Q60953 (PML_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein PML

Gene names

Name:

Pml

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	885 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum. Regulates RB1 phosphorylation and activity. Acts as both a negative regulator of PPARGC1A acetylation and a potent activator of PPAR signaling and fatty acid oxidation. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates PER2 nuclear localization and circadian function. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. Required for normal development of the brain cortex during embryogenesis. Plays a role in granulopoiesis or monopoiesis of myeloid progenitor cells. May play a role regulating stem and progenitor cell fate in tissues as diverse as blood, brain and breast. Shows antiviral activity towards lymphocytic choriomeningitis virus (LCMV) and the vesicular stomatitis virus (VSV). Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.12 Ref.14 Ref.15 Ref.16 Ref.22 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28 Ref.29
Subunit structure	Key component of PML bodies. PML bodies are formed by the interaction of PML homodimers (via SUMO-binding motif) with sumoylated PML, leading to the assembly of higher oligomers. Several types of PML bodies have been observed. PML bodies can form hollow spheres that can sequester target proteins inside. Interacts (via SUMO-binding motif) with sumoylated proteins. Interacts (via C-terminus) with p53/TP53. Recruits p53/TP53 and CHEK2 into PML bodies, which promotes p53/TP53 phosphorylation at 'Ser-20' and prevents its proteasomal degradation. Interacts with MDM2, and sequesters MDM2 in the nucleolus, thereby preventing ubiquitination of p53/TP53. Interaction with PML-RARA oncoprotein and certain viral proteins causes disassembly of PML bodies and abolishes the normal PML function. Interacts with TERT, SIRT1, TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C-terminus). Interacts with Lassa virus Z protein and rabies virus phosphoprotein. Interacts (in the cytoplasm) with TGFBR1, TGFBR2 and PKM. Interacts (via the coiled-coil domain and when sumoylated) with SATB1. Interacts with UBE2I; the interaction is enhanced by arsenic binding. Interacts with SMAD2, SMAD3, DAXX, RPL11, HIPK2 and MTOR By similarity. Interacts with ITPR3, PPP1A and RB1. Interacts with RNF4, NLRP3, MAGEA2, RBL2, PER2, E2F4 and MAPK7/BMK1. Interacts with CSNK2A1 and CSNK2A3 By similarity. Interacts with PPARGC1A AND KAT2A. Ref.8 Ref.11 Ref.13 Ref.14 Ref.16 Ref.22 Ref.23 Ref.29
Subcellular location	Nucleus By similarity. Nucleus › nucleoplasm. Cytoplasm. Nucleus › PML body. Nucleus › nucleolus By similarity. Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Detected in the nucleolus after DNA damage. Acetylation at Lys-497 is essential for its nuclear localization. Within the nucleus, most of PML is expressed in the diffuse nuclear fraction of the nucleoplasm and only a small fraction is found in the matrix-associated nuclear bodies (PML-NBs). The transfer of PML from the nucleoplasm to PML-NBs depends on its phosphorylation and sumoylation. The B1 box and the RING finger are also required for the localization in PML-NBs. Also found in specific membrane structures termed mitochondria-associated membranes (MAMs) which connect the endoplasmic reticulum (ER) and the mitochondria By similarity. Ref.8 Ref.14 Ref.23 Ref.27 Ref.29
Domain	The coiled-coil domain mediates a strong homo/multidimerization activity essential for core assembly of PML-NBs By similarity. Binds arsenic via the RING-type zinc finger By similarity. The Sumo interaction motif (SIM) is required for efficient ubiquitination, recruitment of proteasome components within PML-NBs and PML degradation in response to arsenic trioxide By similarity.
