PRIPO_HUMAN
ID PRIPO_HUMAN Reviewed; 560 AA.
AC Q96LW4; A0A0A0MTC0; D3DP55; D6RDM1; Q5HYJ9;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 28-MAR-2018, sequence version 3.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=DNA-directed primase/polymerase protein {ECO:0000303|PubMed:24126761};
DE Short=hPrimpol1 {ECO:0000303|PubMed:24126761};
DE EC=2.7.7.- {ECO:0000269|PubMed:25262353, ECO:0000269|PubMed:25746449, ECO:0000269|PubMed:27989484, ECO:0000269|PubMed:28534480, ECO:0000269|PubMed:30633872, ECO:0000269|PubMed:30889508};
DE AltName: Full=Coiled-coil domain-containing protein 111 {ECO:0000303|PubMed:23579484};
GN Name=PRIMPOL {ECO:0000303|PubMed:24126761, ECO:0000312|HGNC:HGNC:26575};
GN Synonyms=CCDC111 {ECO:0000303|PubMed:23579484};
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Adipose tissue;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [7]
RP FUNCTION, INTERACTION WITH RPA1, AND MUTAGENESIS OF ASP-114; HIS-169 AND
RP HIS-426.
RX PubMed=24126761; DOI=10.1038/embor.2013.159;
RA Wan L., Lou J., Xia Y., Su B., Liu T., Cui J., Sun Y., Lou H., Huang J.;
RT "hPrimpol1/CCDC111 is a human DNA primase-polymerase required for the
RT maintenance of genome integrity.";
RL EMBO Rep. 14:1104-1112(2013).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, COFACTOR, AND MUTAGENESIS OF
RP 114-ASP--GLU-116.
RX PubMed=24207056; DOI=10.1016/j.molcel.2013.09.025;
RA Garcia-Gomez S., Reyes A., Martinez-Jimenez M.I., Chocron E.S., Mouron S.,
RA Terrados G., Powell C., Salido E., Mendez J., Holt I.J., Blanco L.;
RT "PrimPol, an archaic primase/polymerase operating in human cells.";
RL Mol. Cell 52:541-553(2013).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF 114-ASP--GLU-116.
RX PubMed=24267451; DOI=10.1016/j.molcel.2013.10.035;
RA Bianchi J., Rudd S.G., Jozwiakowski S.K., Bailey L.J., Soura V., Taylor E.,
RA Stevanovic I., Green A.J., Stracker T.H., Lindsay H.D., Doherty A.J.;
RT "PrimPol bypasses UV photoproducts during eukaryotic chromosomal DNA
RT replication.";
RL Mol. Cell 52:566-573(2013).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-419 AND HIS-426.
RX PubMed=24240614; DOI=10.1038/nsmb.2719;
RA Mouron S., Rodriguez-Acebes S., Martinez-Jimenez M.I., Garcia-Gomez S.,
RA Chocron S., Blanco L., Mendez J.;
RT "Repriming of DNA synthesis at stalled replication forks by human
RT PrimPol.";
RL Nat. Struct. Mol. Biol. 20:1383-1389(2013).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=25255211; DOI=10.1021/bi501024u;
RA Zafar M.K., Ketkar A., Lodeiro M.F., Cameron C.E., Eoff R.L.;
RT "Kinetic analysis of human PrimPol DNA polymerase activity reveals a
RT generally error-prone enzyme capable of accurately bypassing 7,8-dihydro-8-
RT oxo-2'-deoxyguanosine.";
RL Biochemistry 53:6584-6594(2014).
RN [13]
RP DOMAIN, FUNCTION, AND MUTAGENESIS OF 114-ASP--GLU-116; CYS-419 AND HIS-426.
RX PubMed=24682820; DOI=10.1093/nar/gku214;
RA Keen B.A., Jozwiakowski S.K., Bailey L.J., Bianchi J., Doherty A.J.;
RT "Molecular dissection of the domain architecture and catalytic activities
RT of human PrimPol.";
RL Nucleic Acids Res. 42:5830-5845(2014).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF VARIANT MYP22 ASP-89, AND
RP MUTAGENESIS OF TYR-89.
RX PubMed=25262353; DOI=10.1093/nar/gku879;
RA Keen B.A., Bailey L.J., Jozwiakowski S.K., Doherty A.J.;
RT "Human PrimPol mutation associated with high myopia has a DNA replication
RT defect.";
RL Nucleic Acids Res. 42:12102-12111(2014).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=25746449; DOI=10.1016/j.dnarep.2015.02.013;
RA Martinez-Jimenez M.I., Garcia-Gomez S., Bebenek K., Sastre-Moreno G.,
RA Calvo P.A., Diaz-Talavera A., Kunkel T.A., Blanco L.;
RT "Alternative solutions and new scenarios for translesion DNA synthesis by
RT human PrimPol.";
RL DNA Repair 29:127-138(2015).
