DPOD1_HUMAN
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 03-AUG-2022, entry version 215.
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 VARIANT CRCS10 ASN-478, AND VARIANTS ASP-145; HIS-461; LEU-787; HIS-808 AND
RP THR-864.
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 sec(-
CC 1) for Pol-delta3. kcat for exonuclease activity determined using a
CC 26mer/40mer duplex DNA gives a value of 0.003 sec(-1) for Pol-delta4
CC and 0.026 sec(-1) for Pol-delta3. When using a 26mer/40mer with a T:G
CC mismatch at the primer terminus, the switching rates from the
CC polymerase to the exonuclease site for Pol-delta4 and Pol-delta3 are
CC increased 20- and 10-fold, respectively, but the rate constant for
CC 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 ---------------------------------------------------------------------------
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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 SMR; P28340; -.
DR BioGRID; 111420; 208.
DR ComplexPortal; CPX-2097; DNA polymerase delta complex.
DR CORUM; P28340; -.
DR IntAct; P28340; 54.
DR MINT; P28340; -.
DR STRING; 9606.ENSP00000406046; -.
DR BindingDB; P28340; -.
DR ChEMBL; CHEMBL2735; -.
DR DrugCentral; P28340; -.
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; P28340; -.
DR PeptideAtlas; P28340; -.
DR PRIDE; P28340; -.
DR ProteomicsDB; 54478; -.
DR Antibodypedia; 3821; 369 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 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; 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 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; 779 hits in 1085 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 94 other tissues.
DR ExpressionAtlas; P28340; baseline and differential.
DR Genevisible; P28340; HS.
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'-exodeoxyribonuclease 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 Gene3D; 1.10.132.60; -; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR Gene3D; 3.90.1600.10; -; 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 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; SSF53098; SSF53098; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS00116; DNA_POLYMERASE_B; 1.
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 (in CRCS10; associated with disease
FT susceptibility; 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