Post-translational modification	Ubiquitinated; mediated by RNF4, UHRF1, UBE3A/E6AP, KLHL20-based E3 ligase complex, SIAH1 or SIAH2 and leading to subsequent proteasomal degradation. Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent. Ubiquitination by KLHL20-based E3 ligase complex requires CDK1/2-mediated phosphorylation at Ser-528 which in turn is recognized by prolyl-isopeptidase PIN1 and PIN1-catalyzed isomerization further potentiates PML interaction with KLHL20 By similarity. Ref.13 Sumoylation regulates PML's: stability in response to extracellular or intracellular stimuli, transcription directly and indirectly, through sequestration of or dissociation of the transcription factors from PML-NBs, ability to regulate apoptosis and its anti-viral activities. It is also essential for: maintaining proper PML nuclear bodies (PML-NBs) structure and normal function, recruitment of components of PML-NBs, the turnover and retention of PML in PML-NBs and the integrity of PML-NBs. Undergoes 'Lys-11'-linked sumoylation. Sumoylation on all three sites (Lys-70, Lys-165 and Lys-500) is required for nuclear body formation. Sumoylation on Lys-165 is a prerequisite for sumoylation on Lys-70. Lys-70 and Lys-165 are sumoylated by PISA1 and PIAS2. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-575 which in turn triggers its ubiquitin-mediated degradation. Sumoylation at Lys-500 by RANBP2 is essential for the proper assembly of PML-NBs. Desumoylated by SENP1, SENP2, SENP3, SENP5 and SENP6 By similarity. Ref.8 Phosphorylation is a major regulatory mechanism that controls PML protein abundance and the number and size of PML nuclear bodies (PML-NBs). Phosphorylated in response to DNA damage, probably by ATR. HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage. MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-dependent PML degradation. CK2-mediated phosphorylation at Ser-575 primes PML ubiquitination via an unidentified ubiquitin ligase By similarity. Acetylation at Lys-497 is essential for its nuclear localization. Deacetylated at Lys-497 by SIRT1 and this deacetylation promotes PML control of PER2 nuclear localization By similarity.
Disruption phenotype	Mice are born at the expected Mendelian rate and are fertile. They show leukopenia with reduced levels of circulating granulocytes and myeloid cells. They are highly susceptible to infections, causing a reduced life span. Mice do not exhibit normal apoptosis of hematopoietic stem cells after DNA damage due to irradiation. They do not exhibit normal apoptosis in response to FAS, TNF, TGFB1, interferons and ceramide, and show impaired activation of caspases in response to pro-apoptotic stimuli. Mice are highly susceptible to chemical carcinogens. Mice display accelerated revascularization after ischemia. Newborns have smaller brains with a reduced size of the brain cortex. Cultured embryonic fibroblasts show impaired growth inhibition by retinoic acid, and are defective in the activation of CDKN1A in response to retinoic acid. Mice display aberrant learning and memory, lower levels of anxiety-like behavior and specific deficits in long-term plasticity. Ref.5 Ref.6 Ref.10 Ref.16 Ref.22 Ref.28
Sequence similarities	Contains 2 B box-type zinc fingers. Contains 1 RING-type zinc finger.