RN [16]
RP COMMENT ON PUBMED:25262353 RESULTS.
RX PubMed=25680975; DOI=10.1167/iovs.14-16072;
RA Li J., Zhang Q.;
RT "PRIMPOL mutation: functional study does not always reveal the truth.";
RL Invest. Ophthalmol. Vis. Sci. 56:1181-1182(2015).
RN [17]
RP COMMENT ON PUBMED:25680975.
RX PubMed=25680976; DOI=10.1167/iovs.14-16123;
RA Keen B.A., Bailey L.J., Jozwiakowski S.K., Doherty A.J.;
RT "Author response: PRIMPOL mutation: functional study does not always reveal
RT the truth.";
RL Invest. Ophthalmol. Vis. Sci. 56:1183-1183(2015).
RN [18]
RP FUNCTION, AND INTERACTION WITH RPA1 AND SSBP1.
RX PubMed=25550423; DOI=10.1093/nar/gku1321;
RA Guilliam T.A., Jozwiakowski S.K., Ehlinger A., Barnes R.P., Rudd S.G.,
RA Bailey L.J., Skehel J.M., Eckert K.A., Chazin W.J., Doherty A.J.;
RT "Human PrimPol is a highly error-prone polymerase regulated by single-
RT stranded DNA binding proteins.";
RL Nucleic Acids Res. 43:1056-1068(2015).
RN [19]
RP FUNCTION, AND MUTAGENESIS OF 114-ASP--GLU-116; CYS-419 AND HIS-426.
RX PubMed=26626482; DOI=10.1016/j.molcel.2015.10.038;
RA Schiavone D., Jozwiakowski S.K., Romanello M., Guilbaud G., Guilliam T.A.,
RA Bailey L.J., Sale J.E., Doherty A.J.;
RT "PrimPol is required for replicative tolerance of G quadruplexes in
RT vertebrate cells.";
RL Mol. Cell 61:161-169(2016).
RN [20]
RP INTERACTION WITH POLDIP2.
RX PubMed=26984527; DOI=10.1093/nar/gkw175;
RA Guilliam T.A., Bailey L.J., Brissett N.C., Doherty A.J.;
RT "PolDIP2 interacts with human PrimPol and enhances its DNA polymerase
RT activities.";
RL Nucleic Acids Res. 44:3317-3329(2016).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=27989484; DOI=10.1016/j.dnarep.2016.11.003;
RA Tokarsky E.J., Wallenmeyer P.C., Phi K.K., Suo Z.;
RT "Significant impact of divalent metal ions on the fidelity, sugar
RT selectivity, and drug incorporation efficiency of human PrimPol.";
RL DNA Repair 49:51-59(2017).
RN [22]
RP INTERACTION WITH RPA1.
RX PubMed=28396594; DOI=10.1038/s41598-017-00958-3;
RA Martinez-Jimenez M.I., Lahera A., Blanco L.;
RT "Human PrimPol activity is enhanced by RPA.";
RL Sci. Rep. 7:783-783(2017).
RN [23]
RP FUNCTION, AND MUTAGENESIS OF 114-ASP--GLU-116; CYS-419 AND HIS-426.
RX PubMed=30478192; DOI=10.15252/embj.201899793;
RA Svikovic S., Crisp A., Tan-Wong S.M., Guilliam T.A., Doherty A.J.,
RA Proudfoot N.J., Guilbaud G., Sale J.E.;
RT "R-loop formation during S phase is restricted by PrimPol-mediated
RT repriming.";
RL EMBO J. 38:0-0(2019).
RN [24]
RP DOMAIN, FUNCTION, AND MUTAGENESIS OF 114-ASP--GLU-116.
RX PubMed=29608762; DOI=10.1093/nar/gky230;
RA Martinez-Jimenez M.I., Calvo P.A., Garcia-Gomez S., Guerra-Gonzalez S.,
RA Blanco L.;
RT "The Zn-finger domain of human PrimPol is required to stabilize the
RT initiating nucleotide during DNA priming.";
RL Nucleic Acids Res. 46:4138-4151(2018).
RN [25]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, DOMAIN, AND MUTAGENESIS OF
RP 114-ASP--GLU-116 AND ASP-280.
