Search Results

Overview

Uniprot IDP24928
Protein NameDNA-directed RNA polymerase II subunit RPB1
Gene NamePOLR2A
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1866 KYSPTSPKYSPTSPK
1873 KYSPTSPKYSPTSPT

Function

Catalytic core component of RNA polymerase II (Pol II), a DNA-dependent RNA polymerase which synthesizes mRNA precursors and many functional non-coding RNAs using the four ribonucleoside triphosphates as substrates (By similarity) (PubMed:23748380, PubMed:27193682, PubMed:30190596, PubMed:9852112). Pol II-mediated transcription cycle proceeds through transcription initiation, transcription elongation and transcription termination stages. During transcription initiation, Pol II pre-initiation complex (PIC) is recruited to DNA promoters, with focused-type promoters containing either the initiator (Inr) element, or the TATA-box found in cell-type specific genes and dispersed-type promoters that often contain hypomethylated CpG islands usually found in housekeeping genes. Once the polymerase has escaped from the promoter it enters the elongation phase during which RNA is actively polymerized, based on complementarity with the template DNA strand. Transcription termination involves the release of the RNA transcript and polymerase from the DNA (By similarity) (PubMed:23748380, PubMed:27193682, PubMed:28108474, PubMed:30190596, PubMed:9852112). Forms Pol II active center together with the second largest subunit POLR2B/RPB2. Appends one nucleotide at a time to the 3' end of the nascent RNA, with POLR2A/RPB1 most likely contributing a Mg(2+)-coordinating DxDGD motif, and POLR2B/RPB2 participating in the coordination of a second Mg(2+) ion and providing lysine residues believed to facilitate Watson-Crick base pairing between the incoming nucleotide and template base. Typically, Mg(2+) ions direct a 5' nucleoside triphosphate to form a phosphodiester bond with the 3' hydroxyl of the preceding nucleotide of the nascent RNA, with the elimination of pyrophosphate. The reversible pyrophosphorolysis can occur at high pyrophosphate concentrations (By similarity) (PubMed:30190596, PubMed:8381534, PubMed:9852112). Can proofread the nascent RNA transcript by means of a 3' -> 5' exonuclease activity. If a ribonucleotide is mis-incorporated, backtracks along the template DNA and cleaves the phosphodiester bond releasing the mis-incorporated 5'-ribonucleotide (By similarity) (PubMed:8381534). Through its unique C-terminal domain (CTD, 52 heptapeptide tandem repeats) serves as a platform for assembly of factors that regulate transcription initiation, elongation and termination. CTD phosphorylation on Ser-5 mediates Pol II promoter escape, whereas phosphorylation on Ser-2 is required for Pol II pause release during transcription elongation and further pre-mRNA processing. Additionally, the regulation of gene expression levels depends on the balance between methylation and acetylation levels of the CTD-lysines. Initiation or early elongation steps of transcription of growth-factor-induced immediate early genes are regulated by the acetylation status of the CTD. Methylation and dimethylation have a repressive effect on target genes expression. Cooperates with mRNA splicing machinery in co-transcriptional 5'-end capping and co-transcriptional splicing of pre-mRNA (By similarity) (PubMed:24207025, PubMed:26124092)

