAIAKE LLKTEIDADF PHPLRLRLMG VRISSFPNEE DRKHQQRSII GFLQAGNQAL
SATECTLEKT DKDKFVKPLE MSHKKSFFDK KRSERKWSHQ DTFKCEAVNK QSFQTSQPFQ
VLKKKMNENL EISENSDDCQ ILTCPVCFRA QGCISLEALN KHVDECLDGP SISENFKMFS
CSHVSATKVN KKENVPASSL CEKQDYEAHP KIKEISSVDC IALVDTIDNS SKAESIDALS
NKHSKEECSS LPSKSFNIEH CHQNSSSTVS LENEDVGSFR QEYRQPYLCE VKTGQALVCP
VCNVEQKTSD LTLFNVHVDV CLNKSFIQEL RKDKFNPVNQ PKESSRSTGS SSGVQKAVTR
TKRPGLMTKY STSKKIKPNN PKHTLDIFFK