RX PubMed=30889508; DOI=10.1016/j.dnarep.2019.03.006;
RA Calvo P.A., Sastre-Moreno G., Perpina C., Guerra S., Martinez-Jimenez M.I.,
RA Blanco L.;
RT "The invariant glutamate of human PrimPol DxE motif is critical for its
RT Mn2+-dependent distinctive activities.";
RL DNA Repair 77:65-75(2019).
RN [26]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=30633872; DOI=10.1016/j.jmb.2019.01.002;
RA Xu W., Zhao W., Morehouse N., Tree M.O., Zhao L.;
RT "Divalent cations alter the rate-limiting step of PrimPol-catalyzed DNA
RT elongation.";
RL J. Mol. Biol. 431:673-686(2019).
RN [27]
RP FUNCTION.
RX PubMed=31676232; DOI=10.1016/j.molcel.2019.10.008;
RA Quinet A., Tirman S., Jackson J., Svikovic S., Lemacon D.,
RA Carvajal-Maldonado D., Gonzalez-Acosta D., Vessoni A.T., Cybulla E.,
RA Wood M., Tavis S., Batista L.F.Z., Mendez J., Sale J.E., Vindigni A.;
RT "PRIMPOL-mediated adaptive response suppresses replication fork reversal in
RT BRCA-deficient cells.";
RL Mol. Cell 0:0-0(2019).
RN [28]
RP FUNCTION.
RX PubMed=30715459; DOI=10.1093/nar/gkz056;
RA Bailey L.J., Bianchi J., Doherty A.J.;
RT "PrimPol is required for the maintenance of efficient nuclear and
RT mitochondrial DNA replication in human cells.";
RL Nucleic Acids Res. 47:4026-4038(2019).
RN [29] {ECO:0007744|PDB:5L2X}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-353 IN COMPLEX WITH
RP 2'-DEOXYADENOSINE 5'-TRIPHOSPHATE AND CALCIUM.
RX PubMed=27819052; DOI=10.1126/sciadv.1601317;
RA Rechkoblit O., Gupta Y.K., Malik R., Rajashankar K.R., Johnson R.E.,
RA Prakash L., Prakash S., Aggarwal A.K.;
RT "Structure and mechanism of human PrimPol, a DNA polymerase with primase
RT activity.";
RL Sci. Adv. 2:e1601317-e1601317(2016).
RN [30] {ECO:0007744|PDB:5N85, ECO:0007744|PDB:5N8A}
RP X-RAY CRYSTALLOGRAPHY (1.28 ANGSTROMS) OF 480-560 IN COMPLEX WITH RPA1,
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, RPA1-BINDING MOTIF, AND
RP MUTAGENESIS OF 519-ASP--PHE-522 AND 551-ASP--ILE-554.
RX PubMed=28534480; DOI=10.1038/ncomms15222;
RA Guilliam T.A., Brissett N.C., Ehlinger A., Keen B.A., Kolesar P.,
RA Taylor E.M., Bailey L.J., Lindsay H.D., Chazin W.J., Doherty A.J.;
RT "Molecular basis for PrimPol recruitment to replication forks by RPA.";
RL Nat. Commun. 8:15222-15222(2017).
RN [31]
RP VARIANT MYP22 ASP-89.
RX PubMed=23579484; DOI=10.1007/s00439-013-1303-6;
RA Zhao F., Wu J., Xue A., Su Y., Wang X., Lu X., Zhou Z., Qu J., Zhou X.;
RT "Exome sequencing reveals CCDC111 mutation associated with high myopia.";
RL Hum. Genet. 132:913-921(2013).
CC -!- FUNCTION: DNA primase and DNA polymerase required to tolerate
CC replication-stalling lesions by bypassing them (PubMed:24126761,
CC PubMed:24207056, PubMed:24240614, PubMed:24267451, PubMed:25255211,
CC PubMed:24682820, PubMed:25262353, PubMed:25746449, PubMed:25550423,
CC PubMed:27989484, PubMed:29608762, PubMed:30889508, PubMed:28534480).
