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Q9QYE0

- PLAG1_MOUSE

UniProt

Q9QYE0 - PLAG1_MOUSE

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Protein

Zinc finger protein PLAG1

Gene

Plag1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

Functioni

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-MYH11.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri34 – 5623C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri62 – 8625C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri92 – 11423C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri121 – 14323C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri150 – 17223C2H2-type 5PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri185 – 20723C2H2-type 6PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri213 – 23624C2H2-type 7PROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. metal ion binding Source: UniProtKB-KW
  2. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: Ensembl
  3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  4. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: RefGenome

GO - Biological processi

  1. gland morphogenesis Source: MGI
  2. multicellular organism growth Source: MGI
  3. negative regulation of gene expression Source: UniProtKB
  4. organ growth Source: MGI
  5. positive regulation of gene expression Source: UniProtKB
  6. positive regulation of glial cell proliferation Source: UniProtKB
  7. prostate gland growth Source: MGI
  8. transcription from RNA polymerase II promoter Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Zinc finger protein PLAG1
Alternative name(s):
Pleiomorphic adenoma gene 1 protein
Gene namesi
Name:Plag1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:1891916. Plag1.

Subcellular locationi

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

GO - Cellular componenti

  1. nucleus Source: RefGenome
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 499499Zinc finger protein PLAG1PRO_0000295108Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki244 – 244Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki263 – 263Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

Post-translational modificationi

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).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).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Ubl conjugation

Proteomic databases

PRIDEiQ9QYE0.

PTM databases

PhosphoSiteiQ9QYE0.

Expressioni

Tissue specificityi

Expressed in heart, spleen, lung, kidney, brain, testis and epididymis but not in salivary glands.1 Publication

Developmental stagei

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.2 Publications

Gene expression databases

BgeeiQ9QYE0.
CleanExiMM_PLAG1.
ExpressionAtlasiQ9QYE0. baseline and differential.
GenevestigatoriQ9QYE0.

Interactioni

Subunit structurei

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).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ9QYE0.
SMRiQ9QYE0. Positions 32-239.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 8483Interacts with KPNA2By similarityAdd
BLAST
Regioni41 – 242202Decreased nuclear import with localization in the nucleus but also in the cytoplasmBy similarityAdd
BLAST
Regioni243 – 499257Activates transcription; Inhibition of nuclear import due to lack of NLS and KPNA2 interactionBy similarityAdd
BLAST
Regioni243 – 383141Repression domain; contains 3 sumoylation motifs and massively decrease transcription activityBy similarityAdd
BLAST
Regioni384 – 499116Massively activates transcriptionBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi22 – 254Nuclear localization signalBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi369 – 488120Ser-richAdd
BLAST

Domaini

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).By similarity

Sequence similaritiesi

Contains 7 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri34 – 5623C2H2-type 1PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri62 – 8625C2H2-type 2PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri92 – 11423C2H2-type 3PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri121 – 14323C2H2-type 4PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri150 – 17223C2H2-type 5PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri185 – 20723C2H2-type 6PROSITE-ProRule annotationAdd
BLAST
Zinc fingeri213 – 23624C2H2-type 7PROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG5048.
GeneTreeiENSGT00390000013640.
HOGENOMiHOG000294191.
HOVERGENiHBG053608.
InParanoidiQ9QYE0.
OMAiIDMDAVH.
OrthoDBiEOG71K62Q.
TreeFamiTF332024.

