P26019 (DPOLA_DROME) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA polymerase alpha catalytic subunit
EC=2.7.7.7

Gene names

Name:	DNApol-alpha180
Synonyms:	DNApol-alpha, POLA
ORF Names:	CG6349

Organism

Drosophila melanogaster (Fruit fly) [Reference proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Mandibulata › Pancrustacea › Hexapoda › Insecta › Dicondylia › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Eremoneura › Cyclorrhapha › Schizophora › Acalyptratae › Ephydroidea › Drosophilidae › Drosophilinae › Drosophilini › Drosophilina › Drosophiliti › Drosophila › Sophophora › melanogaster group › melanogaster subgroup

Protein attributes

Sequence length	1488 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Polymerase alpha in a complex with DNA primase is a replicative polymerase. In addition to polymerase activity, this DNA polymerase exhibits 3' to 5' exonuclease activity. Ref.3
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). Degradation of single-stranded DNA. It acts progressively in a 3'- to 5'-direction, releasing nucleoside 5'-phosphates.
Cofactor	Binds 1 4Fe-4S cluster By similarity.
Subcellular location	Nucleus Ref.2 Ref.3.
Developmental stage	Expressed both maternally and zygotically. Highest level of zygotic expression seen in second-instar larva, level is reduced at other stages of development. Ref.2
Domain	The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes By similarity.
Miscellaneous	In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.
Sequence similarities	Belongs to the DNA polymerase type-B family. Contains 1 CysA-type zinc finger.
Sequence caution	The sequence AAL48000.1 differs from that shown. Reason: Erroneous initiation. The sequence BAA14340.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence BAA32745.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	DNA damage DNA repair DNA replication
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	4Fe-4S DNA-binding Iron Iron-sulfur Metal-binding Zinc
Molecular function	DNA-directed DNA polymerase Exonuclease Hydrolase Nuclease Nucleotidyltransferase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW DNA replication Inferred from direct assay PubMed 6403945PubMed 6773966. Source: FlyBase neurogenesis Inferred from mutant phenotype PubMed 21549331. Source: FlyBase nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC
Cellular_component	alpha DNA polymerase:primase complex Inferred from direct assay PubMed 1360647PubMed 6403945PubMed 6773966. Source: FlyBase
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-directed DNA polymerase activity Inferred from direct assay PubMed 1360647PubMed 6403945PubMed 6773966. Source: FlyBase exonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleoside binding Inferred from electronic annotation. Source: InterPro nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1488	1488	DNA polymerase alpha catalytic subunit		PRO_0000046432
Regions
	Zinc finger	1296 – 1327	32	CysA-type