CC Required to facilitate mitochondrial and nuclear replication fork
CC progression by initiating de novo DNA synthesis using dNTPs and acting
CC as an error-prone DNA polymerase able to bypass certain DNA lesions
CC (PubMed:24126761, PubMed:24207056, PubMed:24240614, PubMed:24267451,
CC PubMed:25255211, PubMed:24682820, PubMed:25262353, PubMed:25746449,
CC PubMed:25550423, PubMed:27989484, PubMed:29608762, PubMed:30889508,
CC PubMed:30633872, PubMed:28534480). Shows a high capacity to tolerate
CC DNA damage lesions such as 8oxoG and abasic sites in DNA
CC (PubMed:24126761, PubMed:24207056, PubMed:24240614, PubMed:24267451,
CC PubMed:25746449). Provides different translesion synthesis alternatives
CC when DNA replication is stalled: able to synthesize DNA primers
CC downstream of lesions, such as ultraviolet (UV) lesions, R-loops and G-
CC quadruplexes, to allow DNA replication to continue (PubMed:24240614,
CC PubMed:26626482, PubMed:28534480, PubMed:30478192). Can also realign
CC primers ahead of 'unreadable lesions' such as abasic sites and 6-4
CC photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion
CC (PubMed:25746449). Also able to incorporate nucleotides opposite DNA
CC lesions such as 8oxoG, like a regular translesion synthesis DNA
CC polymerase (PubMed:24207056, PubMed:25255211, PubMed:25746449). Also
CC required for reinitiating stalled forks after UV damage during nuclear
CC DNA replication (PubMed:24240614). Required for mitochondrial DNA
CC (mtDNA) synthesis and replication, by reinitiating synthesis after UV
CC damage or in the presence of chain-terminating nucleotides
CC (PubMed:24207056). Prevents APOBEC family-mediated DNA mutagenesis by
CC repriming downstream of abasic site to prohibit error-prone translesion
CC synthesis (By similarity). Has non-overlapping function with POLH
CC (PubMed:24240614). In addition to its role in DNA damage response, also
CC required to maintain efficient nuclear and mitochondrial DNA
CC replication in unperturbed cells (PubMed:30715459).
CC {ECO:0000250|UniProtKB:Q6P1E7, ECO:0000269|PubMed:24126761,
CC ECO:0000269|PubMed:24207056, ECO:0000269|PubMed:24240614,
CC ECO:0000269|PubMed:24267451, ECO:0000269|PubMed:24682820,
CC ECO:0000269|PubMed:25255211, ECO:0000269|PubMed:25262353,
CC ECO:0000269|PubMed:25550423, ECO:0000269|PubMed:25746449,
CC ECO:0000269|PubMed:26626482, ECO:0000269|PubMed:27989484,
CC ECO:0000269|PubMed:28534480, ECO:0000269|PubMed:29608762,
CC ECO:0000269|PubMed:30478192, ECO:0000269|PubMed:30633872,
CC ECO:0000269|PubMed:30715459, ECO:0000269|PubMed:30889508}.
CC -!- FUNCTION: Involved in adaptive response to cisplatin, a
CC chemotherapeutic that causes reversal of replication forks, in cancer
CC cells: reinitiates DNA synthesis past DNA lesions in BRCA1-deficient
CC cancer cells treated with cisplatin via its de novo priming activity
CC (PubMed:31676232). Repriming rescues fork degradation while leading to
CC accumulation of internal ssDNA gaps behind the forks (PubMed:31676232).
CC ATR regulates adaptive response to cisplatin (PubMed:31676232).
CC {ECO:0000269|PubMed:31676232}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:25255211, ECO:0000269|PubMed:25746449,
CC ECO:0000269|PubMed:27989484, ECO:0000269|PubMed:30633872,
CC ECO:0000269|PubMed:30889508, ECO:0000305|PubMed:24207056};
CC Note=Can act both with Mn(2+) and Mg(2+) as cofactor in vitro, but
CC Mn(2+) is the preferred cofactor in vivo (PubMed:25255211,
CC PubMed:25746449, PubMed:27989484, PubMed:30889508, PubMed:30633872).
CC The polymerase activity incorporates correct dNTPs with much higher
CC efficiency with Mn(2+) than with Mg(2+) (PubMed:25255211,
CC PubMed:30889508). The fidelity is slightly more accurate when Mg(2+) is
CC the cofactor compared to Mn(2+) (PubMed:25255211, PubMed:30889508). In
CC the presence of Mn(2+), a conformational transition step from non-
CC productive to productive PRIMPOL:DNA complexes limits the enzymatic
CC turnover, whereas in the presence of Mg(2+), the chemical step becomes
CC rate limiting (PubMed:30633872). {ECO:0000269|PubMed:25255211,
CC ECO:0000269|PubMed:25746449, ECO:0000269|PubMed:27989484,
CC ECO:0000269|PubMed:30633872, ECO:0000269|PubMed:30889508};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14 uM for dTTP (in presence of 2 mM of Mn(2+)
CC {ECO:0000269|PubMed:30633872};
CC KM=24 uM for dTTP (in presence of 50 uM of Mn(2+)
CC {ECO:0000269|PubMed:30633872};
CC KM=430 uM for dTTP (in presence of 2 mM of Mg(2+)
CC {ECO:0000269|PubMed:30633872};
CC Note=kcat is 0.05 sec(-1) for dTTP (in presence of 2 mM of Mn(2+).
