Search Results

Overview

Uniprot IDQ09472
Protein NameHistone acetyltransferase p300
Gene NameEP300
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
14 EPGPPSAKRPKLSSP
17 PPSAKRPKLSSPALS
1800 AKHCQENKCPVPFCL
1810 VPFCLNIKQKLRQQQ
1812 FCLNIKQKLRQQQLQ
291 LSPFAMDKKAVPGGG
601 TPDPAALKDRRMENL
79 QDAASKHKQLSELLR

Function

Functions as a histone acetyltransferase and regulates transcription via chromatin remodeling (PubMed:23415232, PubMed:23934153, PubMed:40240600, PubMed:8945521). Acetylates all four core histones in nucleosomes (PubMed:23415232, PubMed:23934153, PubMed:8945521). Histone acetylation gives an epigenetic tag for transcriptional activation (PubMed:23415232, PubMed:23934153, PubMed:8945521). Mediates acetylation of histone H3 at 'Lys-122' (H3K122ac), a modification that localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability (PubMed:23415232). Mediates acetylation of histone H3 at 'Lys-18' and 'Lys-27' (H3K18ac and H3K27ac, respectively) (PubMed:21131905, PubMed:23911289). Also able to acetylate histone lysine residues that are already monomethylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation (PubMed:37731000). Catalyzes formation of histone H4 acetyl-methylated at 'Lys-5' and 'Lys-12' (H4K5acme and H4K12acme, respectively) (PubMed:37731000). In response to DNA damage, catalyzes acetylation of histone H1 at 'Lys-75' (H1K75ac) following histone H1 deamidation by CTPS1, increasing chromatin accessibility to facilitate the recruitment of DNA repair proteins (PubMed:40240600). Also functions as acetyltransferase for non-histone targets, such as ALX1, HDAC1, PRDM16, PRMT1, SIRT2, STAT3, ZNF76 or GLUL (PubMed:12929931, PubMed:15653507, PubMed:16285960, PubMed:16337145, PubMed:16762839, PubMed:18722353, PubMed:18782771, PubMed:26990986). Acetylates 'Lys-131' of ALX1 and acts as its coactivator (PubMed:12929931). Acetylates SIRT2 and is proposed to indirectly increase the transcriptional activity of p53/TP53 through acetylation and subsequent attenuation of SIRT2 deacetylase function (PubMed:18722353). Following DNA damage, forms a stress-responsive p53/TP53 coactivator complex with JMY which mediates p53/TP53 acetylation, thereby increasing p53/TP53-dependent transcription and apoptosis (PubMed:11511361, PubMed:15448695). Promotes chromatin acetylation in heat shock responsive HSP genes during the heat shock response (HSR), thereby stimulating HSR transcription (PubMed:18451878). Acetylates HDAC1 leading to its inactivation and modulation of transcription (PubMed:16762839). Acetylates 'Lys-247' of EGR2 (By similarity). Acts as a TFAP2A-mediated transcriptional coactivator in presence of CITED2 (PubMed:12586840). Plays a role as a coactivator of NEUROD1-dependent transcription of the secretin and p21 genes and controls terminal differentiation of cells in the intestinal epithelium. Promotes cardiac myocyte enlargement (PubMed:14752053). Can also mediate transcriptional repression. Acetylates FOXO1 and enhances its transcriptional activity (PubMed:15890677). Acetylates STAT3 at different