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 02-SEP-2026, entry version 217. 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). RN [29] RP VARIANT ASN-293, CHARACTERIZATION OF VARIANT ASN-293, AND INTERACTION WITH RP POLD1 AND POLD3. RX PubMed=31449058; DOI=10.1172/jci128903; RA Conde C.D., Petronczki O.Y., Baris S., Willmann K.L., Girardi E., RA Salzer E., Weitzer S., Ardy R.C., Krolo A., Ijspeert H., Kiykim A., RA Karakoc-Aydiner E., Foerster-Waldl E., Kager L., Pickl W.F., RA Superti-Furga G., Martinez J., Loizou J.I., Ozen A., van der Burg M., RA Boztug K.; RT "Polymerase delta deficiency causes syndromic immunodeficiency with RT replicative stress."; RL J. Clin. Invest. 129:4194-4206(2019). CC -!- FUNCTION: Accessory component of both the DNA polymerase delta complex CC and the DNA polymerase zeta complex (PubMed:17317665, PubMed:22801543, 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:17317665, PubMed:22801543, PubMed:24449906, CC PubMed:31449058). Component of the tetrameric DNA polymerase delta CC complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, CC POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' CC to 5' proofreading exonuclease activities (PubMed:17317665, CC PubMed:22801543). Within Pol-delta4, directly interacts with POLD1, CC POLD3 and POLD4 (PubMed:11328591, PubMed:16510448). Following stress CC caused by DNA damaging agents or by replication stress, POLD4 is CC degraded and Pol-delta4 is converted into a trimeric form of the CC complex (Pol-delta3), which consists of POLD1, POLD2 and POLD3. Pol- CC delta3 is the major form occurring at S phase replication sites, as CC well as DNA damage sites (PubMed:17317665, PubMed:22801543). Also CC observed as a dimeric complex with POLD2 (Pol-delta2 complex). Pol- CC delta2 is relatively insensitive to the PCNA stimulation (2-5-fold) CC compared to Pol-delta4 that is stimulated by over 50-fold CC (PubMed:12403614). Contrary to the other components of Pol-delta4, does CC not directly interact with PCNA (PubMed:12403614, PubMed:16510448). As CC POLD1 and POLD4, directly interacts with WRNIP1; this interaction CC stimulates DNA polymerase delta-mediated DNA synthesis, independently CC of the presence of PCNA. This stimulation may be due predominantly to CC an increase of initiation frequency and also to increased processivity CC (PubMed:15670210). Directly interacts with POLDIP2 and POLDIP3 CC (PubMed:12522211). Directly interacts with KCTD13/PDIP1; in the CC presence of PCNA, this interaction may stimulate DNA polymerase CC activity (PubMed:11593007). Component of the tetrameric Pol-zeta CC complex (Pol-zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3, CC with REV3L bearing DNA polymerase catalytic activity (PubMed:24449906). CC Interacts with KCTD10 (By similarity). {ECO:0000250|UniProtKB:Q6AXY4, CC ECO:0000269|PubMed:11328591, ECO:0000269|PubMed:11593007, CC ECO:0000269|PubMed:12403614, ECO:0000269|PubMed:12522211, CC ECO:0000269|PubMed:15670210, ECO:0000269|PubMed:16510448, CC ECO:0000269|PubMed:17317665, ECO:0000269|PubMed:22801543, CC ECO:0000269|PubMed:24449906, ECO:0000269|PubMed:31449058}. CC -!