DPOD2_HUMAN
ID DPOD2_HUMAN Reviewed; 469 AA.
AC P49005; A4D2J4; B2R5S4;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=DNA polymerase delta subunit 2;
DE AltName: Full=DNA polymerase delta subunit p50;
GN Name=POLD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8530069; DOI=10.1006/geno.1995.1229;
RA Zhang J., Tan C.-K., McMullen B., Downey K.M., So A.G.;
RT "Cloning of the cDNAs for the small subunits of bovine and human DNA
RT polymerase delta and chromosomal location of the human gene (POLD2).";
RL Genomics 29:179-186(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10978529; DOI=10.1016/s0167-4781(00)00153-6;
RA Perez A., Leon A., Lee M.Y.W.T.;
RT "Characterization of the 5'-flanking region of the gene encoding the 50 kDa
RT subunit of human DNA polymerase delta.";
RL Biochim. Biophys. Acta 1493:231-236(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-303.
RG NIEHS SNPs program;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH POLD1 AND POLD3.
RX PubMed=11328591; DOI=10.1093/oxfordjournals.jbchem.a002909;
RA Shikata K., Ohta S., Yamada K., Obuse C., Yoshikawa H., Tsurimoto T.;
RT "The human homologue of fission Yeast cdc27, p66, is a component of active
RT human DNA polymerase delta.";
RL J. Biochem. 129:699-708(2001).
RN [9]
RP INTERACTION WITH KCTD13.
RX PubMed=11593007; DOI=10.1073/pnas.221452098;
RA He H., Tan C.-K., Downey K.M., So A.G.;
RT "A tumor necrosis factor alpha- and interleukin 6-inducible protein that
RT interacts with the small subunit of DNA polymerase delta and proliferating
RT cell nuclear antigen.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:11979-11984(2001).
RN [10]
RP FUNCTION, CHARACTERIZATION OF POL-DELTA2 AND POL-DELTA4 COMPLEXES, AND LACK
RP OF INTERACTION WITH PCNA.
RX PubMed=12403614; DOI=10.1021/bi0262707;
RA Xie B., Mazloum N., Liu L., Rahmeh A., Li H., Lee M.Y.;
RT "Reconstitution and characterization of the human DNA polymerase delta
RT four-subunit holoenzyme.";
RL Biochemistry 41:13133-13142(2002).
RN [11]
RP INTERACTION WITH POLD1; POLDIP2 AND POLDIP3.
RX PubMed=12522211; DOI=10.1074/jbc.m208694200;
RA Liu L., Rodriguez-Belmonte E.M., Mazloum N., Xie B., Lee M.Y.W.T.;
RT "Identification of a novel protein, PDIP38, that interacts with the p50
RT subunit of DNA polymerase delta and proliferating cell nuclear antigen.";
RL J. Biol. Chem. 278:10041-10047(2003).
RN [12]
RP INTERACTION WITH WRNIP1.
RX PubMed=15670210; DOI=10.1111/j.1365-2443.2004.00812.x;
RA Tsurimoto T., Shinozaki A., Yano M., Seki M., Enomoto T.;
RT "Human Werner helicase interacting protein 1 (WRNIP1) functions as a novel
RT modulator for DNA polymerase delta.";
RL Genes Cells 10:13-22(2005).
RN [13]
RP FUNCTION, INTERACTION WITH POLD1; POLD3 AND POLD4, AND LACK OF INTERACTION
RP WITH PCNA.
RX PubMed=16510448; DOI=10.1074/jbc.m600322200;
RA Li H., Xie B., Zhou Y., Rahmeh A., Trusa S., Zhang S., Gao Y., Lee E.Y.,
RA Lee M.Y.;
RT "Functional roles of p12, the fourth subunit of human DNA polymerase
RT delta.";
RL J. Biol. Chem. 281:14748-14755(2006).
RN [14]
RP IDENTIFICATION IN POL-DELTA COMPLEX.
