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Overview

Uniprot IDP29590
Protein NameProtein PML
Gene NamePML
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
394 SSCITQGKDAAVSKK
400 GKDAAVSKKASPEAA
401 KDAAVSKKASPEAAS
476 SNTTTAQKRKCSQTQ
478 TTTAQKRKCSQTQCP
490 QCPRKVIKMESEEGK

Function

Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs (PubMed:11500381, PubMed:11575918, PubMed:18391071). Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration

Protein Sequence

10 MEPAPARSPR 20 PQQDPARPQE 30 PTMPPPETPS 40 EGRQPSPSPS 50 PTERAPASEE 60 EFQFLRCQQC 70 QAEAKCPKLL 80 PCLHTLCSGC 90 LEASGMQCPI 100 CQAPWPLGAD 110 TPALDNVFFE 120 SLQRRLSVYR 130 QIVDAQAVCT 140 RCKESADFWC 150 FECEQLLCAK 160 CFEAHQWFLK 170 HEARPLAELR 180 NQSVREFLDG 190 TRKTNNIFCS 200 NPNHRTPTLT 210 SIYCRGCSKP 220 LCCSCALLDS 230 SHSELKCDIS 240 AEIQQRQEEL 250 DAMTQALQEQ 260 DSAFGAVHAQ 270 MHAAVGQLGR 280 ARAETEELIR 290 ERVRQVVAHV 300 RAQERELLEA 310 VDARYQRDYE 320 EMASRLGRLD 330 AVLQRIRTGS 340 ALVQRMKCYA 350 SDQEVLDMHG 360 FLRQALCRLR 370 QEEPQSLQAA 380 VRTDGFDEFK 390 VRLQDLSSCI 400 TQGKDAAVSK 410 KASPEAASTP 420 RDPIDVDLPE 430 EAERVKAQVQ 440 ALGLAEAQPM 450 AVVQSVPGAH 460 PVPVYAFSIK 470 GPSYGEDVSN 480 TTTAQKRKCS 490 QTQCPRKVIK 500 MESEEGKEAR 510 LARSSPEQPR 520 PSTSKAVSPP 530 HLDGPPSPRS 540 PVIGSEVFLP 550 NSNHVASGAG 560 EAEERVVVIS 570 SSEDSDAENS 580 SSRELDDSSS 590 ESSDLQLEGP 600 STLRVLDENL 610 ADPQAEDRPL 620 VFFDLKIDNE 630 TQKISQLAAV 640 NRESKFRVVI 650 QPEAFFSIYS 660 KAVSLEVGLQ 670 HFLSFLSSMR 680 RPILACYKLW 690 GPGLPNFFRA 700 LEDINRLWEF 710 QEAISGFLAA 720 LPLIRERVPG 730 ASSFKLKNLA 740 QTYLARNMSE 750 RSAMAAVLAM 760 RDLCRLLEVS 770 PGPQLAQHVY 780 PFSSLQCFAS 790 LQPLVQAAVL 800 PRAEARLLAL 810 HNVSFMELLS 820 AHRRDRQGGL 830 KKYSRYLSLQ 840 TTTLPPAQPA 850 FNLQALGTYF 860 EGLLEGPALA 870 RAEGVSTPLA 880 GRGLAERASQ QS

Gene Ontology

Classification GO ID Description
Biological Process GO:0030155 regulation of cell adhesion
Cellular Component GO:0000781 chromosome, telomeric region
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0031901 early endosome membrane
Cellular Component GO:0005789 endoplasmic reticulum membrane
Cellular Component GO:0016604 nuclear body
Cellular Component GO:0016363 nuclear matrix
Cellular Component GO:0031965 nuclear membrane
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0016605 PML body
Molecular Function GO:0050897 cobalt ion binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0060090 molecular adaptor activity
Molecular Function GO:0046982 protein heterodimerization activity
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0046332 SMAD binding
Molecular Function GO:0032183 SUMO binding
Molecular Function GO:0019789 SUMO transferase activity
Molecular Function GO:0003713 transcription coactivator activity
Molecular Function GO:0031625 ubiquitin protein ligase binding
Molecular Function GO:0061659 ubiquitin-like protein ligase activity
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0006915 apoptotic process
Biological Process GO:0090398 cellular senescence
Biological Process GO:0006338 chromatin remodeling
Biological Process GO:0032922 circadian regulation of gene expression
Biological Process GO:0030330 DNA damage response, signal transduction by p53 class mediator
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0032469 endoplasmic reticulum calcium ion homeostasis
Biological Process GO:0043153 entrainment of circadian clock by photoperiod
Biological Process GO:0045184 establishment of protein localization
Biological Process GO:0010761 fibroblast migration
Biological Process GO:0045087 innate immune response
Biological Process GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
Biological Process GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Biological Process GO:0051457 maintenance of protein location in nucleus
Biological Process GO:0016525 negative regulation of angiogenesis
Biological Process GO:0030308 negative regulation of cell growth
Biological Process GO:0008285 negative regulation of cell population proliferation
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:0032691 negative regulation of interleukin-1 beta production
Biological Process GO:0045930 negative regulation of mitotic cell cycle
Biological Process GO:0032211 negative regulation of telomere maintenance via telomerase
Biological Process GO:0032938 negative regulation of translation in response to oxidative stress
Biological Process GO:2000059 negative regulation of ubiquitin-dependent protein catabolic process
Biological Process GO:0090402 oncogene-induced cell senescence
Biological Process GO:0030578 PML body organization
Biological Process GO:0060058 positive regulation of apoptotic process involved in mammary gland involution
Biological Process GO:0002230 positive regulation of defense response to virus by host
Biological Process GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
Biological Process GO:0048146 positive regulation of fibroblast proliferation
Biological Process GO:1904816 positive regulation of protein localization to chromosome, telomeric region
Biological Process GO:1901798 positive regulation of signal transduction by p53 class mediator
Biological Process GO:0032206 positive regulation of telomere maintenance
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0050821 protein stabilization
Biological Process GO:0016925 protein sumoylation
Biological Process GO:0006605 protein targeting
Biological Process GO:0065003 protein-containing complex assembly
Biological Process GO:0010522 regulation of calcium ion transport into cytosol
Biological Process GO:0051726 regulation of cell cycle
Biological Process GO:0042752 regulation of circadian rhythm
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:2000779 regulation of double-strand break repair
Biological Process GO:0034097 response to cytokine
Biological Process GO:0001666 response to hypoxia
Biological Process GO:0044790 suppression of viral release by host

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] 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.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[5] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[6] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[7] 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.

[8] 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.