- INTERACTION: CC P49005; P12004: PCNA; NbExp=3; IntAct=EBI-372354, EBI-358311; CC P49005; P28340: POLD1; NbExp=16; IntAct=EBI-372354, EBI-716569; CC P49005; Q15054: POLD3; NbExp=11; IntAct=EBI-372354, EBI-864956; CC P49005; Q9HCU8: POLD4; NbExp=7; 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 --------------------------------------------------------------------------- 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; 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 PIR; I38950; I38950. DR RefSeq; NP_001120690.1; NM_001127218.3. DR RefSeq; NP_001243808.1; NM_001256879.2. DR RefSeq; NP_006221.3; NM_006230.4. DR RefSeq; XP_024302570.1; XM_024446802.2. DR RefSeq; XP_047276455.1; XM_047420499.1. DR RefSeq; XP_047276456.1; XM_047420500.1. DR RefSeq; XP_047276457.1; XM_047420501.1. DR RefSeq; XP_054214436.1; XM_054358461.1. DR RefSeq; XP_054214437.1; XM_054358462.1. DR RefSeq; XP_054214438.1; XM_054358463.1. DR RefSeq; XP_054214439.1; XM_054358464.1. 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 PDB; 9EKB; EM; 3.65 A; B=1-469. DR AlphaFoldDB; P49005; -. DR EMDB; EMD-10080; -. DR EMDB; EMD-10081; -. DR EMDB; EMD-10082; -. DR EMDB; EMD-10539; -. DR EMDB; EMD-10540; -. DR EMDB; EMD-48117; -. DR SMR; P49005; -. DR BioGRID; 111421; 81. DR ComplexPortal; CPX-2097; DNA polymerase delta complex. DR ComplexPortal; CPX-994; DNA polymerase zeta complex. DR CORUM; P49005; -. DR FunCoup; P49005; 1499. DR IntAct; P49005; 39. DR MINT; P49005; -. DR NDEx; IQUERY-CP-POLD2; 12 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000480186; -. DR BindingDB; P49005; -. DR ChEMBL; CHEMBL2763; -. DR GlyCosmos; P49005; 1 site, 1 glycan. DR GlyGen; P49005; 4 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; P49005; -. DR PhosphoSitePlus; P49005; -. DR BioMuta; POLD2; -. DR DMDM; 1352307; -. DR jPOST; P49005; -. DR MassIVE; P49005; -. DR PaxDb; 9606-ENSP00000480186; -. DR PeptideAtlas; P49005; -. DR ProteomicsDB; 55954; -. DR Pumba; P49005; -. DR Antibodypedia; 13259; 204 antibodies from 29 providers. DR DNASU; 5425; -. DR Ensembl; ENST00000406581.6; ENSP00000386105.2; ENSG00000106628.14. DR Ensembl; ENST00000418438.2; ENSP00000406702.2; ENSG00000106628.14. DR Ensembl; ENST00000452185.5; ENSP00000395231.1; ENSG00000106628.14. DR Ensembl; ENST00000610533.6; ENSP00000480186.2; ENSG00000106628.14. DR Ensembl; ENST00000698945.1; ENSP00000514051.1; ENSG00000106628.14. DR Ensembl; ENST00000698946.1; ENSP00000514052.1; ENSG00000106628.14. DR Ensembl; ENST00000698947.1; ENSP00000514053.1; ENSG00000106628.14. DR Ensembl; ENST00000881299.1; ENSP00000551358.1; ENSG00000106628.14. DR Ensembl; ENST00000881300.1; ENSP00000551359.1; ENSG00000106628.14. DR Ensembl; ENST00000881304.1; ENSP00000551363.1; ENSG00000106628.14. DR Ensembl; ENST00000881305.1; ENSP00000551364.1; ENSG00000106628.14. DR Ensembl; ENST00000881316.1; ENSP00000551375.1; ENSG00000106628.14. DR Ensembl; ENST00000881321.1; ENSP00000551380.1; ENSG00000106628.14. DR Ensembl; ENST00000881322.1; ENSP00000551381.1; ENSG00000106628.14. DR Ensembl; ENST00000881323.1; ENSP00000551382.1; ENSG00000106628.14. DR Ensembl; ENST00000931684.1; ENSP00000601743.1; ENSG00000106628.14. DR Ensembl; ENST00000931686.1; ENSP00000601745.1; ENSG00000106628.14. DR Ensembl; ENST00000931687.1; ENSP00000601746.1; ENSG00000106628.14. DR Ensembl; ENST00000964228.1; ENSP00000634287.1; ENSG00000106628.14. DR Ensembl; ENST00000964229.1; ENSP00000634288.1; ENSG00000106628.14. DR Ensembl; ENST00000964230.1; ENSP00000634289.1; ENSG00000106628.14. DR Ensembl; ENST00000964231.1; ENSP00000634290.1; ENSG00000106628.14. DR Ensembl; ENST00000964238.1; ENSP00000634297.1; ENSG00000106628.14. 