CC kcat is 0.02 sec(-1) for dTTP (in presence of 50 uM of Mn(2+). kcat
CC is 0.01 sec(-1) for dTTP (in presence of 2 mM of Mg(2+).;
CC -!- SUBUNIT: Interacts with RPA1; leading to recruitment to chromatin and
CC stimulate DNA primase activity (PubMed:24126761, PubMed:25550423,
CC PubMed:28396594, PubMed:28534480). Interacts with SSBP1
CC (PubMed:25550423). Interacts with POLDIP2; leading to enhance DNA
CC polymerase activity (PubMed:26984527). {ECO:0000269|PubMed:24126761,
CC ECO:0000269|PubMed:25550423, ECO:0000269|PubMed:26984527,
CC ECO:0000269|PubMed:28396594, ECO:0000269|PubMed:28534480}.
CC -!- INTERACTION:
CC Q96LW4; P55273: CDKN2D; NbExp=3; IntAct=EBI-10044038, EBI-745859;
CC Q96LW4; Q00013: MPP1; NbExp=3; IntAct=EBI-10044038, EBI-711788;
CC Q96LW4; Q8NEY1-3: NAV1; NbExp=5; IntAct=EBI-10044038, EBI-11953718;
CC Q96LW4; P25786: PSMA1; NbExp=3; IntAct=EBI-10044038, EBI-359352;
CC Q96LW4; P27694: RPA1; NbExp=7; IntAct=EBI-10044038, EBI-621389;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24207056,
CC ECO:0000269|PubMed:24240614}. Mitochondrion matrix
CC {ECO:0000269|PubMed:24207056}. Chromosome
CC {ECO:0000269|PubMed:28534480}. Note=Present in the nucleus, but a
CC larger fraction is localized inside mitochondria (PubMed:24207056).
CC Associates with nuclear chromatin during the G1 and S phases of
CC unperturbed cell cycles (PubMed:24207056). Recruited to stalled
CC replication forks following interaction with RPA1 (PubMed:28534480).
CC {ECO:0000269|PubMed:24207056, ECO:0000269|PubMed:28534480}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96LW4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96LW4-2; Sequence=VSP_053600;
CC -!- DOMAIN: The zinc knuckle motif binds zinc and is required for the DNA
CC primase activity (PubMed:24682820, PubMed:29608762). It facilitates the
CC binding and selection of the 5'-nucleotide of the newly synthesized
CC primer and the recognition of preferred initiation sites
CC (PubMed:29608762). {ECO:0000269|PubMed:24682820,
CC ECO:0000269|PubMed:29608762}.
CC -!- DOMAIN: The RPA1-binding motifs (RBM) mediate interaction with RPA1 and
CC are essential for recruitment to chromatin (PubMed:28534480). The
CC interaction is primarily mediated by RPA1-binding motif 1, which binds
CC to the basic cleft of RPA1, with motif 2 plays a supporting role in
CC RPA1-binding (PubMed:28534480). {ECO:0000269|PubMed:28534480}.
CC -!- DOMAIN: The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding
CC active site favors the use of Mn(2+) ions to achieve optimal incoming
CC nucleotide stabilization, especially required during primer synthesis
CC (PubMed:30889508). Glu-116 is required to stabilize the incoming
CC nucleotide at the 3'-site (PubMed:30889508).
CC {ECO:0000269|PubMed:30889508}.
CC -!- DISEASE: Myopia 22, autosomal dominant (MYP22) [MIM:615420]: A
CC refractive error of the eye, in which parallel rays from a distant
CC object come to focus in front of the retina, vision being better for
CC near objects than for far. {ECO:0000269|PubMed:23579484,
CC ECO:0000269|PubMed:25262353}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the eukaryotic-type primase small subunit
CC family. {ECO:0000305}.
CC -!- CAUTION: According to a report, the association between the variant
CC Asp-89 and high myopia MYP22 is unclear as this variant is found in
CC control populations (PubMed:25680975). The paper also questions the
CC relevance of functional study on this variant (PubMed:25680975).
CC Authors of the functional characterization study replied that their
CC analysis clearly shows that Asp-89 variant affects the DNA polymerase
CC and primase activities, regardless of its association with high myopia
CC MYP22 (PubMed:25680976). Additional studies are therefore required to
CC confirm the link between this variant and high myopia MYP22.
CC {ECO:0000269|PubMed:25680975, ECO:0000269|PubMed:25680976,
CC ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK057729; BAB71553.1; -; mRNA.
