ID   DPOD4_MOUSE             Reviewed;         107 AA.
AC   Q9CWP8;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   24-JAN-2024, entry version 146.
DE   RecName: Full=DNA polymerase delta subunit 4;
DE   AltName: Full=DNA polymerase delta subunit p12;
GN   Name=Pold4;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Mammary gland;
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   [3]
RP   UBIQUITINATION BY RNF8, AND INDUCTION BY UV AND ALKYLATING AGENT.
RX   PubMed=23233665; DOI=10.1074/jbc.m112.423392;
RA   Zhang S., Zhou Y., Sarkeshik A., Yates J.R. III, Thomson T.M., Zhang Z.,
RA   Lee E.Y., Lee M.Y.;
RT   "Identification of RNF8 as a ubiquitin ligase involved in targeting the p12
RT   subunit of DNA polymerase delta for degradation in response to DNA
RT   damage.";
RL   J. Biol. Chem. 288:2941-2950(2013).
CC   -!- FUNCTION: As a component of the tetrameric DNA polymerase delta complex
CC       (Pol-delta4), plays a role in high fidelity genome replication and
CC       repair. Within this complex, increases the rate of DNA synthesis and
CC       decreases fidelity by regulating POLD1 polymerase and proofreading 3'
CC       to 5' exonuclease activity. Pol-delta4 participates in Okazaki fragment
CC       processing, through both the short flap pathway, as well as a nick
CC       translation system. Under conditions of DNA replication stress,
CC       required for the repair of broken replication forks through break-
CC       induced replication (BIR), a mechanism that may induce segmental
CC       genomic duplications of up to 200 kb. Involved in Pol-delta4
CC       translesion synthesis (TLS) of templates carrying O6-methylguanine or
CC       abasic sites. Its degradation in response to DNA damage is required for
CC       the inhibition of fork progression and cell survival.
CC       {ECO:0000250|UniProtKB:Q9HCU8}.
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 DNA polymerase and 3' to 5' proofreading
CC       exonuclease activities. Within this complex, directly interacts with
CC       POLD1 and POLD2. Directly interacts with PCNA, as do POLD1 and POLD3;
CC       this interaction stimulates Pol-delta4 polymerase activity. As POLD1
CC       and POLD2, directly interacts with WRNIP1; this interaction stimulates
CC       DNA polymerase delta-mediated DNA synthesis, independently of the
CC       presence of PCNA, possibly by increasing initiation frequency. Upon
CC       genotoxic stress induced by DNA damaging agents or by replication
CC       stress, POLD4 is proteolytically degraded and Pol-delta4 is converted
CC       into a trimeric form of the complex (Pol-delta3) that has an increased
CC       proofreading activity. The DNA polymerase delta complex interacts with
CC       POLDIP2; this interaction is probably mediated through direct binding
CC       to POLD2. {ECO:0000250|UniProtKB:Q9HCU8}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9HCU8}.
CC       Note=Partially recruited to DNA damage sites within 2 hours following
CC       UV irradiation, before degradation. {ECO:0000250|UniProtKB:Q9HCU8}.
CC   -!- INDUCTION: In response to DNA damage or genotoxic stress, such as UV
CC       irradiation or treatment with an alkylating agent, protein expression
CC       drastically drops. {ECO:0000269|PubMed:23233665}.
CC   -!- PTM: Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination in
CC       response to UV irradiation or treatment with an alkylating agent,
CC       leading to proteasomal degradation. This modification is mediated, at
CC       least in part, by RNF8. {ECO:0000269|PubMed:23233665}.
CC   -!- PTM: Ubiquitinated; undergoes 'Lys-48'-linked ubiquitination in
CC       response to UV irradiation, leading to proteasomal degradation. This
CC       modification is partly mediated by RNF8 and by the DCX(DTL) E3
CC       ubiquitin ligase complex (also called CRL4(CDT2)). Efficient
CC       degradation requires the presence of PCNA and is required for the
CC       inhibition of fork progression after DNA damage.
CC       {ECO:0000250|UniProtKB:Q9HCU8}.
CC   -!- SIMILARITY: Belongs to the DNA polymerase delta subunit 4 family.
CC       {ECO:0000305}.
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DR   EMBL; AK010477; BAB26970.1; -; mRNA.
DR   EMBL; BC028520; AAH28520.1; -; mRNA.
DR   CCDS; CCDS29424.1; -.
DR   RefSeq; NP_081472.1; NM_027196.4.
DR   AlphaFoldDB; Q9CWP8; -.
DR   SMR; Q9CWP8; -.
