PGR1A_MOUSE
ID PGR1A_MOUSE Reviewed; 253 AA.
AC Q99L02;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=PAXIP1-associated glutamate-rich protein 1A {ECO:0000312|MGI:MGI:1914528};
DE AltName: Full=PAXIP1-associated protein 1;
DE AltName: Full=PTIP-associated protein 1;
GN Name=Pagr1a {ECO:0000312|MGI:MGI:1914528};
GN Synonyms=Pa1 {ECO:0000312|MGI:MGI:1914528}, Pagr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND INTERACTION WITH PAXIP1.
RX PubMed=19124460; DOI=10.1074/jbc.m809158200;
RA Gong Z., Cho Y.-W., Kim J.-E., Ge K., Chen J.;
RT "Accumulation of Pax2 transactivation domain interaction protein (PTIP) at
RT sites of DNA breaks via RNF8-dependent pathway is required for cell
RT survival after DNA damage.";
RL J. Biol. Chem. 284:7284-7293(2009).
RN [4]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, AND
RP FUNCTION.
RX PubMed=24633704; DOI=10.1002/dvdy.24125;
RA Kumar A., Lualdi M., Loncarek J., Cho Y.W., Lee J.E., Ge K., Kuehn M.R.;
RT "Loss of function of mouse Pax-Interacting Protein 1-associated glutamate
RT rich protein 1a (Pagr1a) leads to reduced Bmp2 expression and defects in
RT chorion and amnion development.";
RL Dev. Dyn. 243:937-947(2014).
RN [5]
RP FUNCTION, INTERACTION WITH PAXIP1, AND SUBCELLULAR LOCATION.
RX PubMed=26744420; DOI=10.1101/gad.268797.115;
RA Starnes L.M., Su D., Pikkupeura L.M., Weinert B.T., Santos M.A., Mund A.,
RA Soria R., Cho Y.W., Pozdnyakova I., Kubec Hoejfeldt M., Vala A., Yang W.,
RA Lopez-Mendez B., Lee J.E., Peng W., Yuan J., Ge K., Montoya G.,
RA Nussenzweig A., Choudhary C., Daniel J.A.;
RT "A PTIP-PA1 subcomplex promotes transcription for IgH class switching
RT independently from the associated MLL3/MLL4 methyltransferase complex.";
RL Genes Dev. 30:149-163(2016).
CC -!- FUNCTION: Its association with the histone methyltransferase MLL2/MLL3
CC complex is suggesting a role in epigenetic transcriptional activation.
CC However, in association with PAXIP1/PTIP is proposed to function at
CC least in part independently of the MLL2/MLL3 complex. Proposed to be
CC recruited by PAXIP1 to sites of DNA damage where the PAGR1:PAXIP1
CC complex is required for cell survival in response to DNA damage
CC independently of the MLL2/MLL3 complex (PubMed:19124460). However, its
CC function in DNA damage has been questioned (PubMed:26744420). During
CC immunoglobulin class switching in activated B-cells is involved in
CC transcription regulation of downstream switch regions at the
CC immunoglobulin heavy-chain (Igh) locus independently of the MLL2/MLL3
CC complex (PubMed:26744420). Involved in both estrogen receptor-regulated
CC gene transcription and estrogen-stimulated G1/S cell-cycle transition
CC (By similarity). Acts as transcriptional cofactor for nuclear hormone
CC receptors. Inhibits the induction properties of several steroid
CC receptors such as NR3C1, AR and PPARG; the mechanism of inhibition
CC appears to be gene-dependent (By similarity). May be involved in the
CC regulation of the BMP pathway in extraembryonic development
CC (PubMed:24633704). {ECO:0000250|UniProtKB:Q9BTK6,
CC ECO:0000269|PubMed:19124460, ECO:0000269|PubMed:26744420, ECO:0000305,
CC ECO:0000305|PubMed:24633704}.
CC -!- SUBUNIT: Component of the KMT2 family MLL2/MLL3 complex, at least
CC composed of the histone methyltransferases KMT2D and/or KMT2C, the
CC common subunits ASH2L, RBBP5, WDR5 and DPY30, and the complex type-
CC specific subunits PAXIP1/PTIP, PAGR1, NCOA6 and KDM6A; PAXIP1 is
CC required for the association with the MLL2/MLL3 complex (By
CC similarity). Forms a constitutive complex with PAXIP1/PTIP
CC independently of the MLL2/MLL3 complex (PubMed:19124460,
CC PubMed:26744420). Interacts with NCOA1, ESR1, NR3C1, AR (By
CC similarity). {ECO:0000250|UniProtKB:Q9BTK6,
CC ECO:0000269|PubMed:19124460, ECO:0000269|PubMed:26744420}.
CC -!- INTERACTION:
CC Q99L02; Q6NZQ4: Paxip1; NbExp=11; IntAct=EBI-11667455, EBI-1395317;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26744420}.
CC -!- DEVELOPMENTAL STAGE: Expression first detected at 5.0-6.0 dpc in the
CC extraembryonic region, at 7.5 dpc detected within the chorion; later
CC the expression is expanding to the entire embryo.