RX PubMed=17317665; DOI=10.1074/jbc.m610356200;
RA Zhang S., Zhou Y., Trusa S., Meng X., Lee E.Y., Lee M.Y.;
RT "A novel DNA damage response: rapid degradation of the p12 subunit of dna
RT polymerase delta.";
RL J. Biol. Chem. 282:15330-15340(2007).
RN [15]
RP FUNCTION, AND CHARACTERIZATION OF POL-DELTA3 AND POL-DELTA4.
RX PubMed=19074196; DOI=10.1093/nar/gkn1000;
RA Meng X., Zhou Y., Zhang S., Lee E.Y., Frick D.N., Lee M.Y.;
RT "DNA damage alters DNA polymerase delta to a form that exhibits increased
RT discrimination against modified template bases and mismatched primers.";
RL Nucleic Acids Res. 37:647-657(2009).
RN [16]
RP FUNCTION, AND IDENTIFICATION IN POL-DELTA COMPLEX.
RX PubMed=20334433; DOI=10.1021/bi100042b;
RA Meng X., Zhou Y., Lee E.Y., Lee M.Y., Frick D.N.;
RT "The p12 subunit of human polymerase delta modulates the rate and fidelity
RT of DNA synthesis.";
RL Biochemistry 49:3545-3554(2010).
RN [17]
RP FUNCTION IN NUCLEOTIDE EXCISION REPAIR.
RX PubMed=20227374; DOI=10.1016/j.molcel.2010.02.009;
RA Ogi T., Limsirichaikul S., Overmeer R.M., Volker M., Takenaka K.,
RA Cloney R., Nakazawa Y., Niimi A., Miki Y., Jaspers N.G., Mullenders L.H.,
RA Yamashita S., Fousteri M.I., Lehmann A.R.;
RT "Three DNA polymerases, recruited by different mechanisms, carry out NER
RT repair synthesis in human cells.";
RL Mol. Cell 37:714-727(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP SUBCELLULAR LOCATION, IDENTIFICATION IN POL-DELTA COMPLEX, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=22801543; DOI=10.4161/cc.21280;
RA Chea J., Zhang S., Zhao H., Zhang Z., Lee E.Y., Darzynkiewicz Z., Lee M.Y.;
RT "Spatiotemporal recruitment of human DNA polymerase delta to sites of UV
RT damage.";
RL Cell Cycle 11:2885-2895(2012).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [22]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [23]
RP FUNCTION IN OKAZAKI FRAGMENT PROCESSING.
RX PubMed=24035200; DOI=10.1016/j.dnarep.2013.08.008;
RA Lin S.H., Wang X., Zhang S., Zhang Z., Lee E.Y., Lee M.Y.;
RT "Dynamics of enzymatic interactions during short flap human Okazaki
RT fragment processing by two forms of human DNA polymerase delta.";
RL DNA Repair 12:922-935(2013).
RN [24]
RP POL-DELTA3 COMPLEX EXPRESSION DURING CELL CYCLE.
RX PubMed=23913683; DOI=10.1074/jbc.m113.490466;
RA Zhang S., Zhao H., Darzynkiewicz Z., Zhou P., Zhang Z., Lee E.Y., Lee M.Y.;
RT "A novel function of CRL4(Cdt2): regulation of the subunit structure of DNA
RT polymerase delta in response to DNA damage and during the S phase.";
RL J. Biol. Chem. 288:29550-29561(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15 AND SER-257, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP FUNCTION, IDENTIFICATION IN POL-DELTA COMPLEX, AND IDENTIFICATION IN
RP POL-ZETA COMPLEX.
RX PubMed=24449906; DOI=10.1073/pnas.1324001111;
RA Lee Y.S., Gregory M.T., Yang W.;
RT "Human Pol zeta purified with accessory subunits is active in translesion
RT DNA synthesis and complements Pol eta in cisplatin bypass.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:2954-2959(2014).
RN [27]
RP FUNCTION IN BIR.
