ID DPOD1_HUMAN Reviewed; 1107 AA. AC P28340; Q8NER3; Q96H98; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 19-JUL-2004, sequence version 2. DT 27-MAR-2024, entry version 224. DE RecName: Full=DNA polymerase delta catalytic subunit {ECO:0000305}; DE EC=2.7.7.7 {ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20334433}; DE AltName: Full=3'-5' exodeoxyribonuclease {ECO:0000305}; DE EC=3.1.11.- {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20334433}; DE AltName: Full=DNA polymerase subunit delta p125; GN Name=POLD1 {ECO:0000312|HGNC:HGNC:9175}; Synonyms=POLD; 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], AND VARIANT TRP-30. RC TISSUE=Hepatoma; RX PubMed=1722322; DOI=10.1073/pnas.88.24.11197; RA Chung D.W., Zhang J., Tan C.-K., Davie E.W., So A.G., Downey K.M.; RT "Primary structure of the catalytic subunit of human DNA polymerase delta RT and chromosomal location of the gene."; RL Proc. Natl. Acad. Sci. U.S.A. 88:11197-11201(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-119 AND ASN-173, AND INDUCTION BY RP SERUM. RC TISSUE=Cervix carcinoma; RX PubMed=1542570; DOI=10.1093/nar/20.4.735; RA Yang C.-L., Chang L.-S., Zhang P., Hao H., Zhu L., Toomey N.L., RA Lee M.Y.W.T.; RT "Molecular cloning of the cDNA for the catalytic subunit of human DNA RT polymerase delta."; RL Nucleic Acids Res. 20:735-745(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-19; TRP-30; HIS-119; RP ASN-173; HIS-177; HIS-849 AND GLN-1086. RG NIEHS SNPs program; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT HIS-119. RC TISSUE=Lymph; 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 [5] RP INTERACTION WITH POLD2 AND PCNA. 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 [6] RP INTERACTION WITH POLD3, AND SUBCELLULAR LOCATION. RX PubMed=11595739; DOI=10.1074/jbc.m106990200; RA Ducoux M., Urbach S., Baldacci G., Huebscher U., Koundrioukoff S., RA Christensen J., Hughes P.; RT "Mediation of proliferating cell nuclear antigen (PCNA)-dependent DNA RT replication through a conserved p21(Cip1)-like PCNA-binding motif present RT in the third subunit of human DNA polymerase delta."; RL J. Biol. Chem. 276:49258-49266(2001). RN [7] RP INTERACTION WITH PCNA AND POLD4, AND CHARACTERIZATION OF POL-DELTA2 AND RP POL-DELTA4 COMPLEXES. 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 [8] RP INTERACTION WITH POLD2 AND POLDIP2, AND STIMULATION BY PCNA. 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 [9] 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 [10] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH POLD2; POLD4 AND 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 [11] 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 [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-402, CHARACTERIZATION OF RP POL-DELTA3 AND POL-DELTA4, AND ACTIVITY REGULATION. 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 [14] RP FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF POL-DELTA3 AND RP POL-DELTA4, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ASP-402. 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 [15] RP FUNCTION IN NUCLEOTIDE EXCISION REPAIR, AND SUBCELLULAR LOCATION. 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 [16] 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 [17] RP SUBCELLULAR LOCATION, IDENTIFICATION IN POLD COMPLEX, AND DEVELOPMENTAL RP 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 [18] RP INTERACTION WITH CIAO1. RX PubMed=23891004; DOI=10.1016/j.cmet.2013.06.015; RA Stehling O., Mascarenhas J., Vashisht A.A., Sheftel A.D., Niggemeyer B., RA Roesser R., Pierik A.J., Wohlschlegel J.A., Lill R.; RT "Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and RT maturation of different subsets of cytosolic-nuclear iron-sulfur RT proteins."; RL Cell Metab. 18:187-198(2013). RN [19] RP ERRATUM OF PUBMED:23891004. RX PubMed=29320706; DOI=10.1016/j.cmet.2017.12.009; RA Stehling O., Mascarenhas J., Vashisht A.A., Sheftel A.D., Niggemeyer B., RA Roesser R., Pierik A.J., Wohlschlegel J.A., Lill R.; RT "Human CIA2A-FAM96A and CIA2B-FAM96B Integrate Iron Homeostasis and RT Maturation of Different Subsets of Cytosolic-Nuclear Iron-Sulfur RT Proteins."; RL Cell Metab. 