CC {ECO:0000269|PubMed:24633704}.
CC -!- DISRUPTION PHENOTYPE: Normal germ layer specification and developmental
CC patterning but limited anterior development and arrest by 8.5 dpc,
CC likely due at least in part to defects in extraembryonic tissue.
CC {ECO:0000269|PubMed:24633704}.
CC -!- CAUTION: The terminology of MLL proteins in mammalia is not consistent
CC also concerning the terminology of MLL protein-containing complexes.
CC The decribed MLL2/MLL3 complex is commonly described as MLL3/MLL4
CC complex in literature. {ECO:0000305}.
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DR EMBL; AK082775; BAC38614.1; -; mRNA.
DR EMBL; BC003932; AAH03932.1; -; mRNA.
DR CCDS; CCDS21854.1; -.
DR RefSeq; NP_084516.1; NM_030240.1.
DR AlphaFoldDB; Q99L02; -.
DR BioGRID; 212067; 3.
DR IntAct; Q99L02; 1.
DR STRING; 10090.ENSMUSP00000032918; -.
DR iPTMnet; Q99L02; -.
DR PhosphoSitePlus; Q99L02; -.
DR EPD; Q99L02; -.
DR jPOST; Q99L02; -.
DR MaxQB; Q99L02; -.
DR PaxDb; Q99L02; -.
DR PeptideAtlas; Q99L02; -.
DR PRIDE; Q99L02; -.
DR DNASU; 67278; -.
DR Ensembl; ENSMUST00000200948; ENSMUSP00000144469; ENSMUSG00000030680.
DR Ensembl; ENSMUST00000202798; ENSMUSP00000144243; ENSMUSG00000107068.
DR GeneID; 67278; -.
DR KEGG; mmu:67278; -.
DR UCSC; uc009jtx.1; mouse.
DR CTD; 67278; -.
DR MGI; MGI:1914528; Pagr1a.
DR VEuPathDB; HostDB:ENSMUSG00000030680; -.
DR VEuPathDB; HostDB:ENSMUSG00000107068; -.
DR eggNOG; ENOG502S0T8; Eukaryota.
DR GeneTree; ENSGT00390000016049; -.
DR HOGENOM; CLU_088613_1_0_1; -.
DR InParanoid; Q99L02; -.
DR OMA; QAWMPPP; -.
DR OrthoDB; 1630689at2759; -.
DR PhylomeDB; Q99L02; -.
DR TreeFam; TF326621; -.
DR BioGRID-ORCS; 67278; 8 hits in 77 CRISPR screens.
DR ChiTaRS; Pagr1a; mouse.
DR PRO; PR:Q99L02; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q99L02; protein.
DR Bgee; ENSMUSG00000030680; Expressed in cerebellar cortex and 63 other tissues.
DR ExpressionAtlas; Q99L02; baseline and differential.
DR Genevisible; Q99L02; MM.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:MGI.
DR GO; GO:0044666; C:MLL3/4 complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISO:MGI.
DR GO; GO:0060717; P:chorion development; IMP:MGI.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0071557; P:histone H3-K27 demethylation; IDA:MGI.
DR GO; GO:0051568; P:histone H3-K4 methylation; IBA:GO_Central.
DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; ISO:MGI.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; ISO:MGI.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IMP:UniProtKB.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:1902749; P:regulation of cell cycle G2/M phase transition; IMP:UniProtKB.
DR InterPro; IPR028213; PA1.
DR PANTHER; PTHR28467; PTHR28467; 1.
DR Pfam; PF15364; PAXIP1_C; 1.
PE 1: Evidence at protein level;
KW DNA damage; DNA recombination; DNA repair; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..253
FT /note="PAXIP1-associated glutamate-rich protein 1A"
FT /evidence="ECO:0000305"
FT /id="PRO_0000248335"
FT REGION 1..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..159
FT /note="Sufficient for interaction with NCOA1"
FT /evidence="ECO:0000250|UniProtKB:Q9BTK6"
FT REGION 126..253
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 160..253
FT /note="Sufficient for interaction with ESR1"
FT /evidence="ECO:0000250|UniProtKB:Q9BTK6"
FT COMPBIAS 48..85
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..221
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 229..253
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 137
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5M865"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5M865"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5M865"
FT MOD_RES 236
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5M865"
SQ SEQUENCE 253 AA; 27723 MW; AA5E4C4503A5C6FF CRC64;
MSLALGHGTI AGSTAAPLSE EGEVTSGLQA LAVEDTGGPS VSASKAEEEG KGSQEEAGRE
GSRPEEALEA PSAASDERAE GEAEDWCVPC SDEEVELPAN GQSWMPPPSE IQRLYELLAT
QGTLELQAEI LPRRPPTPEA QSEEERSDEE PEAKEEEEEK PHMPTEFDFD DEPMTPKDSL
IDRRRTPGSS ARSQKREARL DKVLSDMKRH KKLEEQILRT GRDLFSLDSE GPSPTSPPLR
SSGNSLFPRQ RKY