	Region	638 – 758	121	Contains conserved residues essential for 3' -> 5' exonuclease activities
	Region	675 – 734	60	DNA-binding region Potential
	Region	1255 – 1380	126	DNA-binding region Potential
	Motif	96 – 103	8	Nuclear localization signal Potential
	Motif	1362 – 1388	27	CysB motif
Sites
	Metal binding	1296	1	Zinc By similarity
	Metal binding	1299	1	Zinc By similarity
	Metal binding	1324	1	Zinc By similarity
	Metal binding	1329	1	Zinc By similarity
	Metal binding	1362	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	1367	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	1385	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	1388	1	Iron-sulfur (4Fe-4S) By similarity
Amino acid modifications
	Modified residue	239	1	Phosphoserine Ref.7
	Modified residue	262	1	Phosphoserine Ref.7
	Modified residue	269	1	Phosphoserine Ref.7
	Modified residue	314	1	Phosphothreonine Ref.7
	Modified residue	317	1	Phosphoserine Ref.7
Experimental info
	Sequence conflict	99	1	S → L in S48157. Ref.2
	Sequence conflict	117	1	E → A in BAA14340. Ref.1
	Sequence conflict	117	1	E → A in BAA32745. Ref.3
	Sequence conflict	137	1	K → KK in S48157. Ref.2
	Sequence conflict	148	1	D → DD in S48157. Ref.2
	Sequence conflict	200	1	I → M in BAA14340. Ref.1
	Sequence conflict	200	1	I → M in BAA32745. Ref.3
	Sequence conflict	210 – 227	18	AEASS…LKPKA → RRPVAITRCWSAFSPRQ in S48157. Ref.2
	Sequence conflict	364	1	F → L in BAA14340. Ref.1
	Sequence conflict	364	1	F → L in BAA32745. Ref.3
	Sequence conflict	376	1	M → I in BAA14340. Ref.1
	Sequence conflict	376	1	M → I in BAA32745. Ref.3
	Sequence conflict	379	1	E → Q in BAA14340. Ref.1
	Sequence conflict	379	1	E → Q in BAA32745. Ref.3
	Sequence conflict	478	1	K → N in BAA14340. Ref.1
	Sequence conflict	478	1	K → N in BAA32745. Ref.3
	Sequence conflict	739	1	E → G in S48157. Ref.2
	Sequence conflict	818 – 819	2	FH → ST in BAA14340. Ref.1
	Sequence conflict	818 – 819	2	FH → ST in BAA32745. Ref.3
	Sequence conflict	819	1	H → Y in AAL48000. Ref.6
	Sequence conflict	842	1	A → R in BAA14340. Ref.1
	Sequence conflict	842	1	A → R in BAA32745. Ref.3
	Sequence conflict	881	1	F → L in BAA14340. Ref.1
	Sequence conflict	881	1	F → L in BAA32745. Ref.3
	Sequence conflict	897 – 898	2	TT → NP in BAA14340. Ref.1
	Sequence conflict	897 – 898	2	TT → NP in BAA32745. Ref.3
	Sequence conflict	992 – 993	2	EI → D in BAA14340. Ref.1
	Sequence conflict	992 – 993	2	EI → D in BAA32745. Ref.3
	Sequence conflict	1155 – 1157	3	EYA → DYR in BAA14340. Ref.1
	Sequence conflict	1155 – 1157	3	EYA → DYR in BAA32745. Ref.3
	Sequence conflict	1178	1	R → L in S48157. Ref.2
	Sequence conflict	1187 – 1189	3	YVI → LCD in BAA14340. Ref.1
	Sequence conflict	1187 – 1189	3	YVI → LCD in BAA32745. Ref.3
	Sequence conflict	1197 – 1205	9	AAMQRAYHL → WPCSEHTIS in S48157. Ref.2
	Sequence conflict	1222 – 1223	2	YY → LL in S48157. Ref.2
	Sequence conflict	1292 – 1310	19	FRFQC…ASAYR → SASSALPVRRSSWRLRTD in S48157. Ref.2
	Sequence conflict	1325 – 1351	27	AKSEC…SMRQY → VSPSAKRHRFSTWQACAILQ LSM in BAA14340. Ref.1