Sequence caution	The sequence AAA97601.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Antiviral defense Apoptosis Host-virus interaction Immunity Innate immunity Transcription Transcription regulation
Cellular component	Cytoplasm Endoplasmic reticulum Endosome Membrane Nucleus
Coding sequence diversity	Alternative splicing
Disease	Tumor suppressor
Domain	Coiled coil Repeat Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator
PTM	Acetylation Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Inferred from mutant phenotype PubMed 15626733. Source: UniProtKB PML body organization Inferred from direct assay PubMed 12529400. Source: MGI SMAD protein import into nucleus Inferred from mutant phenotype Ref.15. Source: MGI activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from mutant phenotype Ref.5. Source: MGI branching involved in mammary gland duct morphogenesis Inferred from mutant phenotype PubMed 19261859. Source: MGI cell cycle arrest Inferred from mutant phenotype PubMed 10910364. Source: UniProtKB cell fate commitment Inferred from mutant phenotype PubMed 19261859. Source: MGI cellular response to interleukin-4 Inferred from direct assay PubMed 9798653. Source: MGI cellular senescence Inferred from sequence or structural similarity. Source: UniProtKB common-partner SMAD protein phosphorylation Inferred from mutant phenotype Ref.15. Source: MGI defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW endoplasmic reticulum calcium ion homeostasis Inferred from mutant phenotype Ref.23. Source: UniProtKB induction of apoptosis Inferred from mutant phenotype PubMed 10684855Ref.23. Source: UniProtKB innate immune response Inferred from electronic annotation. Source: UniProtKB-KW intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from mutant phenotype PubMed 15626733. Source: UniProtKB maintenance of protein location in nucleus Inferred from sequence orthology PubMed 17332504. Source: MGI myeloid cell differentiation Inferred from mutant phenotype Ref.6. Source: MGI negative regulation of angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell growth Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell proliferation Inferred from mutant phenotype Ref.6. Source: MGI negative regulation of mitotic cell cycle Inferred from electronic annotation. Source: Compara negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara negative regulation of telomerase activity Inferred from electronic annotation. Source: Compara negative regulation of telomere maintenance via telomerase Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of translation in response to oxidative stress Inferred from electronic annotation. Source: Compara positive regulation of defense response to virus by host Inferred from electronic annotation. Source: Compara positive regulation of extrinsic apoptotic signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of histone deacetylation Inferred from sequence or structural similarity. Source: UniProtKB proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB protein complex assembly Inferred from sequence or structural similarity. Source: UniProtKB protein stabilization Inferred from electronic annotation. Source: Compara regulation of MHC class I biosynthetic process Inferred from direct assay PubMed 9845074. Source: MGI regulation of calcium ion transport into cytosol Inferred from mutant phenotype Ref.23. Source: UniProtKB regulation of double-strand break repair Inferred from sequence or structural similarity. Source: UniProtKB regulation of protein phosphorylation Inferred from mutant phenotype Ref.23. Source: UniProtKB response to UV Inferred from mutant phenotype PubMed 15626733. Source: MGI response to gamma radiation Inferred from mutant phenotype PubMed 11025664Ref.5. Source: MGI response to hypoxia Inferred from sequence or structural similarity. Source: UniProtKB retinoic acid receptor signaling pathway Inferred from mutant phenotype Ref.6. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Inferred from mutant phenotype Ref.15. Source: MGI virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	PML body Inferred from mutant phenotype Ref.8. Source: UniProtKB cytosol Inferred from direct assay Ref.23. Source: UniProtKB early endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extrinsic to endoplasmic reticulum membrane Inferred from direct assay Ref.23. Source: UniProtKB nuclear matrix Inferred from direct assay PubMed 15252119. Source: MGI nuclear membrane Inferred from electronic annotation. Source: Compara nucleolus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW SMAD binding Inferred from direct assay Ref.15. Source: MGI cobalt ion binding Inferred from electronic annotation. Source: Compara transcription coactivator activity Traceable author statement PubMed 15626733. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Axin1	Q14DJ8	4	EBI-4406901,EBI-4312125
Fas	P25446	6	EBI-3895605,EBI-296206

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q60953-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q60953-2)

The sequence of this isoform differs from the canonical sequence as follows:
     431-476: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 885	885	Protein PML		PRO_0000056002
Regions
	Zinc finger	62 – 97	36	RING-type
	Zinc finger	129 – 171	43	B box-type 1
	Zinc finger	188 – 239	52	B box-type 2
	Region	458 – 565	108	Interaction with PER2 By similarity
	Region	486 – 500	15	Nuclear localization signal By similarity
	Region	566 – 572	7	Sumo interaction motif (SIM) By similarity
	Coiled coil	295 – 331	37	Potential
	Compositional bias	12 – 38	27	Pro-rich
Sites
	Metal binding	62	1	Zinc 1 By similarity
	Metal binding	65	1	Zinc 1 By similarity
	Metal binding	77	1	Zinc 2 By similarity
	Metal binding	79	1	Zinc 2 By similarity
	Metal binding	82	1	Zinc 1 By similarity
	Metal binding	85	1	Zinc 1 By similarity
	Metal binding	93	1	Zinc 2 By similarity
	Metal binding	96	1	Zinc 2 By similarity
Amino acid modifications
	Modified residue	17	1	Phosphoserine; by HIPK2 Ref.18
	Modified residue	45	1	Phosphoserine; by HIPK2 and MAPK1 By similarity
	Modified residue	47	1	Phosphoserine; by HIPK2 and MAPK1 By similarity
	Modified residue	404	1	Phosphoserine; by MAPK1 and MAPK7 By similarity
	Modified residue	497	1	N6-acetyllysine By similarity
	Modified residue	514	1	Phosphoserine Ref.17
	Modified residue	515	1	Phosphoserine; by MAPK1 Ref.17
	Modified residue	525	1	N6-acetyllysine By similarity
	Modified residue	527	1	Phosphothreonine Ref.17
	Modified residue	528	1	Phosphoserine; by CDK1 and CDK2 Ref.17 Ref.21
	Modified residue	540	1	Phosphoserine; by MAPK1 By similarity
	Modified residue	556	1	Phosphothreonine Ref.17
	Modified residue	575	1	Phosphoserine; by CK2 By similarity
	Modified residue	609	1	Phosphoserine Ref.19
	Cross-link	70		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	165		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	384		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	486		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
	Cross-link	500		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Natural variations
	Alternative sequence	431 – 476	46	Missing in isoform 2.		VSP_026028
Experimental info
	Sequence conflict	210	1	G → V in BAC25716. Ref.1
	Sequence conflict	414	1	A → V in BAC25716. Ref.1
	Sequence conflict	424	1	T → S in BAC25716. Ref.1
	Sequence conflict	429	1	E → V in AAH20990. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 29, 2007. Version 3. Checksum: 6A2F93F4CD482FDD	FASTA	885	98,242
