CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005798
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein PML 
Protein Synonyms/Alias
 Promyelocytic leukemia protein; RING finger protein 71; Tripartite motif-containing protein 19 
Gene Name
 PML 
Gene Synonyms/Alias
 MYL; PP8675; RNF71; TRIM19 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
401KDAAVSKKASPEAASubiquitination[1]
428SNTTTAQKRKCSQTQubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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. 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-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration. 
Sequence Annotation
 ZN_FING 57 92 RING-type.
 ZN_FING 124 166 B box-type 1; atypical.
 ZN_FING 183 236 B box-type 2.
 REGION 448 555 Interaction with PER2.
 REGION 476 490 Nuclear localization signal.
 REGION 556 562 Sumo interaction motif (SIM).
 METAL 57 57 Zinc 1.
 METAL 60 60 Zinc 1.
 METAL 72 72 Zinc 2.
 METAL 74 74 Zinc 2.
 METAL 77 77 Zinc 1.
 METAL 80 80 Zinc 1.
 METAL 88 88 Zinc 2.
 METAL 91 91 Zinc 2.
 MOD_RES 8 8 Phosphoserine; by HIPK2.
 MOD_RES 28 28 Phosphothreonine; by MAPK1.
 MOD_RES 36 36 Phosphoserine; by HIPK2 and MAPK1.
 MOD_RES 38 38 Phosphoserine; by HIPK2 and MAPK1.
 MOD_RES 40 40 Phosphoserine; by MAPK1.
 MOD_RES 42 42 Phosphothreonine.
 MOD_RES 117 117 Phosphoserine; by CHEK2.
 MOD_RES 403 403 Phosphoserine; by MAPK1 and MAPK7.
 MOD_RES 409 409 Phosphothreonine; by MAPK7.
 MOD_RES 487 487 N6-acetyllysine.
 MOD_RES 504 504 Phosphoserine (By similarity).
 MOD_RES 505 505 Phosphoserine; by MAPK1.
 MOD_RES 515 515 N6-acetyllysine (Probable).
 MOD_RES 518 518 Phosphoserine; by CDK1 and CDK2.
 MOD_RES 527 527 Phosphoserine; by MAPK1.
 MOD_RES 530 530 Phosphoserine; by MAPK1.
 MOD_RES 535 535 Phosphoserine.
 MOD_RES 565 565 Phosphoserine; by CK2.
 CROSSLNK 65 65 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 160 160 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 380 380 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 400 400 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 401 401 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 476 476 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 490 490 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 497 497 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; Activator; Alternative splicing; Antiviral defense; Apoptosis; Chromosomal rearrangement; Coiled coil; Complete proteome; Cytoplasm; DNA-binding; Endoplasmic reticulum; Endosome; Host-virus interaction; Immunity; Innate immunity; Isopeptide bond; Membrane; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Repeat; Transcription; Transcription regulation; Tumor suppressor; Ubl conjugation; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 882 AA 
Protein Sequence
MEPAPARSPR PQQDPARPQE PTMPPPETPS EGRQPSPSPS PTERAPASEE EFQFLRCQQC 60
QAEAKCPKLL PCLHTLCSGC LEASGMQCPI CQAPWPLGAD TPALDNVFFE SLQRRLSVYR 120
QIVDAQAVCT RCKESADFWC FECEQLLCAK CFEAHQWFLK HEARPLAELR NQSVREFLDG 180
TRKTNNIFCS NPNHRTPTLT SIYCRGCSKP LCCSCALLDS SHSELKCDIS AEIQQRQEEL 240
DAMTQALQEQ DSAFGAVHAQ MHAAVGQLGR ARAETEELIR ERVRQVVAHV RAQERELLEA 300
VDARYQRDYE EMASRLGRLD AVLQRIRTGS ALVQRMKCYA SDQEVLDMHG FLRQALCRLR 360
QEEPQSLQAA VRTDGFDEFK VRLQDLSSCI TQGKDAAVSK KASPEAASTP RDPIDVDLDV 420
SNTTTAQKRK CSQTQCPRKV IKMESEEGKE ARLARSSPEQ PRPSTSKAVS PPHLDGPPSP 480
RSPVIGSEVF LPNSNHVASG AGEAEERVVV ISSSEDSDAE NSSSRELDDS SSESSDLQLE 540
GPSTLRVLDE NLADPQAEDR PLVFFDLKID NETQKISQLA AVNRESKFRV VIQPEAFFSI 600
YSKAVSLEVG LQHFLSFLSS MRRPILACYK LWGPGLPNFF RALEDINRLW EFQEAISGFL 660
AALPLIRERV PGASSFKLKN LAQTYLARNM SERSAMAAVL AMRDLCRLLE VSPGPQLAQH 720
VYPFSSLQCF ASLQPLVQAA VLPRAEARLL ALHNVSFMEL LSAHRRDRQG GLKKYSRYLS 780
LQTTTLPPAQ PAFNLQALGT YFEGLLEGPA LARAEGVSTP LAGRGLAERA SQQS 834 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005829; C:cytosol; ISS:UniProtKB.
 GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
 GO:0042406; C:extrinsic to endoplasmic reticulum membrane; ISS:UniProtKB.
 GO:0016363; C:nuclear matrix; IDA:UniProtKB.
 GO:0031965; C:nuclear membrane; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0016605; C:PML body; IDA:UniProtKB.
 GO:0050897; F:cobalt ion binding; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
 GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Compara.
 GO:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Compara.
 GO:0007050; P:cell cycle arrest; IDA:UniProtKB.
 GO:0045165; P:cell fate commitment; IEA:Compara.
 GO:0090398; P:cellular senescence; IDA:UniProtKB.
 GO:0007182; P:common-partner SMAD protein phosphorylation; IEA:Compara.
 GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
 GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; ISS:UniProtKB.
 GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISS:UniProtKB.
 GO:0006917; P:induction of apoptosis; IDA:UniProtKB.
 GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
 GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB.
 GO:0051457; P:maintenance of protein location in nucleus; IDA:MGI.
 GO:0030099; P:myeloid cell differentiation; IEA:Compara.
 GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
 GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IMP:BHF-UCL.
 GO:0045930; P:negative regulation of mitotic cell cycle; IDA:UniProtKB.
 GO:2000059; P:negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
 GO:0051974; P:negative regulation of telomerase activity; IMP:UniProtKB.
 GO:0032211; P:negative regulation of telomere maintenance via telomerase; IMP:UniProtKB.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0032938; P:negative regulation of translation in response to oxidative stress; IDA:UniProtKB.
 GO:0030578; P:PML body organization; IDA:UniProtKB.
 GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB.
 GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0031065; P:positive regulation of histone deacetylation; IDA:UniProtKB.
 GO:0043161; P:proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
 GO:0006461; P:protein complex assembly; IDA:UniProtKB.
 GO:0050821; P:protein stabilization; IDA:UniProtKB.
 GO:0006605; P:protein targeting; IDA:UniProtKB.
 GO:0010522; P:regulation of calcium ion transport into cytosol; ISS:UniProtKB.
 GO:2000779; P:regulation of double-strand break repair; IMP:UniProtKB.
 GO:0045343; P:regulation of MHC class I biosynthetic process; IEA:Compara.
 GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
 GO:0010332; P:response to gamma radiation; IEA:Compara.
 GO:0001666; P:response to hypoxia; IDA:UniProtKB.
 GO:0009411; P:response to UV; IEA:Compara.
 GO:0048384; P:retinoic acid receptor signaling pathway; IEA:Compara.
 GO:0007184; P:SMAD protein import into nucleus; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Compara.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR021978; DUF3583.
 IPR000315; Znf_B-box.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD.
 IPR017907; Znf_RING_CS. 
Pfam
 PF12126; DUF3583
 PF00643; zf-B_box 
SMART
 SM00336; BBOX
 SM00184; RING 
PROSITE
 PS50119; ZF_BBOX
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 
PRINTS