27:263-263(2018). RN [20] 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 [21] 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 [22] RP FUNCTION, AND INTERACTION WITH PCNA. RX PubMed=24022480; DOI=10.1074/jbc.c113.505586; RA Terai K., Shibata E., Abbas T., Dutta A.; RT "Degradation of p12 subunit by CRL4Cdt2 E3 ligase inhibits fork progression RT after DNA damage."; RL J. Biol. Chem. 288:30509-30514(2013). RN [23] RP TISSUE SPECIFICITY, AND VARIANT MDPL SER-605 DEL. RX PubMed=23770608; DOI=10.1038/ng.2670; RA Weedon M.N., Ellard S., Prindle M.J., Caswell R., Allen H.L., Oram R., RA Godbole K., Yajnik C.S., Sbraccia P., Novelli G., Turnpenny P., McCann E., RA Goh K.J., Wang Y., Fulford J., McCulloch L.J., Savage D.B., O'Rahilly S., RA Kos K., Loeb L.A., Semple R.K., Hattersley A.T.; RT "An in-frame deletion at the polymerase active site of POLD1 causes a RT multisystem disorder with lipodystrophy."; RL Nat. Genet. 45:947-950(2013). RN [24] RP FUNCTION, AND INTERACTION WITH POLDIP2. RX PubMed=24191025; DOI=10.1073/pnas.1308760110; RA Maga G., Crespan E., Markkanen E., Imhof R., Furrer A., Villani G., RA Huebscher U., van Loon B.; RT "DNA polymerase delta-interacting protein 2 is a processivity factor for RT DNA polymerase lambda during 8-oxo-7,8-dihydroguanine bypass."; RL Proc. Natl. Acad. Sci. U.S.A. 110:18850-18855(2013). RN [25] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-19, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Colon carcinoma; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [26] RP INTERACTION WITH PCNA. RX PubMed=24939902; DOI=10.1093/nar/gku533; RA Cazzalini O., Sommatis S., Tillhon M., Dutto I., Bachi A., Rapp A., RA Nardo T., Scovassi A.I., Necchi D., Cardoso M.C., Stivala L.A., RA Prosperi E.; RT "CBP and p300 acetylate PCNA to link its degradation with nucleotide RT excision repair synthesis."; RL Nucleic Acids Res. 42:8433-8448(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 SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-574, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [29] RP VARIANTS ASP-145; HIS-461; ASN-478; LEU-787; HIS-808 AND THR-864, AND RP INVOLVEMENT IN CRCS10. RX PubMed=23263490; DOI=10.1038/ng.2503; RG CORGI Consortium; RG WGS500 Consortium; RA Palles C., Cazier J.B., Howarth K.M., Domingo E., Jones A.M., Broderick P., RA Kemp Z., Spain S.L., Guarino Almeida E., Salguero I., Sherborne A., RA Chubb D., Carvajal-Carmona L.G., Ma Y., Kaur K., Dobbins S., Barclay E., RA Gorman M., Martin L., Kovac M.B., Humphray S., Lucassen A., Holmes C.C., RA Bentley D., Donnelly P., Taylor J., Petridis C., Roylance R., Sawyer E.J., RA Kerr D.J., Clark S., Grimes J., Kearsey S.E., Thomas H.J., McVean G., RA Houlston R.S., Tomlinson I.; RT "Germline mutations affecting the proofreading domains of POLE and POLD1 RT predispose to colorectal adenomas and carcinomas."; RL Nat. Genet. 45:136-144(2013). RN [30] RP VARIANT CRCS10 PRO-474. RX PubMed=24501277; DOI=10.1093/hmg/ddu058; RA Valle L., Hernandez-Illan E., Bellido F., Aiza G., Castillejo A., RA Castillejo M.I., Navarro M., Segui N., Vargas G., Guarinos C., Juarez M., RA Sanjuan X., Iglesias S., Alenda C., Egoavil C., Segura A., Juan M.J., RA Rodriguez-Soler M., Brunet J., Gonzalez S., Jover R., Lazaro C., RA Capella G., Pineda M., Soto J.L., Blanco I.; RT "New insights into POLE and POLD1 germline mutations in familial colorectal RT cancer and polyposis."; RL Hum. Mol. Genet. 23:3506-3512(2014). CC -!- FUNCTION: As the catalytic component of the trimeric (Pol-delta3 CC complex) and tetrameric DNA polymerase delta complexes (Pol-delta4 CC complex), plays a crucial role in high fidelity genome replication, CC including in lagging strand synthesis, and repair. Exhibits both DNA CC polymerase and 3'- to 5'-exonuclease activities (PubMed:16510448, CC PubMed:19074196, PubMed:20334433, PubMed:24035200, PubMed:24022480). CC Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for CC full activity. Depending upon the absence (Pol-delta3) or the presence CC of POLD4 (Pol-delta4), displays differences in catalytic activity. Most CC notably, expresses higher proofreading activity in the context of Pol- CC delta3 compared with that of Pol-delta4 (PubMed:19074196, CC PubMed:20334433). Although both Pol-delta3 and Pol-delta4 process CC Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill CC this task, exhibiting near-absence of strand displacement activity CC compared to Pol-delta4 and stalling on encounter with the 5'-blocking CC oligonucleotides. Pol-delta3 idling process may avoid the formation of CC a gap, while maintaining a nick that can be readily ligated CC (PubMed:24035200). Along with DNA polymerase kappa, DNA polymerase CC delta carries out approximately half of nucleotide excision repair CC (NER) synthesis following UV irradiation (PubMed:20227374). Under CC conditions of DNA replication stress, in the presence of POLD3 and CC POLD4, may catalyze the repair of broken replication forks through CC break-induced replication (BIR) (PubMed:24310611). Involved in the CC translesion synthesis (TLS) of templates carrying O6-methylguanine, CC 8oxoG or abasic sites (PubMed:19074196, PubMed:24191025). CC {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, CC ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, CC ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, CC ECO:0000269|PubMed:24191025, ECO:0000269|PubMed:24310611}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, CC ChEBI:CHEBI:173112; EC=2.7.7.7; CC Evidence={ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20334433}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250}; CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250}; CC -!- ACTIVITY REGULATION: Regulated by alteration of quaternary structure. CC Exhibits burst rates of DNA synthesis are about 5 times faster in the CC presence of POLD4 (Pol-delta4 complex) than in its absence (Pol-delta3 CC complex), while the affinity of the enzyme for its DNA and dNTP CC substrates appears unchanged. The Pol-delta3 complex is more likely to CC proofread DNA synthesis because it cleaves single-stranded DNA twice as CC fast and transfers mismatched DNA from the polymerase to the CC exonuclease sites 9 times faster compared to the Pol-delta3 complex. CC Pol-delta3 also extends mismatched primers 3 times more slowly in the CC absence of POLD4. The conversion of Pol-delta4 into Pol-delta3 is CC induced by genotoxic stress or by replication stress leading POLD4 CC degradation (PubMed:19074196, PubMed:20334433). Stimulated in the CC presence of PCNA (PubMed:11328591, PubMed:12403614, PubMed:12522211, CC PubMed:16510448, PubMed:24022480, PubMed:24939902). This stimulation is CC further increased in the presence of KCTD13/PDIP1, most probably via CC direct interaction between KCTD13 and POLD2 (By similarity). CC {ECO:0000250|UniProtKB:P28339, ECO:0000269|PubMed:11328591, CC ECO:0000269|PubMed:12403614, ECO:0000269|PubMed:12522211, CC ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, CC ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, CC ECO:0000269|PubMed:24939902}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC Note=kcat is 87 sec(-1) for DNA synthesis by Pol-delta4 and 19 CC sec(-1) for Pol-delta3. kcat for exonuclease activity determined CC using a 26mer/40mer duplex DNA gives a value of 0.003 sec(-1) for CC Pol-delta4 and 0.026 sec(-1) for Pol-delta3. When using a 26mer/40mer CC with a T:G mismatch at the primer terminus, the switching rates from CC the polymerase to the exonuclease site for Pol-delta4 and Pol-delta3 CC are increased 20- and 10-fold, respectively, but the rate constant CC for Pol-delta3 is still 5-fold faster than that for Pol-delta4.; CC -!- SUBUNIT: Component of the tetrameric DNA polymerase delta complex (Pol- CC delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and CC POLD4/p12, with POLD1 bearing both DNA polymerase and 3' to 5' CC proofreading exonuclease activities (PubMed:11595739, PubMed:12522211, CC PubMed:17317665, PubMed:22801543). Within Pol-delta4, directly CC interacts with POLD2 and POLD4 (PubMed:11328591, PubMed:12403614, CC PubMed:16510448). Following genotoxic stress by DNA-damaging agents, CC such as ultraviolet light and methyl methanesulfonate, or by CC replication stress induced by treatment with hydroxyurea or CC aphidicolin, Pol-delta4 is converted into a trimeric form of the CC complex (Pol-delta3) by POLD4 degradation. Pol-delta3 is the major form CC at S phase replication sites and DNA damage sites (PubMed:22801543, CC PubMed:17317665). POLD1 displays different catalytic properties CC depending upon