	10 20 30 40 50 60 METEPVSVQK VPAPPGSPCR QQDSALTPTP TMPPPEEPSE DYEHSQSPAE QAIQEEFQFL 70 80 90 100 110 120 RCPSCQAQAK CPKLLPCLHT LCSGCLEAPG LQCPICKAPG QADANGEALD NVFFESLQRR 130 140 150 160 170 180 LAVFRQIVDA QAACTRCKGL ADFWCFECEQ LICSKCFEAH QWYLKHEARP LADLRDNSVS 190 200 210 220 230 240 SFLDSTRKSN IFCSNTNHRN PALTDIYCRG CAKPLCCTCA LLDRNHSHLH CDIGEEIQQW 250 260 270 280 290 300 HEELGTMTQT LEEQGRTFDS AHAQMCSAIG QLDHARADIE KQIRARVRQV VDYVQAQERE 310 320 330 340 350 360 LLEAVNDRYQ RDYQEIAGQL SCLEAVLQRI RTSGALVKRM KLYASDQEVL DMHSFLRKAL 370 380 390 400 410 420 CSLRQEEPQN QKVQLLTRGF EEFKLCLQDF ISCITQRINA AVASPEAASN QPEAASTHPV 430 440 450 460 470 480 TTSTPEDLEQ PKEVQSVQAQ ALELSKTQPV AMVKTVPGAH PVPVYAFSMQ GPTYREEASQ 490 500 510 520 530 540 TVGSMKRKCS HEDCSRKIIK MESTEENEDR LATSSPEQSW PSTFKATSPP HLDGTSNPES 550 560 570 580 590 600 TVPEKKILLP NNNHVTSDTG ETEERVVVIS SSEDSDTENL SSHELDDSSS ESSSLQLEGP 610 620 630 640 650 660 NSLKALDESL AEPHLEDRTL VFFDLKIDNE TQKISQLAAV NRESKFRVLI QPEAFSVYSK 670 680 690 700 710 720 AVSLEAGLRH FLSFLTTMHR PILACSRLWG PGLPIFFQTL SDINKLWEFQ DTISGFLAVL 730 740 750 760 770 780 PLIRERIPGA SSFKLGNLAK TYLARNMSER SALASVLAMR DLCCLLEISP GLPLAQHIYS 790 800 810 820 830 840 FSSLQCFASL QPLIQASVLP QSEARLLALH NVSFVELLNA YRTNRQEGLK KYVHYLSLQT 850 860 870 880 TPLSSSASTQ VAQFLQALST HMEGLLEGHA PAGAEGKAES KGCLA
	Isoform 2 [UniParc]. Checksum: AA1B497B0C2559E3	FASTA	839	93,263
	10 20 30 40 50 60 METEPVSVQK VPAPPGSPCR QQDSALTPTP TMPPPEEPSE DYEHSQSPAE QAIQEEFQFL 70 80 90 100 110 120 RCPSCQAQAK CPKLLPCLHT LCSGCLEAPG LQCPICKAPG QADANGEALD NVFFESLQRR 130 140 150 160 170 180 LAVFRQIVDA QAACTRCKGL ADFWCFECEQ LICSKCFEAH QWYLKHEARP LADLRDNSVS 190 200 210 220 230 240 SFLDSTRKSN IFCSNTNHRN PALTDIYCRG CAKPLCCTCA LLDRNHSHLH CDIGEEIQQW 250 260 270 280 290 300 HEELGTMTQT LEEQGRTFDS AHAQMCSAIG QLDHARADIE KQIRARVRQV VDYVQAQERE 310 320 330 340 350 360 LLEAVNDRYQ RDYQEIAGQL SCLEAVLQRI RTSGALVKRM KLYASDQEVL DMHSFLRKAL 370 380 390 400 410 420 CSLRQEEPQN QKVQLLTRGF EEFKLCLQDF ISCITQRINA AVASPEAASN QPEAASTHPV 430 440 450 460 470 480 TTSTPEDLEQ EASQTVGSMK RKCSHEDCSR KIIKMESTEE NEDRLATSSP EQSWPSTFKA 490 500 510 520 530 540 TSPPHLDGTS NPESTVPEKK ILLPNNNHVT SDTGETEERV VVISSSEDSD TENLSSHELD 550 560 570 580 590 600 DSSSESSSLQ LEGPNSLKAL DESLAEPHLE DRTLVFFDLK IDNETQKISQ LAAVNRESKF 610 620 630 640 650 660 RVLIQPEAFS VYSKAVSLEA GLRHFLSFLT TMHRPILACS RLWGPGLPIF FQTLSDINKL 670 680 690 700 710 720 WEFQDTISGF LAVLPLIRER IPGASSFKLG NLAKTYLARN MSERSALASV LAMRDLCCLL 730 740 750 760 770 780 EISPGLPLAQ HIYSFSSLQC FASLQPLIQA SVLPQSEARL LALHNVSFVE LLNAYRTNRQ 790 800 810 820 830 EGLKKYVHYL SLQTTPLSSS ASTQVAQFLQ ALSTHMEGLL EGHAPAGAEG KAESKGCLA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Lung.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: FVB/N. Tissue: Salivary gland.
[3]	"Cloning of the murine homolog of the leukemia-associated PML gene." Goddard A.D., Yuan J.Q., Fairbairn L., Dexter M., Borrow J., Kozak C., Solomon E. Mamm. Genome 6:732-737(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-839 (ISOFORM 2).
[4]	Goddard A.D., Howe K., Solomon E. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 130; 212; 284; 638; 731; 750; 770-772; 820 AND 839.
[5]	"PML is essential for multiple apoptotic pathways." Wang Z.G., Ruggero D., Ronchetti S., Zhong S., Gaboli M., Rivi R., Pandolfi P.P. Nat. Genet. 20:266-272(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[6]	"Role of PML in cell growth and the retinoic acid pathway." Wang Z.G., Delva L., Gaboli M., Rivi R., Giorgio M., Cordon-Cardo C., Grosveld F., Pandolfi P.P. Science 279:1547-1551(1998) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[7]	"A role for PML and the nuclear body in genomic stability." Zhong S., Hu P., Ye T.Z., Stan R., Ellis N.A., Pandolfi P.P. Oncogene 18:7941-7947(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Role of SUMO-1-modified PML in nuclear body formation." Zhong S., Muller S., Ronchetti S., Freemont P.S., Dejean A., Pandolfi P.P. Blood 95:2748-2752(2000) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION, SUBCELLULAR LOCATION, SUBUNIT.