RX PubMed=24310611; DOI=10.1126/science.1243211;
RA Costantino L., Sotiriou S.K., Rantala J.K., Magin S., Mladenov E.,
RA Helleday T., Haber J.E., Iliakis G., Kallioniemi O.P., Halazonetis T.D.;
RT "Break-induced replication repair of damaged forks induces genomic
RT duplications in human cells.";
RL Science 343:88-91(2014).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH POLD3, AND
RP MUTAGENESIS OF LEU-217; GLY-224 AND GLU-231.
RX PubMed=18818516; DOI=10.4161/cc.7.19.6720;
RA Baranovskiy A.G., Babayeva N.D., Liston V.G., Rogozin I.B., Koonin E.V.,
RA Pavlov Y.I., Vassylyev D.G., Tahirov T.H.;
RT "X-ray structure of the complex of regulatory subunits of human DNA
RT polymerase delta.";
RL Cell Cycle 7:3026-3036(2008).
CC -!- FUNCTION: Accessory component of both the DNA polymerase delta complex
CC and the DNA polymerase zeta complex (PubMed:22801543, PubMed:17317665,
CC PubMed:24449906). As a component of the trimeric and tetrameric DNA
CC polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively),
CC plays a role in high fidelity genome replication, including in lagging
CC strand synthesis, and repair (PubMed:12403614, PubMed:16510448,
CC PubMed:19074196, PubMed:20334433, PubMed:24035200). Pol-delta3 and Pol-
CC delta4 are characterized by the absence or the presence of POLD4. They
CC exhibit differences in catalytic activity. Most notably, Pol-delta3
CC shows higher proofreading activity than Pol-delta4 (PubMed:19074196,
CC PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process
CC Okazaki fragments in vitro, Pol-delta3 may also be better suited to
CC fulfill this task, exhibiting near-absence of strand displacement
CC activity compared to Pol-delta4 and stalling on encounter with the 5'-
CC blocking oligonucleotides. Pol-delta3 idling process may avoid the
CC formation of a gap, while maintaining a nick that can be readily
CC ligated (PubMed:24035200). Along with DNA polymerase kappa, DNA
CC polymerase delta carries out approximately half of nucleotide excision
CC repair (NER) synthesis following UV irradiation (PubMed:20227374).
CC Under conditions of DNA replication stress, required for the repair of
CC broken replication forks through break-induced replication (BIR)
CC (PubMed:24310611). Involved in the translesion synthesis (TLS) of
CC templates carrying O6-methylguanine or abasic sites performed by Pol-
CC delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH).
CC Facilitates abasic site bypass by DNA polymerase delta by promoting
CC extension from the nucleotide inserted opposite the lesion. Also
CC involved in TLS as a component of the DNA polymerase zeta complex
CC (PubMed:24449906). Along with POLD3, dramatically increases the
CC efficiency and processivity of DNA synthesis of the DNA polymerase zeta
CC complex compared to the minimal zeta complex, consisting of only REV3L
CC and REV7 (PubMed:24449906). {ECO:0000269|PubMed:12403614,
CC ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196,
CC ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433,
CC ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611,
CC ECO:0000269|PubMed:24449906}.
CC -!- SUBUNIT: Component of both the DNA polymerase delta and DNA polymerase
CC zeta complexes (PubMed:22801543, PubMed:17317665, PubMed:24449906).
