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Q9QYE0 (PLAG1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Zinc finger protein PLAG1
Alternative name(s):
Pleiomorphic adenoma gene 1 protein
Gene names
Name:Plag1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length499 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Transcription factor whose activation results in up-regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation: when overexpressed in cultured cells, higher proliferation rate and transformation are observed. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. Proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland and lipoblastomas. Cooperates with CBFB-MYH11. Ref.8 Ref.9 Ref.11

Subunit structure

Interacts with KPNA2, which escorts protein to the nucleus via interaction with nuclear localization signal. Interacts with E3 SUMO-protein ligase PIAS1, PIAS2 and PIAS4 By similarity.

Subcellular location

Nucleus. Note: Strong nucleolar localization when sumoylation is inhibited By similarity.

Tissue specificity

Expressed in heart, spleen, lung, kidney, brain, testis and epididymis but not in salivary glands. Ref.10

Developmental stage

High fetal expression with a strong decline after birth. Expressed at E9.5 and E10.5 in nervous system with highest level in telencephalon, diencephalon, and midbrain, as well as regionalized expression in the neural tube, which is characteristic of genes involved in the specification of neuronal fates. Ref.7 Ref.10

Domain

C2H2-type zinc fingers 3 interacts with DNA-binding site G-clusterinc fingers. C2H2-type zinc fingers 6 and 7 interact with DNA-binding site core sequence By similarity.

Post-translational modification

Sumoylated with SUMO1; which inhibits transcriptional activity, but does not affect nuclear localization. Blockers of sumoylation pathway such as SENP3 and inactive UBE2I increases transcriptional capacity. Sumoylation is increased in the presence of PIAS1 By similarity.

Acetylated by lysine acetyltransferase EP300; which activates transcriptional capacity. Lysine residues that are sumoylated also seem to be target for acetylation By similarity.

Disruption phenotype

Mice exhibit growth retardation with lower birth weight and disproportionally small seminal vesicles and ventral prostate as well as decreased fertility in both male and female. However, IGFII expression is normal in embryos. Ref.7

Miscellaneous

Mice overexpressing Plag1 develop normally with high Plag1 transgene expression in salivary glands, spleen and weak mammary gland detection. They develop salivary gland tumors with major pathological features of human pleimorphic adenomas at the age of 1-5 months.

Mice with Plag1 overexpression targeted to salivary and mammary gland develop multifocal salivary gland tumors with pathological features of human pleimorphic adenomas at the age of 5 weeks, as well as mammary gland tumors at the age of 1 year. Plag1 overexpression in salivary gland are accompanied by increased IGFII expression. Besides features characteristic of benign pleimorphic adenomas, malignant characteristics are also observed in salivary gland tumors as well as metastasis to the lungs, reinforcing the tumorigenic role of Plag1.

Neonate mice carrying a human myeloid leukemia translocation-associated fusion gene CBFB-MYH11, injected with a retrovirus (4070A), develop the pathology within 2-5 months due to few viral insertions in some genes, such as PLAG1. Insertions near the transcription start site of PLAG1 are predominant in the related tumors and probably participate in the transformation process. Plag1 is one candidate gene that can cooperate with CBFB-MYH11 for leukemogenesis in this mouse model.

Sequence similarities

Belongs to the krueppel C2H2-type zinc-finger protein family.

Contains 7 C2H2-type zinc fingers.

Sequence caution

The sequence BAE22643.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DiseaseProto-oncogene
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
   PTMAcetylation
Isopeptide bond
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processgland morphogenesis

Inferred from mutant phenotype Ref.7. Source: MGI

multicellular organism growth

Inferred from mutant phenotype Ref.7. Source: MGI

negative regulation of gene expression

Inferred from direct assay PubMed 19808959. Source: UniProtKB

organ growth

Inferred from mutant phenotype Ref.7. Source: MGI

positive regulation of gene expression

Inferred from direct assay PubMed 19808959. Source: UniProtKB

positive regulation of glial cell proliferation

Inferred from direct assay PubMed 19808959. Source: UniProtKB

prostate gland growth

Inferred from mutant phenotype Ref.7. Source: MGI

regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: GOC

transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: GOC

   Cellular_componentnucleus

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 499499Zinc finger protein PLAG1
PRO_0000295108

Regions

Zinc finger34 – 5623C2H2-type 1
Zinc finger62 – 8625C2H2-type 2
Zinc finger92 – 11423C2H2-type 3
Zinc finger121 – 14323C2H2-type 4
Zinc finger150 – 17223C2H2-type 5
Zinc finger185 – 20723C2H2-type 6
Zinc finger213 – 23624C2H2-type 7
Region2 – 8483Interacts with KPNA2 By similarity
Region41 – 242202Decreased nuclear import with localization in the nucleus but also in the cytoplasm By similarity
Region243 – 499257Activates transcription; Inhibition of nuclear import due to lack of NLS and KPNA2 interaction By similarity
Region243 – 383141Repression domain; contains 3 sumoylation motifs and massively decrease transcription activity By similarity
Region384 – 499116Massively activates transcription By similarity
Motif22 – 254Nuclear localization signal By similarity
Compositional bias369 – 488120Ser-rich

Amino acid modifications

Cross-link244Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link263Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Sequence conflict4331P → T in AAS86161. Ref.1
Sequence conflict4331P → T in AAF21762. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9QYE0 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: A3493D2DADCB83B2

FASTA49955,579
        10         20         30         40         50         60 
MATVIPGDLS EVRDTQKAPS GKRKRGESKP RKNFPCQLCD KAFNSVEKLK VHSFSHTGER 

        70         80         90        100        110        120 
PYKCTHQDCT KAFVSKYKLQ RHMATHSPEK THKCNYCEKM FHRKDHLKNH LHTHDPNKET 