[9]	"Effects of promyelocytic leukemia protein on virus-host balance." Bonilla W.V., Pinschewer D.D., Klenerman P., Rousson V., Gaboli M., Pandolfi P.P., Zinkernagel R.M., Salvato M.S., Hengartner H. J. Virol. 76:3810-3818(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN LCMV AND VSV RESTRICTION.
[10]	"Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies." Blondel D., Regad T., Poisson N., Pavie B., Harper F., Pandolfi P.P., De The H., Chelbi-Alix M.K. Oncogene 21:7957-7970(2002) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[11]	"Forced expression of RNF36 induces cell apoptosis." Shyu H.-W., Hsu S.-H., Hsieh-Li H.-M., Li H. Exp. Cell Res. 287:301-313(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRIM69.
[12]	"Impairment of p53 acetylation, stability and function by an oncogenic transcription factor." Insinga A., Monestiroli S., Ronzoni S., Carbone R., Pearson M., Pruneri G., Viale G., Appella E., Pelicci P., Minucci S. EMBO J. 23:1144-1154(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"The coiled-coil domain is the structural determinant for mammalian homologues of Drosophila Sina-mediated degradation of promyelocytic leukemia protein and other tripartite motif proteins by the proteasome." Fanelli M., Fantozzi A., De Luca P., Caprodossi S., Matsuzawa S., Lazar M.A., Pelicci P.G., Minucci S. J. Biol. Chem. 279:5374-5379(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIAH2, DEGRADATION.
[14]	"PML regulates p53 stability by sequestering Mdm2 to the nucleolus." Bernardi R., Scaglioni P.P., Bergmann S., Horn H.F., Vousden K.H., Pandolfi P.P. Nat. Cell Biol. 6:665-672(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MDM2 AND RPL11, SUBCELLULAR LOCATION.
[15]	"Cytoplasmic PML function in TGF-beta signalling." Lin H.K., Bergmann S., Pandolfi P.P. Nature 431:205-211(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR." Bernardi R., Guernah I., Jin D., Grisendi S., Alimonti A., Teruya-Feldstein J., Cordon-Cardo C., Simon M.C., Rafii S., Pandolfi P.P. Nature 442:779-785(2006) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION, INTERACTION WITH MTOR.
[17]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-514; SER-515; THR-527; SER-528 AND THR-556, MASS SPECTROMETRY. Tissue: Liver.
[18]	"Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis." Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H. J. Proteome Res. 7:3957-3967(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, MASS SPECTROMETRY. Tissue: Liver.
[19]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-609, MASS SPECTROMETRY. Tissue: Melanoma.
[20]	"PML: a tumor suppressor that regulates cell fate in mammary gland." Li W., Rich T., Watson C.J. Cell Cycle 8:2711-2717(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[21]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[22]	"The tumor suppressor Pml regulates cell fate in the developing neocortex." Regad T., Bellodi C., Nicotera P., Salomoni P. Nat. Neurosci. 12:132-140(2009) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, INTERACTION WITH RB1, FUNCTION.
[23]	"PML regulates apoptosis at endoplasmic reticulum by modulating calcium release." Giorgi C., Ito K., Lin H.K., Santangelo C., Wieckowski M.R., Lebiedzinska M., Bononi A., Bonora M., Duszynski J., Bernardi R., Rizzuto R., Tacchetti C., Pinton P., Pandolfi P.P. Science 330:1247-1251(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ITPR3, SUBCELLULAR LOCATION.