the complex it is found in (PubMed:17317665). It CC exhibits higher proofreading activity and fidelity than Pol-delta4, CC making it particularly well suited to respond to DNA damage CC (PubMed:19074196, PubMed:20334433). Directly interacts with PCNA, as do CC POLD3 and POLD4; this interaction stimulates Pol-delta4 polymerase CC activity (PubMed:11328591, PubMed:12403614, PubMed:12522211, CC PubMed:16510448, PubMed:24022480, PubMed:24939902). As POLD2 and POLD4, CC directly interacts with WRNIP1; this interaction stimulates DNA CC polymerase delta-mediated DNA synthesis, independently of the presence CC of PCNA. This stimulation may be due predominantly to an increase of CC initiation frequency and also to increased processivity CC (PubMed:15670210). 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). The DNA polymerase delta complex CC interacts with POLDIP2; this interaction is probably mediated through CC direct binding to POLD2 (PubMed:12522211). Interacts with CIAO1 CC (PubMed:23891004). Interacts with POLDIP2 (PubMed:24191025). CC {ECO:0000269|PubMed:11328591, ECO:0000269|PubMed:11595739, 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:19074196, CC ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:22801543, CC ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:24022480, CC ECO:0000269|PubMed:24191025, ECO:0000269|PubMed:24939902}. CC -!- INTERACTION: CC P28340; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-716569, EBI-10173507; CC P28340; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-716569, EBI-3867333; CC P28340; Q53G59: KLHL12; NbExp=3; IntAct=EBI-716569, EBI-740929; CC P28340; Q14847-2: LASP1; NbExp=3; IntAct=EBI-716569, EBI-9088686; CC P28340; P12004: PCNA; NbExp=3; IntAct=EBI-716569, EBI-358311; CC P28340; P49005: POLD2; NbExp=14; IntAct=EBI-716569, EBI-372354; CC P28340; Q9HCU8: POLD4; NbExp=12; IntAct=EBI-716569, EBI-864968; CC P28340; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-716569, EBI-750109; CC P28340; Q96S55: WRNIP1; NbExp=2; IntAct=EBI-716569, EBI-2513471; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11595739, CC ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:22801543}. CC Note=Colocalizes with PCNA and POLD3 at S phase replication sites CC (PubMed:11595739). After UV irradiation, recruited to DNA damage sites CC within 2 hours, independently on the cell cycle phase, nor on PCNA CC ubiquitination. This recruitment requires POLD3, PCNA and RFC1- CC replication factor C complex (PubMed:20227374, PubMed:22801543). CC {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:20227374, CC ECO:0000269|PubMed:22801543}. CC -!- TISSUE SPECIFICITY: Widely expressed, with high levels of expression in CC heart and lung. {ECO:0000269|PubMed:23770608}. CC -!- DEVELOPMENTAL STAGE: Expression is cell cycle-dependent, with highest CC levels in G2/M phase and lowest in G1. {ECO:0000269|PubMed:22801543}. CC -!- INDUCTION: Up-regulated by serum stimulation. CC {ECO:0000269|PubMed:1542570}. CC -!- DOMAIN: The CysB motif binds 1 4Fe-4S cluster and is required for the CC formation of polymerase complexes. {ECO:0000250}. CC -!- DISEASE: Colorectal cancer 10 (CRCS10) [MIM:612591]: A complex disease CC characterized by malignant lesions arising from the inner wall of the CC large intestine (the colon) and the rectum. Genetic alterations are CC often associated with progression from premalignant lesion (adenoma) to CC invasive adenocarcinoma. Risk factors for cancer of the colon and CC rectum include colon polyps, long-standing ulcerative colitis, and CC genetic family history. {ECO:0000269|PubMed:23263490, CC ECO:0000269|PubMed:24501277}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Mandibular hypoplasia, deafness, progeroid features, and CC lipodystrophy syndrome (MDPL) [MIM:615381]: An autosomal dominant CC systemic disorder characterized by prominent loss of subcutaneous fat, CC metabolic abnormalities including insulin resistance and diabetes CC mellitus, sclerodermatous skin, and a facial appearance characterized CC by mandibular hypoplasia. Sensorineural deafness occurs late in the CC first or second decades of life. {ECO:0000269|PubMed:23770608}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the DNA polymerase type-B