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 AGR; HGNC:9176; -. DR ClinPGx; PA33497; -. DR CTD; 5425; -. DR DisGeNET; 5425; -. DR GeneCards; POLD2; -. DR HGNC; HGNC:9176; POLD2. DR HPA; ENSG00000106628; Low tissue specificity. DR MalaCards; POLD2; -. DR MIM; 600815; gene. DR OpenTargets; ENSG00000106628; -. DR Orphanet; 718047; Combined immunodeficiency due to polymerase delta deficiency. DR VEuPathDB; HostDB:ENSG00000106628; -. DR eggNOG; KOG2732; Eukaryota. DR GeneTree; ENSGT00390000006780; -. DR HOGENOM; CLU_021763_0_0_1; -. DR InParanoid; P49005; -. DR OMA; HCILIGT; -. DR OrthoDB; 3763at2759; -. DR PAN-GO; P49005; 2 GO annotations based on evolutionary models. DR PhylomeDB; P49005; -. 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 Agora; ENSG00000106628; -. DR BioGRID-ORCS; 5425; 775 hits in 1162 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 205 other cell types or tissues. DR ExpressionAtlas; P49005; baseline and differential. DR GO; GO:0043625; C:delta DNA polymerase complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; EXP:UniProtKB. 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 FunFam; 3.60.21.50:FF:000001; DNA polymerase delta 2, accessory subunit; 1. DR FunFam; 3.60.21.50:FF:000008; DNA polymerase delta 2, accessory subunit; 1. DR FunFam; 2.40.50.430:FF:000001; DNA polymerase delta subunit 2; 1. DR Gene3D; 2.40.50.430; -; 1. DR Gene3D; 3.60.21.50; -; 1. 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; DNA POLYMERASE DELTA SUBUNIT 2; 1. DR PANTHER; PTHR10416:SF0; DNA POLYMERASE DELTA SUBUNIT 2; 1. DR Pfam; PF18018; DNA_pol_D_N; 1. DR Pfam; PF04042; DNA_pol_E_B; 1. DR PDBsum; 3E0J; -. DR PDBsum; 6S1M; -. DR PDBsum; 6S1N; -. DR PDBsum; 6S1O; -. DR PDBsum; 6TNY; -. DR PDBsum; 6TNZ; -. DR PDBsum; 9EKB; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; DNA damage; DNA excision; DNA repair; KW DNA replication; Nucleus; Phosphoprotein; Proteomics identification; KW 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 293 FT /note="D -> N (found in a patient with a syndromic combined FT immunodeficiency disorder; uncertain significance; affects FT protein stability; strongly reduced interaction with POLD1 FT and POLD3; in peripheral blood mononuclear cells, after FT anti-CD3 and anti-CD28 stimulation, drastically reduced FT protein expression levels, despite transcript levels FT similar to that of wild-type controls; patient's cells also FT show strongly decreased POLD1 and POLD3 protein levels; no FT effect on DNA polymerase activity, when tested in FT transfected HEK293 cells)" FT /evidence="ECO:0000269|PubMed:31449058" FT /id="VAR_089632" 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 HELIX 26..28 FT /evidence="ECO:0007829|PDB:6TNY" 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..178 FT /evidence="ECO:0007829|PDB:3E0J" FT HELIX 181..183 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 185..189 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 308..312 FT /evidence="ECO:0007829|PDB:6TNY" 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..381 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 //