CC Component of the tetrameric DNA polymerase delta complex (Pol-delta4),
CC which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12,
CC with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease
CC activities (PubMed:22801543, PubMed:17317665). Within Pol-delta4,
CC directly interacts with POLD1, POLD3 and POLD4 (PubMed:11328591,
CC PubMed:16510448). Following stress caused by DNA damaging agents or by
CC replication stress, POLD4 is degraded and Pol-delta4 is converted into
CC a trimeric form of the complex (Pol-delta3), which consists of POLD1,
CC POLD2 and POLD3. Pol-delta3 is the major form occurring at S phase
CC replication sites, as well as DNA damage sites (PubMed:22801543,
CC PubMed:17317665). Also observed as a dimeric complex with POLD2 (Pol-
CC delta2 complex). Pol-delta2 is relatively insensitive to the PCNA
CC stimulation (2-5-fold) compared to Pol-delta4 that is stimulated by
CC over 50-fold (PubMed:12403614). Contrary to the other components of
CC Pol-delta4, does not directly interact with PCNA (PubMed:12403614,
CC PubMed:16510448). As POLD1 and POLD4, directly interacts with WRNIP1;
CC this interaction stimulates DNA polymerase delta-mediated DNA
CC synthesis, independently of the presence of PCNA. This stimulation may
CC be due predominantly to an increase of initiation frequency and also to
CC increased processivity (PubMed:15670210). Directly interacts with
CC POLDIP2 and POLDIP3 (PubMed:12522211). Directly interacts with
CC KCTD13/PDIP1; in the presence of PCNA, this interaction may stimulate
CC DNA polymerase activity (PubMed:11593007). Component of the tetrameric
CC Pol-zeta complex (Pol-zeta4), which consists of REV3L, MAD2L2, POLD2
CC and POLD3, with REV3L bearing DNA polymerase catalytic activity
CC (PubMed:24449906). Interacts with KCTD10 (By similarity).
CC {ECO:0000250|UniProtKB:Q6AXY4, ECO:0000269|PubMed:11328591,
CC ECO:0000269|PubMed:11593007, ECO:0000269|PubMed:12403614,
CC ECO:0000269|PubMed:12522211, ECO:0000269|PubMed:15670210,
CC ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:17317665,
CC ECO:0000269|PubMed:22801543, ECO:0000269|PubMed:24449906}.
CC -!- INTERACTION:
CC P49005; P12004: PCNA; NbExp=3; IntAct=EBI-372354, EBI-358311;
CC P49005; P28340: POLD1; NbExp=14; IntAct=EBI-372354, EBI-716569;
CC P49005; Q15054: POLD3; NbExp=8; IntAct=EBI-372354, EBI-864956;
CC P49005; Q9HCU8: POLD4; NbExp=5; IntAct=EBI-372354, EBI-864968;
CC P49005; Q96S55: WRNIP1; NbExp=2; IntAct=EBI-372354, EBI-2513471;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22801543}.
CC Note=Recruited to DNA damage sites within 2 hours following UV
CC irradiation. {ECO:0000269|PubMed:22801543}.
CC -!- DEVELOPMENTAL STAGE: Expression is cell cycle-dependent, with highest
CC levels in G2/M phase and lowest in S. {ECO:0000269|PubMed:22801543}.
CC -!- SIMILARITY: Belongs to the DNA polymerase delta/II small subunit
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/pold2/";
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DR EMBL; U21090; AAC50216.1; -; mRNA.
DR EMBL; AF239710; AAG09763.1; -; Genomic_DNA.
DR EMBL; AY116646; AAM51148.1; -; Genomic_DNA.
DR EMBL; AK292347; BAF85036.1; -; mRNA.
DR EMBL; AK312294; BAG35221.1; -; mRNA.
DR EMBL; CH236960; EAL23767.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW61118.1; -; Genomic_DNA.
DR EMBL; BC000459; AAH00459.1; -; mRNA.
DR CCDS; CCDS5477.1; -.
DR CCDS; CCDS75586.1; -.
DR PIR; I38950; I38950.
DR RefSeq; NP_001120690.1; NM_001127218.2.
DR RefSeq; NP_001243808.1; NM_001256879.1.
DR RefSeq; NP_006221.2; NM_006230.3.
DR PDB; 3E0J; X-ray; 3.00 A; A/C/E/G=1-469.
DR PDB; 6S1M; EM; 4.27 A; B=1-469.
DR PDB; 6S1N; EM; 4.86 A; B=1-469.
DR PDB; 6S1O; EM; 8.10 A; B=1-469.
DR PDB; 6TNY; EM; 3.08 A; B=1-469.
DR PDB; 6TNZ; EM; 4.05 A; B=1-469.
DR PDBsum; 3E0J; -.
DR PDBsum; 6S1M; -.
DR PDBsum; 6S1N; -.
DR PDBsum; 6S1O; -.
DR PDBsum; 6TNY; -.
DR PDBsum; 6TNZ; -.
DR AlphaFoldDB; P49005; -.