family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/pold1/"; 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; M80397; AAA58439.1; -; mRNA. DR EMBL; M81735; AAA35768.1; -; mRNA. DR EMBL; AY129569; AAM76971.1; -; Genomic_DNA. DR EMBL; BC008800; AAH08800.1; -; mRNA. DR CCDS; CCDS12795.1; -. DR PIR; A41618; A41618. DR RefSeq; NP_001243778.1; NM_001256849.1. DR RefSeq; NP_002682.2; NM_002691.3. DR RefSeq; XP_011525340.1; XM_011527038.1. DR RefSeq; XP_016882370.1; XM_017026881.1. DR PDB; 6S1M; EM; 4.27 A; A=1-1107. DR PDB; 6S1N; EM; 4.86 A; A=1-1107. DR PDB; 6S1O; EM; 8.10 A; A=1-1107. DR PDB; 6TNY; EM; 3.08 A; A=1-1107. DR PDB; 6TNZ; EM; 4.05 A; A=1-1107. DR PDBsum; 6S1M; -. DR PDBsum; 6S1N; -. DR PDBsum; 6S1O; -. DR PDBsum; 6TNY; -. DR PDBsum; 6TNZ; -. DR AlphaFoldDB; P28340; -. DR EMDB; EMD-10080; -. DR EMDB; EMD-10081; -. DR EMDB; EMD-10082; -. DR EMDB; EMD-10539; -. DR EMDB; EMD-10540; -. DR SMR; P28340; -. DR BioGRID; 111420; 244. DR ComplexPortal; CPX-2097; DNA polymerase delta complex. DR CORUM; P28340; -. DR IntAct; P28340; 56. DR MINT; P28340; -. DR STRING; 9606.ENSP00000472445; -. DR BindingDB; P28340; -. DR ChEMBL; CHEMBL2735; -. DR DrugCentral; P28340; -. DR GlyGen; P28340; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P28340; -. DR PhosphoSitePlus; P28340; -. DR BioMuta; POLD1; -. DR DMDM; 50403732; -. DR EPD; P28340; -. DR jPOST; P28340; -. DR MassIVE; P28340; -. DR MaxQB; P28340; -. DR PaxDb; 9606-ENSP00000406046; -. DR PeptideAtlas; P28340; -. DR ProteomicsDB; 54478; -. DR Pumba; P28340; -. DR Antibodypedia; 3821; 413 antibodies from 37 providers. DR CPTC; P28340; 1 antibody. DR DNASU; 5424; -. DR Ensembl; ENST00000440232.7; ENSP00000406046.1; ENSG00000062822.16. DR Ensembl; ENST00000593887.2; ENSP00000472607.2; ENSG00000062822.16. DR Ensembl; ENST00000599857.7; ENSP00000473052.1; ENSG00000062822.16. DR Ensembl; ENST00000601098.6; ENSP00000472600.2; ENSG00000062822.16. DR Ensembl; ENST00000687454.1; ENSP00000510052.1; ENSG00000062822.16. DR GeneID; 5424; -. DR KEGG; hsa:5424; -. DR MANE-Select; ENST00000440232.7; ENSP00000406046.1; NM_002691.4; NP_002682.2. DR UCSC; uc002psb.6; human. DR AGR; HGNC:9175; -. DR CTD; 5424; -. DR DisGeNET; 5424; -. DR GeneCards; POLD1; -. DR HGNC; HGNC:9175; POLD1. DR HPA; ENSG00000062822; Low tissue specificity. DR MalaCards; POLD1; -. DR MIM; 174761; gene. DR MIM; 612591; phenotype. DR MIM; 615381; phenotype. DR neXtProt; NX_P28340; -. DR OpenTargets; ENSG00000062822; -. DR Orphanet; 440437; Familial colorectal cancer Type X. DR Orphanet; 363649; Mandibular hypoplasia-deafness-progeroid features-lipodystrophy syndrome. DR Orphanet; 447877; Polymerase proofreading-related adenomatous polyposis. DR PharmGKB; PA33496; -. DR VEuPathDB; HostDB:ENSG00000062822; -. DR eggNOG; KOG0969; Eukaryota. DR GeneTree; ENSGT00560000077365; -. DR HOGENOM; CLU_000203_2_0_1; -. DR InParanoid; P28340; -. DR OrthoDB; 211439at2759; -. DR PhylomeDB; P28340; -. DR TreeFam; TF352785; -. DR BRENDA; 2.7.7.7; 2681. DR PathwayCommons; P28340; -. 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-2564830; Cytosolic iron-sulfur cluster assembly. 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; P28340; -. DR SIGNOR; P28340; -. DR BioGRID-ORCS; 5424; 795 hits in 1163 CRISPR screens. DR ChiTaRS; POLD1; human. DR GeneWiki; POLD1; -. DR GenomeRNAi; 5424; -. DR Pharos; P28340; Tclin. DR PRO; PR:P28340; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P28340; Protein. DR Bgee; ENSG00000062822; Expressed in mucosa of transverse colon and 96 other cell types or tissues. DR ExpressionAtlas; P28340; baseline and differential. DR GO; GO:0016235; C:aggresome; IDA:HPA. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043625; C:delta DNA polymerase complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0000109; C:nucleotide-excision repair complex; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0008296; F:3'-5'-DNA exonuclease activity; IBA:GO_Central. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IMP:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro. DR GO; GO:0006287; P:base-excision repair, gap-filling; IDA:UniProtKB. DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB. DR GO; GO:0071897; P:DNA biosynthetic process; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; TAS:ProtInc. DR GO; GO:0006260; P:DNA replication; IMP:UniProtKB. DR GO; GO:0045004; P:DNA replication proofreading; IBA:GO_Central. DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IDA:UniProtKB. DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:ComplexPortal. DR GO; GO:0070987; P:error-free translesion synthesis; IDA:UniProtKB. DR GO; GO:0055089; P:fatty acid homeostasis; IMP:UniProtKB. DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; IMP:UniProtKB. DR GO; GO:0009411; P:response to UV; TAS:ProtInc. DR CDD; cd05777; DNA_polB_delta_exo; 1. DR CDD; cd05533; POLBc_delta; 1. DR Gene3D; 1.10.132.60; DNA polymerase family B, C-terminal domain; 1. DR Gene3D; 3.30.342.10; DNA Polymerase, chain B, domain 1; 1. DR Gene3D; 1.10.287.690; Helix hairpin bin; 1. DR Gene3D; 3.90.1600.10; Palm domain of DNA polymerase; 1. DR Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1. DR InterPro; IPR006172; DNA-dir_DNA_pol_B. DR InterPro; IPR017964; DNA-dir_DNA_pol_B_CS. DR InterPro; IPR006133; DNA-dir_DNA_pol_B_exonuc. DR InterPro; IPR006134; DNA-dir_DNA_pol_B_multi_dom. DR InterPro; IPR043502; DNA/RNA_pol_sf. DR InterPro; IPR042087; DNA_pol_B_thumb. DR InterPro; IPR023211; DNA_pol_palm_dom_sf. DR InterPro; IPR012337; RNaseH-like_sf. DR InterPro; IPR036397; RNaseH_sf. DR InterPro; IPR025687; Znf-C4pol. DR NCBIfam; TIGR00592; pol2; 1. DR PANTHER; PTHR10322; DNA POLYMERASE CATALYTIC SUBUNIT; 1. DR PANTHER; PTHR10322:SF23; DNA POLYMERASE DELTA CATALYTIC SUBUNIT; 1. DR Pfam; PF00136; DNA_pol_B; 1. DR Pfam; PF03104; DNA_pol_B_exo1; 1. DR Pfam; PF14260; zf-C4pol; 1. DR PRINTS; PR00106; DNAPOLB. DR SMART; SM00486; POLBc; 1. DR SUPFAM; SSF56672; DNA/RNA polymerases; 1. DR SUPFAM; SSF53098; Ribonuclease H-like; 1. DR PROSITE; PS00116; DNA_POLYMERASE_B; 1. DR Genevisible; P28340; HS. PE 1: Evidence at protein level; KW 3D-structure; 4Fe-4S; Disease variant; DNA damage; DNA excision; KW DNA repair; DNA replication; DNA-binding; DNA-directed DNA polymerase; KW Exonuclease; Hydrolase; Iron; Iron-sulfur; Isopeptide bond; Metal-binding; KW Methylation; Nuclease; Nucleotidyltransferase; Nucleus; Reference proteome; KW Transferase; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..1107 FT /note="DNA polymerase delta catalytic subunit" FT /id="PRO_0000046442" FT ZN_FING 1012..1029 FT /note="CysA-type" FT REGION 1..34 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 4..19 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOTIF 1058..1076 FT /note="CysB motif" FT COMPBIAS 19..34 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1012 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 1015 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 1026 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 1029 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250" FT BINDING 1058 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 1061 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 1071 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 1076 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT MOD_RES 19 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT CROSSLNK 574 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VARIANT 5 FT /note="R -> W (in dbSNP:rs9282830)" FT /id="VAR_048878" FT VARIANT 19 FT /note="R -> H (in dbSNP:rs3218773)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_019340" FT VARIANT 21 FT /note="G -> C (in dbSNP:rs9282831)" FT /id="VAR_048879" FT VARIANT 30 FT /note="R -> W (in dbSNP:rs3218772)" FT /evidence="ECO:0000269|PubMed:1722322, ECO:0000269|Ref.3" FT /id="VAR_016146" FT VARIANT 119 FT /note="R -> H (in dbSNP:rs1726801)" FT /evidence="ECO:0000269|PubMed:1542570, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3" FT /id="VAR_019341" FT VARIANT 145 FT /note="A -> D (found in a colorectal sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:23263490" FT /id="VAR_069333" FT VARIANT 173 FT /note="S -> N (in dbSNP:rs1726803)" FT /evidence="ECO:0000269|PubMed:1542570, ECO:0000269|Ref.3" FT /id="VAR_019342" FT VARIANT 177 FT /note="R -> H (in dbSNP:rs3218750)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_019343" FT VARIANT 347 FT /note="P -> L (in dbSNP:rs2230243)" FT /id="VAR_048880" FT VARIANT 461 FT /note="Q -> H (found in a colorectal sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:23263490" FT /id="VAR_069334" FT VARIANT 474 FT /note="L -> P (in CRCS10; dbSNP:rs587777627)" FT /evidence="ECO:0000269|PubMed:24501277" FT /id="VAR_071966" FT VARIANT 478 FT /note="S -> N (risk factor for CRCS10; dbSNP:rs397514632)" FT /evidence="ECO:0000269|PubMed:23263490" FT /id="VAR_069335" FT VARIANT 605 FT /note="Missing (in MDPL; the mutant enzyme lacks DNA FT polymerase ability; has decreased exonuclease activity; can FT bind DNA but is unable to interact with and incorporate FT dNTPs)" FT /evidence="ECO:0000269|PubMed:23770608" FT /id="VAR_070231" FT VARIANT 787 FT /note="P -> L (found in a colorectal sample; somatic FT mutation; dbSNP:rs199783227)" FT /evidence="ECO:0000269|PubMed:23263490" FT /id="VAR_069336" FT VARIANT 808 FT /note="R -> H (found in a colorectal sample; somatic FT mutation; dbSNP:rs771700024)" FT /evidence="ECO:0000269|PubMed:23263490" FT /id="VAR_069337" FT VARIANT 849 FT /note="R -> H (in dbSNP:rs3218775)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_019344" FT VARIANT 864 FT /note="A -> T (found in a colorectal sample; somatic FT mutation; dbSNP:rs765437818)" FT /evidence="ECO:0000269|PubMed:23263490" FT /id="VAR_069338" FT VARIANT 1086 FT /note="R -> Q (in dbSNP:rs3219457)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_019345" FT MUTAGEN 402 FT /note="D->A: Loss of exonuclease activity. No effect on DNA FT polymerase activity." FT /evidence="ECO:0000269|PubMed:19074196, FT ECO:0000269|PubMed:20334433" FT CONFLICT 472 FT /note="Y -> H (in Ref. 1; AAA58439)" FT /evidence="ECO:0000305" FT CONFLICT 776 FT /note="R -> G (in Ref. 2; AAA35768)" FT /evidence="ECO:0000305" FT TURN 89..91 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 94..105 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 123..134 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 136..142 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 147..151 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 154..157 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 161..168 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 174..176 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 177..179 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 180..183 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 192..195 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 197..200 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 207..213 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 217..219 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 220..227 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 228..230 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 234..238 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 250..258 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 265..268 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 285..291 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 296..298 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 302..305 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 311..319 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 329..331 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 334..343 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 346..348 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 350..358 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 366..370 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 374..388 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 391..397 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 398..401 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 402..412 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 416..419 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 422..424 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 431..438 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 439..441 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 442..449 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 455..458 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 459..466 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 474..481 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 494..498 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 502..525 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 