Family and domain databases

Gene3Di3.30.160.60. 5 hits.
InterProiIPR027775. C2H2_Znf_fam.
IPR027765. PLAG1.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PANTHERiPTHR10032. PTHR10032. 1 hit.
PTHR10032:SF124. PTHR10032:SF124. 1 hit.
PfamiPF00096. zf-C2H2. 1 hit.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 7 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 7 hits.
PS50157. ZINC_FINGER_C2H2_2. 7 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9QYE0-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MATVIPGDLS EVRDTQKAPS GKRKRGESKP RKNFPCQLCD KAFNSVEKLK
60 70 80 90 100
VHSFSHTGER PYKCTHQDCT KAFVSKYKLQ RHMATHSPEK THKCNYCEKM
110 120 130 140 150
FHRKDHLKNH LHTHDPNKET FKCEECGKSY NTKLGFKRHL ALHAATSGDL
160 170 180 190 200
TCKVCLQNFE STGVLLEHLK SHAGKSSGGV KEKKHQCEHC ERRFYTRKDV
210 220 230 240 250
RRHMVVHTGR KDFLCQYCAQ RFGRKDHLTR HMKKSHNQEL LKVKTEPVDF
260 270 280 290 300
LDPFTCNMSV PIKDELLPVM SLPSSELLSK PFTNTLQLNL YNTPFQSMQS
310 320 330 340 350
SGSAHQMITT LPLGMTCPID MDAVHPSHHL AFKCPFSSTS YAISIPEKEQ
360 370 380 390 400
PLKGEIESYL MELQGGAPSS SQDSPASSSK LGLEPQSGSP DDGAGDLSLS
410 420 430 440 450
KSSISISDPL STPALDFSQL FNFIPLNGPP YNPLSVGSLG MSYSQEEAHS
460 470 480 490
SVSQLPTQTQ DLQDPANTVG LSSLHSLSAA FTSSLSSSTT LPRFHQAFQ
Length:499
Mass (Da):55,579
Last modified:July 27, 2011 - v2
Checksum:iA3493D2DADCB83B2
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti433 – 4331P → T in AAS86161. (PubMed:15585652)Curated
Sequence conflicti433 – 4331P → T in AAF21762. 1 PublicationCurated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS17941.1.
RefSeqiNP_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.
UniGeneiMm.331467.

Genome annotation databases

EnsembliENSMUST00000003369; ENSMUSP00000003369; ENSMUSG00000003282.
GeneIDi56711.
KEGGimmu:56711.
UCSCiuc008rwp.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSi CCDS17941.1.
RefSeqi NP_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.
UniGenei Mm.331467.

3D structure databases

ProteinModelPortali Q9QYE0.
SMRi Q9QYE0. Positions 32-239.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei Q9QYE0.

Proteomic databases

PRIDEi Q9QYE0.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000003369 ; ENSMUSP00000003369 ; ENSMUSG00000003282 .
GeneIDi 56711.
KEGGi mmu:56711.
UCSCi uc008rwp.2. mouse.

Organism-specific databases

CTDi 5324.
MGIi MGI:1891916. Plag1.

Phylogenomic databases

eggNOGi COG5048.
GeneTreei ENSGT00390000013640.
HOGENOMi HOG000294191.
HOVERGENi HBG053608.
InParanoidi Q9QYE0.
OMAi IDMDAVH.
OrthoDBi EOG71K62Q.
TreeFami TF332024.

Miscellaneous databases

NextBioi 313179.
PROi Q9QYE0.
SOURCEi Search...

Gene expression databases

Bgeei Q9QYE0.
CleanExi MM_PLAG1.
ExpressionAtlasi Q9QYE0. baseline and differential.
Genevestigatori Q9QYE0.

Family and domain databases

Gene3Di 3.30.160.60. 5 hits.
InterProi IPR027775. C2H2_Znf_fam.
IPR027765. PLAG1.
IPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view ]
PANTHERi PTHR10032. PTHR10032. 1 hit.
PTHR10032:SF124. PTHR10032:SF124. 1 hit.
Pfami PF00096. zf-C2H2. 1 hit.
[Graphical view ]
SMARTi SM00355. ZnF_C2H2. 7 hits.
[Graphical view ]
PROSITEi PS00028. ZINC_FINGER_C2H2_1. 7 hits.
PS50157. ZINC_FINGER_C2H2_2. 7 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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. 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.

Entry informationi

Entry nameiPLAG1_MOUSE
AccessioniPrimary (citable) accession number: Q9QYE0
Secondary accession number(s): B1AXC4, Q3UXC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 10, 2007
Last sequence update: July 27, 2011
Last modified: October 29, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3