DR SMR; P49005; -.
DR BioGRID; 111421; 57.
DR ComplexPortal; CPX-2097; DNA polymerase delta complex.
DR ComplexPortal; CPX-994; DNA polymerase zeta complex.
DR CORUM; P49005; -.
DR IntAct; P49005; 28.
DR MINT; P49005; -.
DR STRING; 9606.ENSP00000480186; -.
DR ChEMBL; CHEMBL2363042; -.
DR GlyGen; P49005; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P49005; -.
DR PhosphoSitePlus; P49005; -.
DR BioMuta; POLD2; -.
DR DMDM; 1352307; -.
DR EPD; P49005; -.
DR jPOST; P49005; -.
DR MassIVE; P49005; -.
DR MaxQB; P49005; -.
DR PaxDb; P49005; -.
DR PeptideAtlas; P49005; -.
DR PRIDE; P49005; -.
DR ProteomicsDB; 55954; -.
DR Antibodypedia; 13259; 216 antibodies from 28 providers.
DR DNASU; 5425; -.
DR Ensembl; ENST00000406581.6; ENSP00000386105.2; ENSG00000106628.12.
DR Ensembl; ENST00000452185.5; ENSP00000395231.1; ENSG00000106628.12.
DR Ensembl; ENST00000610533.6; ENSP00000480186.2; ENSG00000106628.12.
DR GeneID; 5425; -.
DR KEGG; hsa:5425; -.
DR MANE-Select; ENST00000610533.6; ENSP00000480186.2; NM_006230.4; NP_006221.3.
DR UCSC; uc010kxz.5; human.
DR CTD; 5425; -.
DR DisGeNET; 5425; -.
DR GeneCards; POLD2; -.
DR HGNC; HGNC:9176; POLD2.
DR HPA; ENSG00000106628; Low tissue specificity.
DR MIM; 600815; gene.
DR neXtProt; NX_P49005; -.
DR OpenTargets; ENSG00000106628; -.
DR PharmGKB; PA33497; -.
DR VEuPathDB; HostDB:ENSG00000106628; -.
DR eggNOG; KOG2732; Eukaryota.
DR GeneTree; ENSGT00390000006780; -.
DR HOGENOM; CLU_021763_0_0_1; -.
DR InParanoid; P49005; -.
DR OMA; DPANFML; -.
DR OrthoDB; 736068at2759; -.
DR PhylomeDB; P49005; -.
DR TreeFam; TF101073; -.
DR PathwayCommons; P49005; -.
DR Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-HSA-174411; Polymerase switching on the C-strand of the telomere.
DR Reactome; R-HSA-174414; Processive synthesis on the C-strand of the telomere.
DR Reactome; R-HSA-174417; Telomere C-strand (Lagging Strand) Synthesis.
DR Reactome; R-HSA-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-HSA-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis.
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5696397; Gap-filling DNA repair synthesis and ligation in GG-NER.
DR Reactome; R-HSA-5696400; Dual Incision in GG-NER.
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-HSA-69091; Polymerase switching.
DR Reactome; R-HSA-69166; Removal of the Flap Intermediate.
DR Reactome; R-HSA-69183; Processive synthesis on the lagging strand.
DR SignaLink; P49005; -.
DR SIGNOR; P49005; -.
DR BioGRID-ORCS; 5425; 739 hits in 1085 CRISPR screens.
DR ChiTaRS; POLD2; human.
DR EvolutionaryTrace; P49005; -.
DR GeneWiki; POLD2; -.
DR GenomeRNAi; 5425; -.
DR Pharos; P49005; Tbio.
DR PRO; PR:P49005; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P49005; protein.
DR Bgee; ENSG00000106628; Expressed in right uterine tube and 203 other tissues.
DR ExpressionAtlas; P49005; baseline and differential.
DR Genevisible; P49005; HS.
DR GO; GO:0043625; C:delta DNA polymerase complex; IDA:UniProtKB.
DR GO; GO:0042575; C:DNA polymerase complex; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0016035; C:zeta DNA polymerase complex; IDA:FlyBase.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0071897; P:DNA biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; IBA:GO_Central.
DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:ComplexPortal.
DR GO; GO:0042276; P:error-prone translesion synthesis; IDA:ComplexPortal.
DR CDD; cd07387; MPP_PolD2_C; 1.
DR DisProt; DP01807; -.
DR IDEAL; IID00051; -.
DR InterPro; IPR007185; DNA_pol_a/d/e_bsu.
DR InterPro; IPR040663; DNA_pol_D_N.
DR InterPro; IPR024826; DNA_pol_delta/II_ssu.
DR InterPro; IPR041863; PolD2_C.
DR PANTHER; PTHR10416; PTHR10416; 1.
DR Pfam; PF18018; DNA_pol_D_N; 1.
DR Pfam; PF04042; DNA_pol_E_B; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; DNA damage; DNA excision; DNA repair;
KW DNA replication; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..469
FT /note="DNA polymerase delta subunit 2"
FT /id="PRO_0000096166"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 303
FT /note="N -> S (in dbSNP:rs3087366)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_014885"
FT MUTAGEN 217
FT /note="L->W: Loss of POLD3-binding in a yeast two-hybrid
FT assay."
FT /evidence="ECO:0000269|PubMed:18818516"
FT MUTAGEN 224
FT /note="G->W: Loss of POLD3-binding in a yeast two-hybrid
FT assay."
FT /evidence="ECO:0000269|PubMed:18818516"
FT MUTAGEN 231
FT /note="E->W: Loss of POLD3-binding in a yeast two-hybrid
FT assay."
FT /evidence="ECO:0000269|PubMed:18818516"
FT CONFLICT 271
FT /note="A -> T (in Ref. 4; BAG35221)"
FT /evidence="ECO:0000305"
FT HELIX 2..7
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 13..16
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 55..72
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 91..100
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:3E0J"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 158..165
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 169..177
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 209..223
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 229..235
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 238..245
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 265..287
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 292..295
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 304..307
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 313..315
FT /evidence="ECO:0007829|PDB:6TNY"
FT HELIX 317..320
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 330..336
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 339..343
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 347..355
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 361..370
FT /evidence="ECO:0007829|PDB:3E0J"
FT TURN 378..380
FT /evidence="ECO:0007829|PDB:6TNY"
FT STRAND 400..409
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 411..416
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:6TNY"
FT STRAND 422..429
FT /evidence="ECO:0007829|PDB:3E0J"
FT HELIX 431..434
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 436..441
FT /evidence="ECO:0007829|PDB:3E0J"
FT TURN 442..445
FT /evidence="ECO:0007829|PDB:3E0J"
FT STRAND 449..454
FT /evidence="ECO:0007829|PDB:3E0J"
FT TURN 460..462
FT /evidence="ECO:0007829|PDB:3E0J"
SQ SEQUENCE 469 AA; 51289 MW; 389EF730999755AC CRC64;
MFSEQAAQRA HTLLSPPSAN NATFARVPVA TYTNSSQPFR LGERSFSRQY AHIYATRLIQ
MRPFLENRAQ QHWGSGVGVK KLCELQPEEK CCVVGTLFKA MPLQPSILRE VSEEHNLLPQ
PPRSKYIHPD DELVLEDELQ RIKLKGTIDV SKLVTGTVLA VFGSVRDDGK FLVEDYCFAD
LAPQKPAPPL DTDRFVLLVS GLGLGGGGGE SLLGTQLLVD VVTGQLGDEG EQCSAAHVSR
VILAGNLLSH STQSRDSINK AKYLTKKTQA ASVEAVKMLD EILLQLSASV PVDVMPGEFD
PTNYTLPQQP LHPCMFPLAT AYSTLQLVTN PYQATIDGVR FLGTSGQNVS DIFRYSSMED
HLEILEWTLR VRHISPTAPD TLGCYPFYKT DPFIFPECPH VYFCGNTPSF GSKIIRGPED
QTVLLVTVPD FSATQTACLV NLRSLACQPI SFSGFGAEDD DLGGLGLGP