DR EMBL; BX647575; CAI46079.1; -; mRNA.
DR EMBL; AC079257; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF459591; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX04667.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04669.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04670.1; -; Genomic_DNA.
DR EMBL; BC064600; AAH64600.1; -; mRNA.
DR CCDS; CCDS3837.1; -. [Q96LW4-1]
DR CCDS; CCDS75211.1; -. [Q96LW4-2]
DR RefSeq; NP_001287696.1; NM_001300767.1.
DR RefSeq; NP_001287697.1; NM_001300768.1. [Q96LW4-2]
DR RefSeq; NP_001332824.1; NM_001345895.1. [Q96LW4-1]
DR RefSeq; NP_001332825.1; NM_001345896.1. [Q96LW4-2]
DR RefSeq; NP_689896.1; NM_152683.3. [Q96LW4-1]
DR PDB; 5L2X; X-ray; 2.20 A; A/B=1-353.
DR PDB; 5N85; X-ray; 2.00 A; B=514-528.
DR PDB; 5N8A; X-ray; 1.28 A; X=480-560.
DR PDB; 7JK1; X-ray; 2.62 A; A/B=1-354.
DR PDB; 7JKL; X-ray; 2.38 A; A/B=1-354.
DR PDB; 7JKP; X-ray; 2.59 A; A/B=1-354.
DR PDB; 7JL8; X-ray; 2.10 A; A/B=1-354.
DR PDB; 7JLG; X-ray; 2.07 A; A/B=1-354.
DR PDBsum; 5L2X; -.
DR PDBsum; 5N85; -.
DR PDBsum; 5N8A; -.
DR PDBsum; 7JK1; -.
DR PDBsum; 7JKL; -.
DR PDBsum; 7JKP; -.
DR PDBsum; 7JL8; -.
DR PDBsum; 7JLG; -.
DR AlphaFoldDB; Q96LW4; -.
DR SMR; Q96LW4; -.
DR BioGRID; 128410; 24.
DR IntAct; Q96LW4; 18.
DR MINT; Q96LW4; -.
DR STRING; 9606.ENSP00000313816; -.
DR iPTMnet; Q96LW4; -.
DR PhosphoSitePlus; Q96LW4; -.
DR BioMuta; PRIMPOL; -.
DR DMDM; 296434425; -.
DR EPD; Q96LW4; -.
DR jPOST; Q96LW4; -.
DR MassIVE; Q96LW4; -.
DR PaxDb; Q96LW4; -.
DR PeptideAtlas; Q96LW4; -.
DR PRIDE; Q96LW4; -.
DR ProteomicsDB; 14139; -.
DR ProteomicsDB; 77258; -. [Q96LW4-1]
DR Antibodypedia; 66503; 35 antibodies from 10 providers.
DR DNASU; 201973; -.
DR Ensembl; ENST00000314970.11; ENSP00000313816.6; ENSG00000164306.11. [Q96LW4-1]
DR Ensembl; ENST00000503752.5; ENSP00000420860.1; ENSG00000164306.11. [Q96LW4-1]
DR Ensembl; ENST00000512834.5; ENSP00000425316.1; ENSG00000164306.11. [Q96LW4-2]
DR GeneID; 201973; -.
DR KEGG; hsa:201973; -.
DR MANE-Select; ENST00000314970.11; ENSP00000313816.6; NM_152683.4; NP_689896.1.
DR UCSC; uc003iwj.3; human.
DR UCSC; uc003iwk.3; human. [Q96LW4-1]
DR CTD; 201973; -.
DR DisGeNET; 201973; -.
DR GeneCards; PRIMPOL; -.
DR HGNC; HGNC:26575; PRIMPOL.
DR HPA; ENSG00000164306; Low tissue specificity.
DR MalaCards; PRIMPOL; -.
DR MIM; 615420; phenotype.
DR MIM; 615421; gene.
DR neXtProt; NX_Q96LW4; -.
DR OpenTargets; ENSG00000164306; -.
DR PharmGKB; PA145008751; -.
DR VEuPathDB; HostDB:ENSG00000164306; -.
DR eggNOG; ENOG502QS1Q; Eukaryota.
DR GeneTree; ENSGT00390000003901; -.
DR InParanoid; Q96LW4; -.
DR OMA; ADWWMDA; -.
DR OrthoDB; 1373896at2759; -.
DR PhylomeDB; Q96LW4; -.
DR TreeFam; TF328961; -.
DR BRENDA; 2.7.7.102; 2681.
DR PathwayCommons; Q96LW4; -.
DR SignaLink; Q96LW4; -.