528..539 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 545..547 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 552..563 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 564..567 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 592..594 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 598..605 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 606..613 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 618..620 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 624..629 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 634..636 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 637..639 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 641..643 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 645..647 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 649..651 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 656..674 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 680..704 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 707..710 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 714..738 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 741..744 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 745..747 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 750..762 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 768..782 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 784..786 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 792..805 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 808..819 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 824..829 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 830..832 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 834..836 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 838..852 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 857..872 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 878..881 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 883..886 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 890..894 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 899..905 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 920..927 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 937..940 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 942..948 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 954..959 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 960..962 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 963..970 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 977..989 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 1002..1004 FT /evidence="ECO:0007829|PDB:6TNY" FT TURN 1013..1015 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 1020..1022 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 1034..1055 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 1057..1062 FT /evidence="ECO:0007829|PDB:6TNY" FT STRAND 1065..1067 FT /evidence="ECO:0007829|PDB:6TNY" FT HELIX 1078..1095 FT /evidence="ECO:0007829|PDB:6TNY" SQ SEQUENCE 1107 AA; 123631 MW; 9D04D34AB4AEE810 CRC64; MDGKRRPGPG PGVPPKRARG GLWDDDDAPR PSQFEEDLAL MEEMEAEHRL QEQEEEELQS VLEGVADGQV PPSAIDPRWL RPTPPALDPQ TEPLIFQQLE IDHYVGPAQP VPGGPPPSRG SVPVLRAFGV TDEGFSVCCH IHGFAPYFYT PAPPGFGPEH MGDLQRELNL AISRDSRGGR ELTGPAVLAV ELCSRESMFG YHGHGPSPFL RITVALPRLV APARRLLEQG IRVAGLGTPS FAPYEANVDF EIRFMVDTDI VGCNWLELPA GKYALRLKEK ATQCQLEADV LWSDVVSHPP EGPWQRIAPL RVLSFDIECA GRKGIFPEPE RDPVIQICSL GLRWGEPEPF LRLALTLRPC APILGAKVQS YEKEEDLLQA WSTFIRIMDP DVITGYNIQN FDLPYLISRA QTLKVQTFPF LGRVAGLCSN IRDSSFQSKQ TGRRDTKVVS MVGRVQMDML QVLLREYKLR SYTLNAVSFH FLGEQKEDVQ HSIITDLQNG NDQTRRRLAV YCLKDAYLPL RLLERLMVLV NAVEMARVTG VPLSYLLSRG QQVKVVSQLL RQAMHEGLLM PVVKSEGGED YTGATVIEPL KGYYDVPIAT LDFSSLYPSI MMAHNLCYTT LLRPGTAQKL GLTEDQFIRT PTGDEFVKTS VRKGLLPQIL ENLLSARKRA KAELAKETDP LRRQVLDGRQ LALKVSANSV YGFTGAQVGK LPCLEISQSV TGFGRQMIEK TKQLVESKYT VENGYSTSAK VVYGDTDSVM CRFGVSSVAE AMALGREAAD WVSGHFPSPI RLEFEKVYFP YLLISKKRYA GLLFSSRPDA HDRMDCKGLE AVRRDNCPLV ANLVTASLRR LLIDRDPEGA VAHAQDVISD LLCNRIDISQ LVITKELTRA ASDYAGKQAH VELAERMRKR DPGSAPSLGD RVPYVIISAA KGVAAYMKSE DPLFVLEHSL PIDTQYYLEQ QLAKPLLRIF EPILGEGRAE AVLLRGDHTR CKTVLTGKVG GLLAFAKRRN CCIGCRTVLS HQGAVCEFCQ PRESELYQKE VSHLNALEER FSRLWTQCQR CQGSLHEDVI CTSRDCPIFY MRKKVRKDLE DQEQLLRRFG PPGPEAW //