DR   ComplexPortal; CPX-2098; DNA polymerase delta complex.
DR   CORUM; Q9CWP8; -.
DR   STRING; 10090.ENSMUSP00000025773; -.
DR   PhosphoSitePlus; Q9CWP8; -.
DR   MaxQB; Q9CWP8; -.
DR   PaxDb; 10090-ENSMUSP00000025773; -.
DR   ProteomicsDB; 277388; -.
DR   DNASU; 69745; -.
DR   Ensembl; ENSMUST00000025773.5; ENSMUSP00000025773.4; ENSMUSG00000024854.5.
DR   GeneID; 69745; -.
DR   KEGG; mmu:69745; -.
DR   UCSC; uc008fzm.2; mouse.
DR   AGR; MGI:1916995; -.
DR   CTD; 57804; -.
DR   MGI; MGI:1916995; Pold4.
DR   VEuPathDB; HostDB:ENSMUSG00000024854; -.
DR   eggNOG; ENOG502SC9I; Eukaryota.
DR   GeneTree; ENSGT00390000005096; -.
DR   HOGENOM; CLU_132157_0_0_1; -.
DR   InParanoid; Q9CWP8; -.
DR   OMA; DPRFQYS; -.
DR   OrthoDB; 276347at2759; -.
DR   PhylomeDB; Q9CWP8; -.
DR   TreeFam; TF103004; -.
DR   Reactome; R-MMU-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR   Reactome; R-MMU-174411; Polymerase switching on the C-strand of the telomere.
DR   Reactome; R-MMU-174414; Processive synthesis on the C-strand of the telomere.
DR   Reactome; R-MMU-174417; Telomere C-strand (Lagging Strand) Synthesis.
DR   Reactome; R-MMU-174437; Removal of the Flap Intermediate from the C-strand.
DR   Reactome; R-MMU-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR   Reactome; R-MMU-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR   Reactome; R-MMU-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR   Reactome; R-MMU-5656169; Termination of translesion DNA synthesis.
DR   Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR).
DR   Reactome; R-MMU-5696397; Gap-filling DNA repair synthesis and ligation in GG-NER.
DR   Reactome; R-MMU-5696400; Dual Incision in GG-NER.
DR   Reactome; R-MMU-6782135; Dual incision in TC-NER.
DR   Reactome; R-MMU-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR   Reactome; R-MMU-69091; Polymerase switching.
DR   Reactome; R-MMU-69166; Removal of the Flap Intermediate.
DR   Reactome; R-MMU-69183; Processive synthesis on the lagging strand.
DR   BioGRID-ORCS; 69745; 0 hits in 114 CRISPR screens.
DR   PRO; PR:Q9CWP8; -.
DR   Proteomes; UP000000589; Chromosome 19.
DR   RNAct; Q9CWP8; Protein.
DR   Bgee; ENSMUSG00000024854; Expressed in spleen and 70 other cell types or tissues.
DR   ExpressionAtlas; Q9CWP8; baseline and differential.
DR   GO; GO:0043625; C:delta DNA polymerase complex; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0000731; P:DNA synthesis involved in DNA repair; IBA:GO_Central.
DR   GO; GO:0006261; P:DNA-templated DNA replication; ISO:MGI.
DR   GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:MGI.
DR   InterPro; IPR007218; DNA_pol_delta_4.
DR   PANTHER; PTHR14303; DNA POLYMERASE DELTA SUBUNIT 4; 1.
DR   PANTHER; PTHR14303:SF0; DNA POLYMERASE DELTA SUBUNIT 4; 1.
DR   Pfam; PF04081; DNA_pol_delta_4; 1.
DR   Genevisible; Q9CWP8; MM.
PE   1: Evidence at protein level;
KW   DNA damage; DNA excision; DNA repair; DNA replication; Nucleus;
KW   Reference proteome; Ubl conjugation.
FT   CHAIN           1..107
FT                   /note="DNA polymerase delta subunit 4"
FT                   /id="PRO_0000186052"
FT   REGION          1..40
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           1..16
FT                   /note="PCNA-interaction protein motif (PIP box)"
FT                   /evidence="ECO:0000250|UniProtKB:Q9HCU8"
FT   COMPBIAS        1..30
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   107 AA;  12403 MW;  14A27054D4E7511E CRC64;
     MGRKRFITDS YPVVKKREGP PGHSKGELAP ELGEDTQSLS QEETELELLR QFDLAWQYGP
     CTGITRLQRW SRAEQMGLKP PLEVYQVLKA HPEDPHFQCS LWHLYPL
//