DR BioGRID-ORCS; 201973; 9 hits in 1059 CRISPR screens.
DR ChiTaRS; PRIMPOL; human.
DR GenomeRNAi; 201973; -.
DR Pharos; Q96LW4; Tbio.
DR PRO; PR:Q96LW4; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q96LW4; protein.
DR Bgee; ENSG00000164306; Expressed in cerebellar hemisphere and 174 other tissues.
DR ExpressionAtlas; Q96LW4; baseline and differential.
DR Genevisible; Q96LW4; HS.
DR GO; GO:0000428; C:DNA-directed RNA polymerase complex; IEA:UniProtKB-KW.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005657; C:replication fork; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003896; F:DNA primase activity; IDA:UniProtKB.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IDA:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0042276; P:error-prone translesion synthesis; IDA:UniProtKB.
DR GO; GO:0043504; P:mitochondrial DNA repair; ISS:UniProtKB.
DR GO; GO:0006264; P:mitochondrial DNA replication; IMP:UniProtKB.
DR GO; GO:0062176; P:R-loop disassembly; IDA:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; IDA:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR GO; GO:0019985; P:translesion synthesis; IMP:UniProtKB.
DR InterPro; IPR002755; DNA_primase_S.
DR InterPro; IPR044917; PRIMPOL.
DR PANTHER; PTHR31399; PTHR31399; 1.
DR Pfam; PF01896; DNA_primase_S; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Coiled coil;
KW Disease variant; DNA damage; DNA repair; DNA-directed DNA polymerase;
KW DNA-directed RNA polymerase; Manganese; Metal-binding; Mitochondrion;
KW Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transferase; Zinc.
FT CHAIN 1..560
FT /note="DNA-directed primase/polymerase protein"
FT /id="PRO_0000279395"
FT REGION 203..223
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 480..507
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 481..560
FT /note="Interaction with RPA1"
FT /evidence="ECO:0000269|PubMed:24126761"
FT COILED 1..22
FT /evidence="ECO:0000255"
FT MOTIF 419..452
FT /note="Zinc knuckle motif"
FT /evidence="ECO:0000269|PubMed:24240614"
FT MOTIF 513..527
FT /note="RPA1-binding motif 1"
FT /evidence="ECO:0000269|PubMed:28534480"
FT MOTIF 548..556
FT /note="RPA1-binding motif 2"
FT /evidence="ECO:0000269|PubMed:28534480"
FT COMPBIAS 493..507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 76
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:27819052,
FT ECO:0007744|PDB:5L2X"
FT BINDING 114..116
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:27819052,
FT ECO:0007744|PDB:5L2X"
FT BINDING 114
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:24126761,
FT ECO:0000305|PubMed:27819052, ECO:0007744|PDB:5L2X"
FT BINDING 116
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:27819052,
FT ECO:0007744|PDB:5L2X"
FT BINDING 165..169
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:27819052,
FT ECO:0007744|PDB:5L2X"
FT BINDING 288..291
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:27819052,
FT ECO:0007744|PDB:5L2X"
FT BINDING 297
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:27819052,
FT ECO:0007744|PDB:5L2X"
FT BINDING 419
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:24240614"
FT BINDING 426
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:24240614"
FT BINDING 446
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:24240614"
FT BINDING 451
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:24240614"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 366
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_053600"
FT VARIANT 89
FT /note="Y -> D (in MYP22; unknown pathological significance;
FT reduced DNA polymerase and DNA primase activities; reduced
FT DNA-binding; dbSNP:rs200857997)"
FT /evidence="ECO:0000269|PubMed:23579484,
FT ECO:0000269|PubMed:25262353"
FT /id="VAR_070120"
FT VARIANT 168
FT /note="R -> Q (in dbSNP:rs2463447)"
FT /id="VAR_030878"
FT VARIANT 505
FT /note="T -> K (in dbSNP:rs14969)"
FT /id="VAR_030879"
FT MUTAGEN 89
FT /note="Y->F: Does not affect DNA primase activity."
FT /evidence="ECO:0000269|PubMed:25262353"
FT MUTAGEN 89
FT /note="Y->S: Reduced DNA primase activity."
FT /evidence="ECO:0000269|PubMed:25262353"
FT MUTAGEN 114..116
FT /note="DLE->ALA: In AxA; abolished DNA primase and
FT polymerase activities."
FT /evidence="ECO:0000269|PubMed:24207056,
FT ECO:0000269|PubMed:24267451, ECO:0000269|PubMed:24682820,
FT ECO:0000269|PubMed:26626482, ECO:0000269|PubMed:29608762,
FT ECO:0000269|PubMed:30478192, ECO:0000269|PubMed:30889508"
FT MUTAGEN 114
FT /note="D->A: Abolishes DNA primase and polymerase
FT activities."