sites, promoting both STAT3 dimerization and activation and recruitment to chromatin (PubMed:15653507, PubMed:16285960, PubMed:18782771). Acetylates BCL6 which disrupts its ability to recruit histone deacetylases and hinders its transcriptional repressor activity (PubMed:12402037). Participates in CLOCK or NPAS2-regulated rhythmic gene transcription; exhibits a circadian association with CLOCK or NPAS2, correlating with increase in PER1/2 mRNA and histone H3 acetylation on the PER1/2 promoter (PubMed:14645221). Acetylates MTA1 at 'Lys-626' which is essential for its transcriptional coactivator activity (PubMed:16617102). Acetylates XBP1 isoform 2; acetylation increases protein stability of XBP1 isoform 2 and enhances its transcriptional activity (PubMed:20955178). Acetylates PCNA; acetylation promotes removal of chromatin-bound PCNA and its degradation during nucleotide excision repair (NER) (PubMed:24939902). Acetylates MEF2D (PubMed:21030595). Acetylates and stabilizes ZBTB7B protein by antagonizing ubiquitin conjugation and degradation, this mechanism may be involved in CD4/CD8 lineage differentiation (PubMed:20810990). Acetylates GABPB1, impairing GABPB1 heterotetramerization and activity (By similarity). Acetylates PCK1 and promotes PCK1 anaplerotic activity (PubMed:30193097). Acetylates RXRA and RXRG (PubMed:17761950). Acetylates isoform M2 of PKM (PKM2), promoting its homodimerization and conversion into a protein kinase (PubMed:24120661). Acetylates RPTOR in response to leucine, leading to activation of the mTORC1 complex (PubMed:30197302, PubMed:32561715). Acetylates RICTOR, leading to activation of the mTORC2 complex (PubMed:22084251). Mediates cAMP-gene regulation by binding specifically to phosphorylated CREBBP (PubMed:8917528). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as (2E)-butenoyl-CoA (crotonyl-CoA), butanoyl-CoA (butyryl-CoA), 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA), lactoyl-CoA, propanoyl-CoA (propionyl-CoA) or isonicotinyl-CoA, and is able to mediate protein crotonylation, butyrylation, 2-hydroxyisobutyrylation, lactylation, propionylation or isonicotinylation, respectively (PubMed:17267393, PubMed:25818647, PubMed:29775581, PubMed:31645732, PubMed:34545082). Acts as a histone crotonyltransferase; crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors (PubMed:25818647). Histone crotonyltransferase activity is dependent on the concentration of (2E)-butenoyl-CoA (crotonyl-CoA) substrate and such activity is weak when (2E)-butenoyl-CoA (crotonyl-CoA) concentration is low (PubMed:25818647). Also acts as a histone butyryltransferase; butyrylation marks active promoters (PubMed:17267393). Catalyzes histone lactylation in macrophages by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription (PubMed:31645732). Acts as a protein-lysine 2-hydroxyisobutyryltransferase; regulates glycolysis by mediating 2-hydroxyisobutyrylation of glycolytic enzymes (PubMed:29775581). Functions as a transcriptional coactivator for SMAD4 in the TGF-beta signaling pathway (PubMed:25514493)

Protein Sequence

10 MAENVVEPGP 20 PSAKRPKLSS 30 PALSASASDG 40 TDFGSLFDLE 50 HDLPDELINS 60 TELGLTNGGD 70 INQLQTSLGM 80 VQDAASKHKQ 90 LSELLRSGSS 100 PNLNMGVGGP 110 GQVMASQAQQ 120 SSPGLGLINS 130 MVKSPMTQAG 140 LTSPNMGMGT 150 SGPNQGPTQS 160 TGMMNSPVNQ 170 PAMGMNTGMN 180 AGMNPGMLAA 190 GNGQGIMPNQ 200 VMNGSIGAGR 210 GRQNMQYPNP 220 GMGSAGNLLT 230 EPLQQGSPQM 240 GGQTGLRGPQ 250 PLKMGMMNNP 260 NPYGSPYTQN 270 PGQQIGASGL 280 GLQIQTKTVL 290 SNNLSPFAMD 300 KKAVPGGGMP 310 NMGQQPAPQV 320 QQPGLVTPVA 330 QGMGSGAHTA 340 DPEKRKLIQQ 350 QLVLLLHAHK 360 CQRREQANGE 370 VRQCNLPHCR 380 TMKNVLNHMT 390 HCQSGKSCQV 400 AHCASSRQII 410 SHWKNCTRHD 420 CPVCLPLKNA 430 GDKRNQQPIL 440 TGAPVGLGNP 450 SSLGVGQQSA 460 PNLSTVSQID 470 PSSIERAYAA 480 LGLPYQVNQM 490 PTQPQVQAKN 500 QQNQQPGQSP 510 QGMRPMSNMS 520 ASPMGVNGGV 530 GVQTPSLLSD 540 SMLHSAINSQ 550 NPMMSENASV 560 PSLGPMPTAA 570 QPSTTGIRKQ 580 WHEDITQDLR 590 NHLVHKLVQA 600 IFPTPDPAAL 610 KDRRMENLVA 620 YARKVEGDMY 630 ESANNRAEYY 640 HLLAEKIYKI 650 QKELEEKRRT 660 RLQKQNMLPN 670 AAGMVPVSMN 680 PGPNMGQPQP 690 GMTSNGPLPD 700 PSMIRGSVPN 710 QMMPRITPQS 720 GLNQFGQMSM 730 AQPPIVPRQT 740 PPLQHHGQLA 750 QPGALNPPMG 760 YGPRMQQPSN 770 QGQFLPQTQF 780 PSQGMNVTNI 790 PLAPSSGQAP 800 VSQAQMSSSS 810 CPVNSPIMPP 820 GSQGSHIHCP 830 QLPQPALHQN 840 SPSPVPSRTP 850 TPHHTPPSIG 860 AQQPPATTIP 870 APVPTPPAMP 880 PGPQSQALHP 890 PPRQTPTPPT 900 TQLPQQVQPS 910 LPAAPSADQP 920 QQQPRSQQST 930 AASVPTPTAP 940 LLPPQPATPL 950 SQPAVSIEGQ 960 VSNPPSTSST 970 EVNSQAIAEK 980 QPSQEVKMEA 990 KMEVDQPEPA 1000 DTQPEDISES 1010 KVEDCKMEST 1020 ETEERSTELK 1030 TEIKEEEDQP 1040 STSATQSSPA 1050 PGQSKKKIFK 1060 PEELRQALMP 1070 TLEALYRQDP 1080 ESLPFRQPVD 1090 PQLLGIPDYF 1100 DIVKSPMDLS 1110 TIKRKLDTGQ 1120 YQEPWQYVDD 1130 IWLMFNNAWL 1140 YNRKTSRVYK 1150 YCSKLSEVFE 1160 QEIDPVMQSL 1170 GYCCGRKLEF 1180 SPQTLCCYGK 1190 QLCTIPRDAT 1200 YYSYQNRYHF 1210 CEKCFNEIQG 1220 ESVSLGDDPS 1230 QPQTTINKEQ 1240 