[24]	"A role for PML in innate immunity." Lunardi A., Gaboli M., Giorgio M., Rivi R., Bygrave A., Antoniou M., Drabek D., Dzierzak E., Fagioli M., Salmena L., Botto M., Cordon-Cardo C., Luzzatto L., Pelicci P.G., Grosveld F., Pandolfi P.P. Genes Cancer 2:10-19(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[25]	"PML is a key component for the differentiation of myeloid progenitor cells to macrophages." Khalfin-Rabinovich Y., Weinstein A., Levi B.Z. Int. Immunol. 23:287-296(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[26]	"The role of PML in the nervous system." Salomoni P., Betts-Henderson J. Mol. Neurobiol. 43:114-123(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[27]	"PML regulates PER2 nuclear localization and circadian function." Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A., Zhao Z., Lee C.C., Chang K.S. EMBO J. 31:1427-1439(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[28]	"Impaired cognitive function and reduced anxiety-related behavior in a promyelocytic leukemia (PML) tumor suppressor protein-deficient mouse." Butler K., Martinez L.A., Tejada-Simon M.V. Genes Brain Behav. 0:0-0(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[29]	"A metabolic prosurvival role for PML in breast cancer." Carracedo A., Weiss D., Leliaert A.K., Bhasin M., de Boer V.C., Laurent G., Adams A.C., Sundvall M., Song S.J., Ito K., Finley L.S., Egia A., Libermann T., Gerhart-Hines Z., Puigserver P., Haigis M.C., Maratos-Flier E., Richardson A.L., Schafer Z.T., Pandolfi P.P. J. Clin. Invest. 122:3088-3100(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PPARGC1A AND KAT2A.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK028044 mRNA. Translation: BAC25716.1. BC020990 mRNA. Translation: AAH20990.2. U33626 mRNA. Translation: AAA97601.2. Different initiation.
IPI	IPI00122615. IPI00229072.
RefSeq	NP_032910.3. NM_008884.5. NP_835188.2. NM_178087.4.
UniGene	Mm.392123.
3D structure databases
ProteinModelPortal	Q60953.
SMR	Q60953. Positions 54-109.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-29279N.
IntAct	Q60953. 8 interactions.
MINT	MINT-4108085.
PTM databases
PhosphoSite	Q60953.
Proteomic databases
PaxDb	Q60953.
PRIDE	Q60953.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000085673; ENSMUSP00000082816; ENSMUSG00000036986. ENSMUST00000114136; ENSMUSP00000109771; ENSMUSG00000036986.
GeneID	18854.
KEGG	mmu:18854.
UCSC	uc009pwp.2. mouse. uc009pwq.2. mouse.
Organism-specific databases
CTD	5371.
MGI	MGI:104662. Pml.
Phylogenomic databases
eggNOG	NOG326718.
GeneTree	ENSGT00510000048454.
HOGENOM	HOG000115586.
HOVERGEN	HBG000552.
InParanoid	Q60953.
KO	K10054.
OMA	VQRMKRY.
OrthoDB	EOG4H19V2.
Gene expression databases
ArrayExpress	Q60953.
Bgee	Q60953.
CleanEx	MM_PML.
Genevestigator	Q60953.
GermOnline	ENSMUSG00000036986. Mus musculus.
Family and domain databases
Gene3D	3.30.40.10. 1 hit.
InterPro	IPR021978. DUF3583. IPR000315. Znf_B-box. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. IPR017907. Znf_RING_CS. [Graphical view]
Pfam	PF12126. DUF3583. 1 hit. PF00643. zf-B_box. 1 hit. [Graphical view]
SMART	SM00336. BBOX. 1 hit. SM00184. RING. 1 hit. [Graphical view]
PROSITE	PS50119. ZF_BBOX. 2 hits. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	PML. mouse.
NextBio	295230.
SOURCE	Search...

Entry information

Entry name

PML_MOUSE

Accession

Primary (citable) accession number: Q60953
Secondary accession number(s): Q8CEJ1, Q8VCC4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 29, 2007
Last modified:	May 29, 2013
This is version 129 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program