FT /evidence="ECO:0000269|PubMed:24126761"
FT MUTAGEN 169
FT /note="H->N: Abolishes DNA primase and polymerase
FT activities."
FT /evidence="ECO:0000269|PubMed:24126761"
FT MUTAGEN 280
FT /note="D->A: Abolished Mn(2+) DNA primase activity."
FT /evidence="ECO:0000269|PubMed:30889508"
FT MUTAGEN 419
FT /note="C->A: Abolished zinc-binding, leading to altered
FT translesion synthesis; when associated with A-426."
FT /evidence="ECO:0000269|PubMed:24682820,
FT ECO:0000269|PubMed:26626482, ECO:0000269|PubMed:30478192"
FT MUTAGEN 419
FT /note="C->G: In mutant CH; abolished DNA primase activity
FT and impaired ability to restart stalled forks; when
FT associated with Y-426."
FT /evidence="ECO:0000269|PubMed:24240614"
FT MUTAGEN 426
FT /note="H->A: Abolished zinc-binding, leading to altered
FT translesion synthesis; when associated with A-419."
FT /evidence="ECO:0000269|PubMed:24682820,
FT ECO:0000269|PubMed:26626482, ECO:0000269|PubMed:30478192"
FT MUTAGEN 426
FT /note="H->D: Abolishes DNA primase activity, while it
FT increases DNA polymerase activity."
FT /evidence="ECO:0000269|PubMed:24126761,
FT ECO:0000269|PubMed:24240614"
FT MUTAGEN 426
FT /note="H->Y: In mutant CH; abolished DNA primase activity
FT and impaired ability to restart stalled forks; when
FT associated with G-419."
FT /evidence="ECO:0000269|PubMed:24126761,
FT ECO:0000269|PubMed:24240614"
FT MUTAGEN 519..522
FT /note="DAYF->RAYA: Abolished interaction with RPA1,
FT impairing recruitment to chromatin and reducing DNA primase
FT activity; when associated with 551-R--A-554."
FT /evidence="ECO:0000269|PubMed:28534480"
FT MUTAGEN 551..554
FT /note="DELI->RELA: Abolished interaction with RPA1,
FT impairing recruitment to chromatin and reducing DNA primase
FT activity; when associated with 519-R--A-522."
FT /evidence="ECO:0000269|PubMed:28534480"
FT CONFLICT 322
FT /note="D -> G (in Ref. 2; CAI46079)"
FT /evidence="ECO:0000305"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 48..57
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 83..90
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 112..118
FT /evidence="ECO:0007829|PDB:7JLG"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 127..146
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 155..159
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 163..172
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 182..192
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 194..199
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 275..279
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:7JL8"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:7JKL"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 322..330
FT /evidence="ECO:0007829|PDB:7JLG"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:7JLG"
FT HELIX 519..521
FT /evidence="ECO:0007829|PDB:5N85"
FT HELIX 551..554
FT /evidence="ECO:0007829|PDB:5N8A"
SQ SEQUENCE 560 AA; 64412 MW; 2B58D2B57F51DD4E CRC64;
MNRKWEAKLK QIEERASHYE RKPLSSVYRP RLSKPEEPPS IWRLFHRQAQ AFNFVKSCKE
DVHVFALECK VGDGQRIYLV TTYAEFWFYY KSRKNLLHCY EVIPENAVCK LYFDLEFNKP
ANPGADGKKM VALLIEYVCK ALQELYGVNC SAEDVLNLDS STDEKFSRHL IFQLHDVAFK
DNIHVGNFLR KILQPALDLL GSEDDDSAPE TTGHGFPHFS EAPARQGFSF NKMFTEKATE
ESWTSNSKKL ERLGSAEQSS PDLSFLVVKN NMGEKHLFVD LGVYTRNRNF RLYKSSKIGK
RVALEVTEDN KFFPIQSKDV SDEYQYFLSS LVSNVRFSDT LRILTCEPSQ NKQKGVGYFN
SIGTSVETIE GFQCSPYPEV DHFVLSLVNK DGIKGGIRRW NYFFPEELLV YDICKYRWCE
NIGRAHKSNN IMILVDLKNE VWYQKCHDPV CKAENFKSDC FPLPAEVCLL FLFKEEEEFT
TDEADETRSN ETQNPHKPSP SRLSTGASAD AVWDNGIDDA YFLEATEDAE LAEAAENSLL
SYNSEVDEIP DELIIEVLQE