FSKRKNDTLD 1250 PELFVECTEC 1260 GRKMHQICVL 1270 HHEIIWPAGF 1280 VCDGCLKKSA 1290 RTRKENKFSA 1300 KRLPSTRLGT 1310 FLENRVNDFL 1320 RRQNHPESGE 1330 VTVRVVHASD 1340 KTVEVKPGMK 1350 ARFVDSGEMA 1360 ESFPYRTKAL 1370 FAFEEIDGVD 1380 LCFFGMHVQE 1390 YGSDCPPPNQ 1400 RRVYISYLDS 1410 VHFFRPKCLR 1420 TAVYHEILIG 1430 YLEYVKKLGY 1440 TTGHIWACPP 1450 SEGDDYIFHC 1460 HPPDQKIPKP 1470 KRLQEWYKKM 1480 LDKAVSERIV 1490 HDYKDIFKQA 1500 TEDRLTSAKE 1510 LPYFEGDFWP 1520 NVLEESIKEL 1530 EQEEEERKRE 1540 ENTSNESTDV 1550 TKGDSKNAKK 1560 KNNKKTSKNK 1570 SSLSRGNKKK 1580 PGMPNVSNDL 1590 SQKLYATMEK 1600 HKEVFFVIRL 1610 IAGPAANSLP 1620 PIVDPDPLIP 1630 CDLMDGRDAF 1640 LTLARDKHLE 1650 FSSLRRAQWS 1660 TMCMLVELHT 1670 QSQDRFVYTC 1680 NECKHHVETR 1690 WHCTVCEDYD 1700 LCITCYNTKN 1710 HDHKMEKLGL 1720 GLDDESNNQQ 1730 AAATQSPGDS 1740 RRLSIQRCIQ 1750 SLVHACQCRN 1760 ANCSLPSCQK 1770 MKRVVQHTKG 1780 CKRKTNGGCP 1790 ICKQLIALCC 1800 YHAKHCQENK 1810 CPVPFCLNIK 1820 QKLRQQQLQH 1830 RLQQAQMLRR 1840 RMASMQRTGV 1850 VGQQQGLPSP 1860 TPATPTTPTG 1870 QQPTTPQTPQ 1880 PTSQPQPTPP 1890 NSMPPYLPRT 1900 QAAGPVSQGK 1910 AAGQVTPPTP 1920 PQTAQPPLPG 1930 PPPAAVEMAM 1940 QIQRAAETQR 1950 QMAHVQIFQR 1960 PIQHQMPPMT 1970 PMAPMGMNPP 1980 PMTRGPSGHL 1990 EPGMGPTGMQ 2000 QQPPWSQGGL 2010 PQPQQLQSGM 2020 PRPAMMSVAQ 2030 HGQPLNMAPQ 2040 PGLGQVGISP 2050 LKPGTVSQQA 2060 LQNLLRTLRS 2070 PSSPLQQQQV 2080 LSILHANPQL 2090 LAAFIKQRAA 2100 KYANSNPQPI 2110 PGQPGMPQGQ 2120 PGLQPPTMPG 2130 QQGVHSNPAM 2140 QNMNPMQAGV 2150 QRAGLPQQQP 2160 QQQLQPPMGG 2170 MSPQAQQMNM 2180 NHNTMPSQFR 2190 DILRRQQMMQ 2200 QQQQQGAGPG 2210 IGPGMANHNQ 2220 FQQPQGVGYP 2230 PQQQQRMQHH 2240 MQQMQQGNMG 2250 QIGQLPQALG 2260 AEAGASLQAY 2270 QQRLLQQQMG 2280 SPVQPNPMSP 2290 QQHMLPNQAQ 2300 SPHLQGQQIP 2310 NSLSNQVRSP 2320 QPVPSPRPQS 2330 QPPHSSPSPR 2340 MQPQPSPHHV 2350 SPQTSSPHPG 2360 LVAAQANPME 2370 QGHFASPDQN 2380 SMLSQLASNP 2390 GMANLHGASA 2400 TDLGLSTDNS 2410 DLNSNLSQST LDIH