	Sequence conflict	1392	1	S → T in S48157. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P26019 [UniParc]. Last modified March 15, 2004. Version 2. Checksum: 76C65EE2E2D5B065	FASTA	1,488	169,903
	10 20 30 40 50 60 MSESPSEPRA KRQRVDKNGR FAAMERLRQL KGTKNKCKVE DQVDDVYDVV DEREYAKRAQ 70 80 90 100 110 120 EKYGDDWIEE DGTGYAEDLR DFFEDEDEYS DGEEDRKDSK KKKGVAPNSK KRPRENEKPV 130 140 150 160 170 180 TGKASIKNLF SNAVPKKMDV KTSVKDDDIL ADILGEIKEE PAATSEKAEK VIAPAKISVT 190 200 210 220 230 240 SRKFDAAAAK EYMNSFLNNI KVQEQERKKA EASSDNEMLE RILKPKAAVP NTKVAFFSSP 250 260 270 280 290 300 TIKKEPMPEK TPAKKATEDP FSDNEMDFSC LDDDENQFDV EKTQQTEKVS QTKTAAEKTS 310 320 330 340 350 360 QSKVAEKSAP KKETTGSPKE SESEDISRLL NNWESICQMD DDFEKSVLTT EQDSTISSDQ 370 380 390 400 410 420 QLRFWYWEAY EDPVKMPGEV FLFGRTADGK SVCLRVQNIN RVLYLLPRQF LLDPISKEPT 430 440 450 460 470 480 KQKVTVADIY KEFDSEVANQ LKLEFFRSRK VTKSFAHHAI GIEVPQSCDY LEVHYDGKKP 490 500 510 520 530 540 LPNLSADKKY NSIAHIFGAT TNALERFLLD RKIKGPCWLQ VTGFKVSPTP MSWCNTEVTL 550 560 570 580 590 600 TEPKNVELVQ DKGKPAPPPP LTLLSLNVRT SMNPKTSRNE ICMISMLTHN RFHIDRPAPQ 610 620 630 640 650 660 PAFNRHMCAL TRPAVVSWPL DLNFEMAKYK STTVHKHDSE RALLSWFLAQ YQKIDADLIV 670 680 690 700 710 720 TFDSMDCQLN VITDQIVALK IPQWSRMGRL RLSQSFGKRL LEHFVGRMVC DVKRSAEECI 730 740 750 760 770 780 RARSYDLQTL CKQVLKLKES ERMEVNADDL LEMYEKGESI TKLISLTMQD NSYLLRLMCE 790 800 810 820 830 840 LNIMPLALQI TNICGNTMTR TLQGGRSERN EFLLLHAFHE KNYIVPDKKP VSKRSGAGDT 850 860 870 880 890 900 DATLSGADAT MQTKKKAAYA GGLVLEPMRG LYEKYVLLMD FNSLYPSIIQ EYNICFTTVQ 910 920 930 940 950 960 QPVDADELPT LPDSKTEPGI LPLQLKRLVE SRKEVKKLMA APDLSPELQM QYHIRQMALK 970 980 990 1000 1010 1020 LTANSMYGCL GFAHSRFFAQ HLAALVTHKG REILTNTQQL VQKMNYDVVY GDTDSLMINT 1030 1040 1050 1060 1070 1080 NITDYDQVYK IGHNIKQSVN KLYKQLELDI DGVFGCLLLL KKKKYAAIKL SKDSKGNLRR 1090 1100 1110 1120 1130 1140 EQEHKGLDIV RRDWSQLAVM VGKAVLDEVL SEKPLEEKLD AVHAQLEKIK TQIAEGVVPL 1150 1160 1170 1180 1190 1200 PLFVITKQLT RTPQEYANSA SLPHVQVALR MNRERNRRYK KGDMVDYVIC LDGTTNAAMQ 1210 1220 1230 1240 1250 1260 RAYHLDELKT SEDKKLQLDT NYYLGHQIHP VVTRMVEVLE GTDASRIAEC LGMDPTKFRQ 1270 1280 1290 1300 1310 1320 NAQRTQRENT EQSEGESLLK TTLQLYRLCE PFRFQCVTCK TEQLMASAYR PGPSNSHIAV 1330 1340 1350 1360 1370 1380 LQQCAKSECQ TAPIQYLASV RNQLQLSMRQ YVQRFYKNWL VCDHPDCNFN TRTHSLRKKS 1390 1400 1410 1420 1430 1440 HRPLCQKCRS GSLLRQYTER DLYNQLCYLR FMFDLGKQTL QQKPTLTPEL EQAYQLLYET 1450 1460 1470 1480 VDQQLQSSSY VIISLSKLFA RSLAQMSLQP SVAQPQIEAI PSALADVV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and expression during development of Drosophila melanogaster gene for DNA polymerase alpha." Hirose F., Yamaguchi M., Nishida Y., Masutani M., Miyazawa H., Hanaoka F., Matsukage A. Nucleic Acids Res. 19:4991-4998(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 131-136; 181-188 AND 238-251. Strain: Oregon-R.
[2]	"Molecular characterisation of the gene for the 180 kDa subunit of the DNA polymerase-primase of Drosophila melanogaster." Melov S., Vaughan H., Cotterill S. J. Cell Sci. 102:847-856(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE.