Protein Sequence

10 MHGGGPPSGD 20 SACPLRTIKR 30 VQFGVLSPDE 40 LKRMSVTEGG 50 IKYPETTEGG 60 RPKLGGLMDP 70 RQGVIERTGR 80 CQTCAGNMTE 90 CPGHFGHIEL 100 AKPVFHVGFL 110 VKTMKVLRCV 120 CFFCSKLLVD 130 SNNPKIKDIL 140 AKSKGQPKKR 150 LTHVYDLCKG 160 KNICEGGEEM 170 DNKFGVEQPE 180 GDEDLTKEKG 190 HGGCGRYQPR 200 IRRSGLELYA 210 EWKHVNEDSQ 220 EKKILLSPER 230 VHEIFKRISD 240 EECFVLGMEP 250 RYARPEWMIV 260 TVLPVPPLSV 270 RPAVVMQGSA 280 RNQDDLTHKL 290 ADIVKINNQL 300 RRNEQNGAAA 310 HVIAEDVKLL 320 QFHVATMVDN 330 ELPGLPRAMQ 340 KSGRPLKSLK 350 QRLKGKEGRV 360 RGNLMGKRVD 370 FSARTVITPD 380 PNLSIDQVGV 390 PRSIAANMTF 400 AEIVTPFNID 410 RLQELVRRGN 420 SQYPGAKYII 430 RDNGDRIDLR 440 FHPKPSDLHL 450 QTGYKVERHM 460 CDGDIVIFNR 470 QPTLHKMSMM 480 GHRVRILPWS 490 TFRLNLSVTT 500 PYNADFDGDE 510 MNLHLPQSLE 520 TRAEIQELAM 530 VPRMIVTPQS 540 NRPVMGIVQD 550 TLTAVRKFTK 560 RDVFLERGEV 570 MNLLMFLSTW 580 DGKVPQPAIL 590 KPRPLWTGKQ 600 IFSLIIPGHI 610 NCIRTHSTHP 620 DDEDSGPYKH 630 ISPGDTKVVV 640 ENGELIMGIL 650 CKKSLGTSAG 660 SLVHISYLEM 670 GHDITRLFYS 680 NIQTVINNWL 690 LIEGHTIGIG 700 DSIADSKTYQ 710 DIQNTIKKAK 720 QDVIEVIEKA 730 HNNELEPTPG 740 NTLRQTFENQ 750 VNRILNDARD 760 KTGSSAQKSL 770 SEYNNFKSMV 780 VSGAKGSKIN 790 ISQVIAVVGQ 800 QNVEGKRIPF 810 GFKHRTLPHF 820 IKDDYGPESR 830 GFVENSYLAG 840 LTPTEFFFHA 850 MGGREGLIDT 860 AVKTAETGYI 870 QRRLIKSMES 880 VMVKYDATVR 890 NSINQVVQLR 900 YGEDGLAGES 910 VEFQNLATLK 920 PSNKAFEKKF 930 RFDYTNERAL 940 RRTLQEDLVK 950 DVLSNAHIQN 960 ELEREFERMR 970 EDREVLRVIF 980 PTGDSKVVLP 990 CNLLRMIWNA 1000 QKIFHINPRL 1010 PSDLHPIKVV 1020 EGVKELSKKL 1030 VIVNGDDPLS 1040 RQAQENATLL 1050 FNIHLRSTLC 1060 SRRMAEEFRL 1070 SGEAFDWLLG 1080 EIESKFNQAI 1090 AHPGEMVGAL 1100 AAQSLGEPAT 1110 QMTLNTFHYA 1120 GVSAKNVTLG 1130 VPRLKELINI 1140 SKKPKTPSLT 1150 VFLLGQSARD 1160 AERAKDILCR 1170 LEHTTLRKVT 1180 ANTAIYYDPN 1190 PQSTVVAEDQ 1200 EWVNVYYEMP 1210 DFDVARISPW 1220 LLRVELDRKH 1230 MTDRKLTMEQ 1240 IAEKINAGFG 1250 DDLNCIFNDD 1260 NAEKLVLRIR 1270 IMNSDENKMQ 1280 EEEEVVDKMD 1290 DDVFLRCIES 1300 NMLTDMTLQG 1310 IEQISKVYMH 1320 LPQTDNKKKI 1330 IITEDGEFKA 1340 LQEWILETDG 1350 VSLMRVLSEK 1360 DVDPVRTTSN 1370 DIVEIFTVLG 1380 IEAVRKALER 1390 ELYHVISFDG 1400 SYVNYRHLAL 1410 LCDTMTCRGH 1420 LMAITRHGVN 1430 RQDTGPLMKC 1440 SFEETVDVLM 1450 EAAAHGESDP 1460 MKGVSENIML 1470 GQLAPAGTGC 1480 FDLLLDAEKC 1490 KYGMEIPTNI 1500 PGLGAAGPTG 1510 MFFGSAPSPM 1520 GGISPAMTPW 1530 NQGATPAYGA 1540 WSPSVGSGMT 1550 PGAAGFSPSA 1560 ASDASGFSPG 1570 YSPAWSPTPG 1580 SPGSPGPSSP 1590 YIPSPGGAMS 1600 PSYSPTSPAY 1610 EPRSPGGYTP 1620 QSPSYSPTSP 1630 SYSPTSPSYS 1640 PTSPNYSPTS 1650 PSYSPTSPSY 1660 SPTSPSYSPT 1670 SPSYSPTSPS 1680 YSPTSPSYSP 1690 TSPSYSPTSP 1700 SYSPTSPSYS 1710 PTSPSYSPTS 1720 PSYSPTSPSY 1730 SPTSPSYSPT 1740 SPSYSPTSPS 1750 YSPTSPNYSP 1760 TSPNYTPTSP 1770 SYSPTSPSYS 1780 PTSPNYTPTS 1790 PNYSPTSPSY 1800 SPTSPSYSPT 1810 SPSYSPSSPR 1820 YTPQSPTYTP 1830 SSPSYSPSSP 1840 SYSPTSPKYT 1850 PTSPSYSPSS 1860 PEYTPTSPKY 1870 SPTSPKYSPT 1880 SPKYSPTSPT 1890 YSPTTPKYSP 1900 TSPTYSPTSP 1910 VYTPTSPKYS 1920 PTSPTYSPTS 1930 PKYSPTSPTY 1940 SPTSPKGSTY 1950 SPTSPGYSPT 1960 SPTYSLTSPA 1970 ISPDDSDEEN

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005694 chromosome
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005665 RNA polymerase II, core complex
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0003899 DNA-directed RNA polymerase activity
Molecular Function GO:0016787 hydrolase activity
Molecular Function GO:0019900 kinase binding
Molecular Function GO:0000287 magnesium ion binding
Molecular Function GO:0050436 microfibril binding
Molecular Function GO:1990841 promoter-specific chromatin binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0003968 RNA-directed RNA polymerase activity
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006353 DNA-templated transcription termination
Biological Process GO:0042789 mRNA transcription by RNA polymerase II
Biological Process GO:0033120 positive regulation of RNA splicing
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0006369 termination of RNA polymerase II transcription
Biological Process GO:0006366 transcription by RNA polymerase II
Biological Process GO:0006368 transcription elongation by RNA polymerase II
Biological Process GO:0006367 transcription initiation at RNA polymerase II promoter

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.