Gene Ontology

Classification GO ID Description
Molecular Function GO:0044013 histone H2B acetyltransferase activity
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0000123 histone acetyltransferase complex
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032993 protein-DNA complex
Cellular Component GO:0005667 transcription regulator complex
Molecular Function GO:0140033 acetylation-dependent protein binding
Molecular Function GO:0016407 acetyltransferase activity
Molecular Function GO:0016746 acyltransferase activity
Molecular Function GO:0008013 beta-catenin binding
Molecular Function GO:0003682 chromatin binding
Molecular Function GO:0031490 chromatin DNA binding
Molecular Function GO:0003684 damaged DNA binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0140297 DNA-binding transcription factor binding
Molecular Function GO:0004402 histone acetyltransferase activity
Molecular Function GO:0140069 histone butyryltransferase activity
Molecular Function GO:0140068 histone crotonyltransferase activity
Molecular Function GO:0160263 histone H1K75 acetyltransferase activity
Biological Process GO:0002223 stimulatory C-type lectin receptor signaling pathway
Biological Process GO:0036268 swimming
Biological Process GO:0001966 thigmotaxis
Biological Process GO:0045815 transcription initiation-coupled chromatin remodeling
Molecular Function GO:0010484 histone H3 acetyltransferase activity
Molecular Function GO:0140908 histone H3K122 acetyltransferase activity
Molecular Function GO:0043993 histone H3K18 acetyltransferase activity
Molecular Function GO:0044017 histone H3K27 acetyltransferase activity
Molecular Function GO:0010485 histone H4 acetyltransferase activity
Molecular Function GO:0140230 histone isonicotinyltransferase activity
Molecular Function GO:0120301 histone lactyltransferase (CoA-dependent) activity
Molecular Function GO:0004468 L-lysine N-acetyltransferase activity, acting on acetyl phosphate as donor
Molecular Function GO:0051059 NF-kappaB binding
Molecular Function GO:0050681 nuclear androgen receptor binding
Molecular Function GO:0016922 nuclear receptor binding
Molecular Function GO:0002039 p53 binding
Molecular Function GO:0106226 peptide 2-hydroxyisobutyryltransferase activity
Molecular Function GO:0140065 peptide butyryltransferase activity
Molecular Function GO:0097157 pre-mRNA intronic binding
Molecular Function GO:0061920 protein propionyltransferase activity
Molecular Function GO:0061733 protein-lysine-acetyltransferase activity
Molecular Function GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
Molecular Function GO:0097677 STAT family protein binding
Molecular Function GO:0048156 tau protein binding
Molecular Function GO:0003713 transcription coactivator activity
Molecular Function GO:0001223 transcription coactivator binding
Molecular Function GO:0001221 transcription coregulator binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006915 apoptotic process
Biological Process GO:0002209 behavioral defense response
Biological Process GO:0007249 canonical NF-kappaB signal transduction
Biological Process GO:0060070 canonical Wnt signaling pathway
Biological Process GO:0071233 cellular response to L-leucine
Biological Process GO:0031669 cellular response to nutrient levels
Biological Process GO:0034644 cellular response to UV
Biological Process GO:0007623 circadian rhythm
Biological Process GO:0140861 DNA repair-dependent chromatin remodeling
Biological Process GO:0060325 face morphogenesis
Biological Process GO:0045444 fat cell differentiation
Biological Process GO:0043923 host-mediated activation of viral transcription
Biological Process GO:0018393 internal peptidyl-lysine acetylation
Biological Process GO:0006475 internal protein amino acid acetylation
Biological Process GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Biological Process GO:0007611 learning or memory
Biological Process GO:0035264 multicellular organism growth
Biological Process GO:0010507 negative regulation of autophagy
Biological Process GO:1903444 negative regulation of brown fat cell differentiation
Biological Process GO:1902340 negative regulation of chromosome condensation
Biological Process GO:0045721 negative regulation of gluconeogenesis
Biological Process GO:0032460 negative regulation of protein oligomerization
Biological Process GO:0031333 negative regulation of protein-containing complex assembly
Biological Process GO:0000122 negative regulation of transcription by RNA polymerase II
Biological Process GO:0007399 nervous system development
Biological Process GO:0140067 peptidyl-lysine butyrylation
Biological Process GO:0140066 peptidyl-lysine crotonylation
Biological Process GO:0061921 peptidyl-lysine propionylation
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0010976 positive regulation of neuron projection development
Biological Process GO:0042307 positive regulation of protein import into nucleus
Biological Process GO:0046427 positive regulation of receptor signaling pathway via JAK-STAT
Biological Process GO:2000330 positive regulation of T-helper 17 cell lineage commitment
Biological Process GO:1904263 positive regulation of TORC1 signaling
Biological Process GO:1904515 positive regulation of TORC2 signaling
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway
Biological Process GO:0006473 protein acetylation
Biological Process GO:0031648 protein destabilization
Biological Process GO:0050821 protein stabilization
Biological Process GO:0060765 regulation of androgen receptor signaling pathway
Biological Process GO:0010506 regulation of autophagy
Biological Process GO:1900034 regulation of cellular response to heat
Biological Process GO:0006110 regulation of glycolytic process
Biological Process GO:0010821 regulation of mitochondrion organization
Biological Process GO:2000819 regulation of nucleotide-excision repair
Biological Process GO:1901796 regulation of signal transduction by p53 class mediator
Biological Process GO:0090043 regulation of tubulin deacetylation
Biological Process GO:0043627 response to estrogen
Biological Process GO:0001666 response to hypoxia

Reference

[1] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.