[3]	"Specification of regions of DNA replication initiation during embryogenesis in the 65-kilobase DNApolalpha-dE2F locus of Drosophila melanogaster." Sasaki T., Sawado T., Yamaguchi M., Shinomiya T. Mol. Cell. Biol. 19:547-555(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION. Strain: Oregon-R.
[4]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[5]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract] Cited for: GENOME REANNOTATION. Strain: Berkeley.
[6]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 710-1488. Strain: Berkeley. Tissue: Ovary.
[7]	"Phosphoproteome analysis of Drosophila melanogaster embryos." Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P. J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239; SER-262; SER-269; THR-314 AND SER-317, MASS SPECTROMETRY. Tissue: Embryo.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D90310 Genomic DNA. Translation: BAA14340.1. Sequence problems. S48157 mRNA. No translation available. AB011813 Genomic DNA. Translation: BAA32745.1. Sequence problems. AE014297 Genomic DNA. Translation: AAF55908.2. AY070529 mRNA. Translation: AAL48000.1. Different initiation.
PIR	S28079.
RefSeq	NP_536736.2. NM_080488.3.
UniGene	Dm.1592.
3D structure databases
ProteinModelPortal	P26019.
SMR	P26019. Positions 496-1245, 1323-1429.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-23937N.
IntAct	P26019. 1 interaction.
MINT	MINT-206832.
Proteomic databases
PaxDb	P26019.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblMetazoa	FBtr0084115; FBpp0083514; FBgn0259113.
GeneID	42553.
KEGG	dme:Dmel_CG6349.
Organism-specific databases
CTD	42553.
FlyBase	FBgn0259113. DNApol-alpha180.
Phylogenomic databases
eggNOG	COG0417.
GeneTree	ENSGT00550000074891.
KO	K02320.
OMA	GSGTDME.
OrthoDB	EOG4MPG50.
PhylomeDB	P26019.
Gene expression databases
Bgee	P26019.
GermOnline	CG6349. Drosophila melanogaster.
Family and domain databases
Gene3D	3.90.1600.10. 2 hits.
InterPro	IPR006172. DNA-dir_DNA_pol_B. IPR017964. DNA-dir_DNA_pol_B_CS. IPR006133. DNA-dir_DNA_pol_B_exonuc. IPR006134. DNA-dir_DNA_pol_B_multi_dom. IPR004578. DNA-dir_DNA_pol_B_pol2. IPR024647. DNA_pol_a_cat_su_N. IPR023211. DNA_pol_palm_dom. IPR012337. RNaseH-like_dom. IPR015088. Znf_DNA-dir_DNA_pol_B_alpha. [Graphical view]
Pfam	PF12254. DNA_pol_alpha_N. 1 hit. PF00136. DNA_pol_B. 1 hit. PF03104. DNA_pol_B_exo1. 1 hit. PF08996. zf-DNA_Pol. 1 hit. [Graphical view]
PRINTS	PR00106. DNAPOLB.
SMART	SM00486. POLBc. 1 hit. [Graphical view]
SUPFAM	SSF53098. RNaseH_fold. 1 hit.
TIGRFAMs	TIGR00592. pol2. 1 hit.
PROSITE	PS00116. DNA_POLYMERASE_B. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL6039.
GenomeRNAi	42553.
NextBio	829396.

Entry information

Entry name

DPOLA_DROME

Accession

Primary (citable) accession number: P26019
Secondary accession number(s): O77034, Q8T992, Q9VD90

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1992
Last sequence update:	March 15, 2004
Last modified:	May 1, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Drosophila annotation project