       130        140        150        160        170        180 
FKCEECGKSY NTKLGFKRHL ALHAATSGDL TCKVCLQNFE STGVLLEHLK SHAGKSSGGV 

       190        200        210        220        230        240 
KEKKHQCEHC ERRFYTRKDV RRHMVVHTGR KDFLCQYCAQ RFGRKDHLTR HMKKSHNQEL 

       250        260        270        280        290        300 
LKVKTEPVDF LDPFTCNMSV PIKDELLPVM SLPSSELLSK PFTNTLQLNL YNTPFQSMQS 

       310        320        330        340        350        360 
SGSAHQMITT LPLGMTCPID MDAVHPSHHL AFKCPFSSTS YAISIPEKEQ PLKGEIESYL 

       370        380        390        400        410        420 
MELQGGAPSS SQDSPASSSK LGLEPQSGSP DDGAGDLSLS KSSISISDPL STPALDFSQL 

       430        440        450        460        470        480 
FNFIPLNGPP YNPLSVGSLG MSYSQEEAHS SVSQLPTQTQ DLQDPANTVG LSSLHSLSAA 

       490 
FTSSLSSSTT LPRFHQAFQ 

« Hide

References

« Hide 'large scale' references
[1]"Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11."
Landrette S.F., Kuo Y.H., Hensen K., van Doorn-Khosrovani S.B., Perrat P.N., Van de Ven W.J., Delwel R., Castilla L.H.
Blood 105:2900-2907(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: 129/SvEv.
Tissue: Embryo.
[2]Hensen K., Voz M.L., Van de Ven W.J.M., Kas K.
Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: 129/Sv.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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].
Tissue: Brain.
[6]"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. expand/collapse author list , 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] OF 324-499.
Strain: C57BL/6J.
Tissue: Egg.
[7]"Targeted disruption of the murine Plag1 proto-oncogene causes growth retardation and reduced fertility."
Hensen K., Braem C., Declercq J., Van Dyck F., Dewerchin M., Fiette L., Denef C., Van de Ven W.J.M.
Dev. Growth Differ. 46:459-470(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE.
[8]"Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia."
Castilla L.H., Perrat P., Martinez N.J., Landrette S.F., Keys R., Oikemus S., Flanegan J., Heilman S., Garrett L., Dutra A., Anderson S., Pihan G.A., Wolff L., Liu P.P.
Proc. Natl. Acad. Sci. U.S.A. 101:4924-4929(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, COOPERATION WITH CBFB-MYH11.
[9]"Salivary gland tumors in transgenic mice with targeted PLAG1 proto-oncogene overexpression."
Declercq J., Van Dyck F., Braem C.V., Van Valckenborgh I.C., Voz M., Wassef M., Schoonjans L., Van Damme B., Fiette L., Van de Ven W.J.M.
Cancer Res. 65:4544-4553(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANSGENIC MICE, FUNCTION.
[10]"Members of the Plag gene family are expressed in complementary and overlapping regions in the developing murine nervous system."
Alam S., Zinyk D., Ma L., Schuurmans C.
Dev. Dyn. 234:772-782(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[11]"Wnt pathway is involved in pleomorphic adenomas induced by overexpression of PLAG1 in transgenic mice."
Zhao X., Ren W., Yang W., Wang Y., Kong H., Wang L., Yan L., Xu G., Fei J., Fu J., Zhang C., Wang Z.
Int. J. Cancer 118:643-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANSGENIC MICE, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY574219 mRNA. Translation: AAS86161.1.
AF057366 mRNA. Translation: AAF21762.1.
BC139283 mRNA. Translation: AAI39284.1.
BC139285 mRNA. Translation: AAI39286.1.
AL807387 Genomic DNA. Translation: CAM18646.1.
CH466538 Genomic DNA. Translation: EDL05712.1.
AK135759 mRNA. Translation: BAE22643.1. Different initiation.
CCDSCCDS17941.1.
RefSeqNP_064353.2. NM_019969.3.
XP_006538179.1. XM_006538116.1.
XP_006538180.1. XM_006538117.1.
XP_006538181.1. XM_006538118.1.
XP_006538182.1. XM_006538119.1.
UniGeneMm.331467.

3D structure databases

ProteinModelPortalQ9QYE0.
SMRQ9QYE0. Positions 32-239.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ9QYE0.

Proteomic databases

PRIDEQ9QYE0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000003369; ENSMUSP00000003369; ENSMUSG00000003282.
GeneID56711.
KEGGmmu:56711.
UCSCuc008rwp.2. mouse.

Organism-specific databases

CTD5324.
MGIMGI:1891916. Plag1.

Phylogenomic databases

eggNOGCOG5048.
GeneTreeENSGT00390000013640.
HOGENOMHOG000294191.
HOVERGENHBG053608.
InParanoidB1AXC4.
OMAIDMDAVH.
OrthoDBEOG71K62Q.
TreeFamTF332024.

Gene expression databases

BgeeQ9QYE0.
CleanExMM_PLAG1.
GenevestigatorQ9QYE0.

Family and domain databases

Gene3D3.30.160.60. 5 hits.
InterProIPR027775. C2H2_Znf_fam.
IPR027765. PLAG1.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERPTHR10032. PTHR10032. 1 hit.
PTHR10032:SF124. PTHR10032:SF124. 1 hit.
PfamPF00096. zf-C2H2. 1 hit.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 7 hits.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 7 hits.
PS50157. ZINC_FINGER_C2H2_2. 7 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio313179.
PROQ9QYE0.
SOURCESearch...

Entry information

Entry namePLAG1_MOUSE
AccessionPrimary (citable) accession number: Q9QYE0
Secondary accession number(s): B1AXC4, Q3UXC0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 10, 2007
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot