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Overview

Uniprot IDP09884
Protein NameDNA polymerase alpha catalytic subunit
Gene NamePOLA1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
125 KDKRNVKKLAVTKPN
130 VKKLAVTKPNNIKSM
149 AGKKTADKAVDLSKD
206 ATAVPSGKIASPVSR
214 IASPVSRKEPPLTPV
224 PLTPVPLKRAEFAGD

Function

Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses (PubMed:27019227)

Protein Sequence

10 MAPVHGDDSL 20 SDSGSFVSSR 30 ARREKKSKKG 40 RQEALERLKK 50 AKAGEKYKYE 60 VEDFTGVYEE 70 VDEEQYSKLV 80 QARQDDDWIV 90 DDDGIGYVED 100 GREIFDDDLE 110 DDALDADEKG 120 KDGKARNKDK 130 RNVKKLAVTK 140 PNNIKSMFIA 150 CAGKKTADKA 160 VDLSKDGLLG 170 DILQDLNTET 180 PQITPPPVMI 190 LKKKRSIGAS 200 PNPFSVHTAT 210 AVPSGKIASP 220 VSRKEPPLTP 230 VPLKRAEFAG 240 DDVQVESTEE 250 EQESGAMEFE 260 DGDFDEPMEV 270 EEVDLEPMAA 280 KAWDKESEPA 290 EEVKQEADSG 300 KGTVSYLGSF 310 LPDVSCWDID 320 QEGDSSFSVQ 330 EVQVDSSHLP 340 LVKGADEEQV 350 FHFYWLDAYE 360 DQYNQPGVVF 370 LFGKVWIESA 380 ETHVSCCVMV 390 KNIERTLYFL 400 PREMKIDLNT 410 GKETGTPISM 420 KDVYEEFDEK 430 IATKYKIMKF 440 KSKPVEKNYA 450 FEIPDVPEKS 460 EYLEVKYSAE 470 MPQLPQDLKG 480 ETFSHVFGTN 490 TSSLELFLMN 500 RKIKGPCWLE 510 VKSPQLLNQP 520 VSWCKVEAMA 530 LKPDLVNVIK 540 DVSPPPLVVM 550 AFSMKTMQNA 560 KNHQNEIIAM 570 AALVHHSFAL 580 DKAAPKPPFQ 590 SHFCVVSKPK 600 DCIFPYAFKE 610 VIEKKNVKVE 620 VAATERTLLG 630 FFLAKVHKID 640 PDIIVGHNIY 650 GFELEVLLQR 660 INVCKAPHWS 670 KIGRLKRSNM 680 PKLGGRSGFG 690 ERNATCGRMI 700 CDVEISAKEL 710 IRCKSYHLSE 720 LVQQILKTER 730 VVIPMENIQN 740 MYSESSQLLY 750 LLEHTWKDAK 760 FILQIMCELN 770 VLPLALQITN 780 IAGNIMSRTL 790 MGGRSERNEF 800 LLLHAFYENN 810 YIVPDKQIFR 820 KPQQKLGDED 830 EEIDGDTNKY 840 KKGRKKAAYA 850 GGLVLDPKVG 860 FYDKFILLLD 870 FNSLYPSIIQ 880 EFNICFTTVQ 890 RVASEAQKVT 900 EDGEQEQIPE 910 LPDPSLEMGI 920 LPREIRKLVE 930 RRKQVKQLMK 940 QQDLNPDLIL 950 QYDIRQKALK 960 LTANSMYGCL 970 GFSYSRFYAK 980 PLAALVTYKG 990 REILMHTKEM 1000 VQKMNLEVIY 1010 GDTDSIMINT 1020 NSTNLEEVFK 1030 LGNKVKSEVN 1040 KLYKLLEIDI 1050 DGVFKSLLLL 1060 KKKKYAALVV 1070 EPTSDGNYVT 1080 KQELKGLDIV 1090 RRDWCDLAKD 1100 TGNFVIGQIL 1110 SDQSRDTIVE 1120 NIQKRLIEIG 1130 ENVLNGSVPV 1140 SQFEINKALT 1150 KDPQDYPDKK 1160 SLPHVHVALW 1170 INSQGGRKVK 1180 AGDTVSYVIC 1190 QDGSNLTASQ 1200 RAYAPEQLQK 1210 QDNLTIDTQY 1220 YLAQQIHPVV 1230 ARICEPIDGI 1240 DAVLIATWLG 1250 LDPTQFRVHH 1260 YHKDEENDAL 1270 LGGPAQLTDE 1280 EKYRDCERFK 1290 CPCPTCGTEN 1300 IYDNVFDGSG 1310 TDMEPSLYRC 1320 SNIDCKASPL 1330 TFTVQLSNKL 1340 IMDIRRFIKK 1350 YYDGWLICEE 1360 PTCRNRTRHL 1370 PLQFSRTGPL 1380 CPACMKATLQ 1390 PEYSDKSLYT 1400 QLCFYRYIFD 1410 AECALEKLTT 1420 DHEKDKLKKQ 1430 FFTPKVLQDY 1440 RKLKNTAEQF 1450 LSRSGYSEVN 1460 LSKLFAGCAV KS

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005658 alpha DNA polymerase:primase complex
Molecular Function GO:0003688 DNA replication origin binding
Molecular Function GO:0003887 DNA-directed DNA polymerase activity
Molecular Function GO:0000166 nucleotide binding
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0003697 single-stranded DNA binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006281 DNA repair
Biological Process GO:0006260 DNA replication
Biological Process GO:0006270 DNA replication initiation
Biological Process GO:0006269 DNA replication, synthesis of primer
Biological Process GO:0006271 DNA strand elongation involved in DNA replication
Biological Process GO:0000731 DNA synthesis involved in DNA repair
Biological Process GO:0006303 double-strand break repair via nonhomologous end joining
Biological Process GO:0006273 lagging strand elongation
Biological Process GO:0006272 leading strand elongation
Biological Process GO:1902975 mitotic DNA replication initiation
Biological Process GO:0032479 regulation of type I interferon production
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005635 nuclear envelope
Cellular Component GO:0016363 nuclear matrix
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0003677 DNA binding

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.