ID POLK_HUMAN Reviewed; 870 AA. AC Q9UBT6; Q86VJ8; Q8IZY0; Q8IZY1; Q8NB30; Q96L01; Q96Q86; Q96Q87; AC Q9UHC5; DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 23-OCT-2007, entry version 50. DE DNA polymerase kappa (EC 2.7.7.7) (DINB protein) (DINP). GN Name=POLK; Synonyms=DINB1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; 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 PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). 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, AND MUTAGENESIS OF ASP-198 AND 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). CC -!- FUNCTION: DNA polymerase specifically involved in DNA repair. CC Plays an important role in translesion synthesis, where the normal CC high-fidelity DNA polymerases cannot proceed and DNA synthesis CC stalls. Depending on the context, it inserts the correct base, but CC causes frequent base transitions, transversions and frameshifts. CC Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base CC with 5'-deoxyribose phosphate at abasic sites, but does not have CC lyase activity. CC -!- CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) = CC diphosphate + DNA(n+1). CC -!- COFACTOR: Divalent metal cations. Prefers magnesium, but can also CC use manganese. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 6.5-7.5; CC Temperature dependence: CC Optimum temperature is 37 degrees Celsius; CC -!- SUBUNIT: Binds REV1L (By similarity). Binds PCNA. CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Detected throughout the CC nucleus and at replication foci. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q9UBT6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UBT6-2; Sequence=VSP_012801, VSP_012802; CC Note=No experimental confirmation available; CC Name=3; CC IsoId=Q9UBT6-3; Sequence=VSP_012803; CC Name=4; CC IsoId=Q9UBT6-4; Sequence=VSP_012804, VSP_012805, VSP_012806; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Detected at low levels in testis, spleen, CC prostate and ovary. Detected at very low levels in kidney, colon, CC brain, heart, liver, lung, placenta, pancreas and peripheral blood CC leukocytes. CC -!- DOMAIN: The catalytic core consists of fingers, palm and thumb CC subdomains, but the fingers and thumb subdomains are much smaller CC than in high-fidelity polymerases; residues from five sequence CC motifs of the Y-family cluster around an active site cleft that CC can accommodate DNA and nucleotide substrates with relaxed CC geometric constraints, with consequently higher rates of CC misincorporation and low processivity. CC -!- SIMILARITY: Belongs to the DNA polymerase type-Y family. CC -!- SIMILARITY: Contains 2 Rad18-type zinc fingers. CC -!- SIMILARITY: Contains 1 umuC domain. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB027564; BAA86943.1; -; mRNA. DR EMBL; AF163570; AAF02540.1; -; mRNA. DR EMBL; AF194973; AAF23270.1; -; mRNA. DR EMBL; AF315602; AAN15780.1; -; mRNA. DR EMBL; AF318313; AAN15781.1; -; mRNA. DR EMBL; AY273797; AAP12648.1; -; Genomic_DNA. DR EMBL; AK091659; BAC03714.1; -; mRNA. DR EMBL; BC014955; AAH14955.1; -; mRNA. DR EMBL; BC050718; AAH50718.1; -; mRNA. DR EMBL; AB036934; BAB58975.1; -; Genomic_DNA. DR EMBL; AB036935; BAB58976.1; -; Genomic_DNA. DR RefSeq; NP_057302.1; -. DR UniGene; Hs.135756; -. DR PDB; 1T94; X-ray; A/B=68-526. DR SMR; Q9UBT6; 21-517. DR Ensembl; ENSG00000122008; Homo sapiens. DR GeneID; 51426; -. DR KEGG; hsa:51426; -. DR HGNC; HGNC:9183; POLK. DR MIM; 605650; gene. DR PharmGKB; PA33503; -. DR ArrayExpress; Q9UBT6; -. DR GO; GO:0006280; P:mutagenesis; TAS:ProtInc. DR InterPro; IPR001126; UMUC_like. DR InterPro; IPR006642; Znf_Rad18_put. DR Pfam; PF00817; IMS; 1. DR SMART; SM00734; ZnF_Rad18; 2. DR PROSITE; PS50173; UMUC; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; DNA damage; DNA repair; KW DNA replication; DNA synthesis; DNA-binding; KW DNA-directed DNA polymerase; Magnesium; Metal-binding; KW Mutator protein; Nucleotidyltransferase; Nucleus; Polymorphism; KW Repeat; Schiff base; Transferase; Zinc; Zinc-finger. FT CHAIN 1 870 DNA polymerase kappa. FT /FTId=PRO_0000173990. FT DOMAIN 103 358 UmuC. FT ZN_FING 621 647 Rad18-type 1. FT ZN_FING 776 802 Rad18-type 2. FT METAL 107 107 Magnesium (By similarity). FT METAL 198 198 Magnesium (By similarity). FT METAL 199 199 Magnesium (By similarity). FT VAR_SEQ 1 90 Missing (in isoform 4). FT /FTId=VSP_012804. FT VAR_SEQ 312 509 Missing (in isoform 3). FT /FTId=VSP_012803. FT VAR_SEQ 453 472 GRTVTIKLKNVNFEVKTRAS -> VLYFDMVSLVFKFFNSK FT MLP (in isoform 2). FT /FTId=VSP_012801. FT VAR_SEQ 453 462 GRTVTIKLKN -> KKYLPLLRNC (in isoform 4). FT /FTId=VSP_012805. FT VAR_SEQ 463 870 Missing (in isoform 4). FT /FTId=VSP_012806. FT VAR_SEQ 473 870 Missing (in isoform 2). FT /FTId=VSP_012802. FT VARIANT 595 595 T -> I (in dbSNP:rs5744713). FT /FTId=VAR_021246. FT VARIANT 612 612 I -> V (in dbSNP:rs3822587). FT /FTId=VAR_021247. FT VARIANT 832 832 S -> N (in dbSNP:rs5744716). FT /FTId=VAR_021248. FT MUTAGEN 198 198 D->A: Loss of DNA polymerase activity; FT when associated with A-199. FT MUTAGEN 199 199 E->A: Loss of DNA polymerase activity; FT when associated with D-198. FT CONFLICT 21 21 L -> F (in Ref. 8; BAB58975). FT CONFLICT 39 39 I -> T (in Ref. 8; BAB58975). FT CONFLICT 219 219 R -> L (in Ref. 8; BAB58976). FT CONFLICT 342 342 V -> G (in Ref. 6). FT CONFLICT 557 557 K -> N (in Ref. 3). FT CONFLICT 847 847 M -> V (in Ref. 3). FT HELIX 78 94 FT STRAND 103 108 FT HELIX 111 119 FT HELIX 121 123 FT STRAND 128 131 FT STRAND 136 139 FT HELIX 141 145 FT HELIX 154 160 FT STRAND 165 167 FT HELIX 171 188 FT STRAND 196 203 FT HELIX 205 211 FT HELIX 216 218 FT STRAND 219 222 FT HELIX 236 241 FT TURN 243 248 FT HELIX 249 251 FT STRAND 283 285 FT HELIX 290 305 FT STRAND 309 316 FT HELIX 317 326 FT TURN 327 330 FT STRAND 332 334 FT HELIX 339 346 FT HELIX 351 353 FT HELIX 359 367 FT HELIX 373 378 FT HELIX 380 386 FT HELIX 389 399 FT STRAND 416 425 FT HELIX 428 439 FT STRAND 456 462 FT STRAND 467 470 FT HELIX 484 496 FT STRAND 497 499 FT STRAND 506 513 SQ SEQUENCE 870 AA; 98809 MW; 40CB259A65F6A796 CRC64; 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 //