PAGR1_HUMAN
ID PAGR1_HUMAN Reviewed; 254 AA.
AC Q9BTK6; A2ICR6;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=PAXIP1-associated glutamate-rich protein 1;
DE AltName: Full=Glutamate-rich coactivator interacting with SRC1 {ECO:0000303|PubMed:19039327};
DE Short=GAS {ECO:0000303|PubMed:19039327};
DE AltName: Full=PAXIP1-associated protein 1;
DE AltName: Full=PTIP-associated protein 1;
GN Name=PAGR1; Synonyms=C16orf53, PA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION BY MASS SPECTROMETRY, AND
RP IDENTIFICATION IN THE MLL2/3 COMPLEX.
RX PubMed=17500065; DOI=10.1074/jbc.m701574200;
RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T.,
RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.;
RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4
RT methyltransferase complex.";
RL J. Biol. Chem. 282:20395-20406(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [5]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP NCOA1 AND ESR1.
RX PubMed=19039327; DOI=10.1038/embor.2008.223;
RA Liang J., Zhang H., Zhang Y., Zhang Y., Shang Y.;
RT "GAS, a new glutamate-rich protein, interacts differentially with SRCs and
RT is involved in oestrogen receptor function.";
RL EMBO Rep. 10:51-57(2009).
RN [6]
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 [7]
RP FUNCTION, AND INTERACTION WITH NR3C1 AND AR.
RX PubMed=23161582; DOI=10.1074/jbc.m112.427740;
RA Zhang Z., Sun Y., Cho Y.W., Chow C.C., Simons S.S. Jr.;
RT "PA1 protein, a new competitive decelerator acting at more than one step to
RT impede glucocorticoid receptor-mediated transactivation.";
RL J. Biol. Chem. 288:42-58(2013).
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 (By similarity). 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 (By similarity). Involved in both estrogen receptor-regulated
CC gene transcription and estrogen-stimulated G1/S cell-cycle transition
CC (PubMed:19039327). 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 (PubMed:23161582).
CC {ECO:0000250|UniProtKB:Q99L02, ECO:0000269|PubMed:19039327,
CC ECO:0000269|PubMed:19124460, ECO:0000269|PubMed:23161582, ECO:0000305}.
CC -!- SUBUNIT: Component of the KMT2 family MLL2/MLL3 complex (also named
CC ASCOM complex), at least composed of the HMTs 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
CC (PubMed:17500065). Forms a constitutive complex with PAXIP1/PTIP
CC independently of the MLL2/MLL3 complex (By similarity). Interacts with
CC NCOA1, ESR1, NR3C1, AR (PubMed:19039327,PubMed:19124460,
CC PubMed:23161582). {ECO:0000250|UniProtKB:Q99L02,
CC ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:19039327,
CC ECO:0000269|PubMed:19124460, ECO:0000269|PubMed:23161582}.
CC -!- INTERACTION:
CC Q9BTK6; P03372: ESR1; NbExp=5; IntAct=EBI-2372223, EBI-78473;
CC Q9BTK6; Q15788: NCOA1; NbExp=4; IntAct=EBI-2372223, EBI-455189;
CC Q9BTK6; Q6ZW49: PAXIP1; NbExp=8; IntAct=EBI-2372223, EBI-743225;
CC Q9BTK6; P06536: Nr3c1; Xeno; NbExp=2; IntAct=EBI-2372223, EBI-1187143;
CC Q9BTK6; Q6NZQ4: Paxip1; Xeno; NbExp=5; IntAct=EBI-2372223, EBI-1395317;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19039327}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:19039327}.
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; EF195235; ABM69249.1; -; mRNA.
DR EMBL; AC009133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC120114; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471238; EAW79989.1; -; Genomic_DNA.
DR EMBL; BC003640; AAH03640.1; -; mRNA.
DR CCDS; CCDS10655.1; -.
DR RefSeq; NP_078792.1; NM_024516.3.
DR AlphaFoldDB; Q9BTK6; -.
DR BioGRID; 122672; 45.
DR ComplexPortal; CPX-7091; Histone-lysine N-methyltransferase complex, KMT2C variant.
DR ComplexPortal; CPX-7104; Histone-lysine N-methyltransferase complex, KMT2D variant.
DR CORUM; Q9BTK6; -.
DR IntAct; Q9BTK6; 34.
DR MINT; Q9BTK6; -.
DR STRING; 9606.ENSP00000326519; -.
DR iPTMnet; Q9BTK6; -.
DR PhosphoSitePlus; Q9BTK6; -.
DR BioMuta; PAGR1; -.
DR DMDM; 74733129; -.
DR EPD; Q9BTK6; -.
DR jPOST; Q9BTK6; -.
DR MassIVE; Q9BTK6; -.
DR MaxQB; Q9BTK6; -.
DR PaxDb; Q9BTK6; -.
DR PeptideAtlas; Q9BTK6; -.
DR PRIDE; Q9BTK6; -.
DR ProteomicsDB; 78994; -.
DR Antibodypedia; 75851; 75 antibodies from 21 providers.
DR DNASU; 79447; -.
DR Ensembl; ENST00000320330.8; ENSP00000326519.6; ENSG00000280789.2.
DR GeneID; 79447; -.
DR KEGG; hsa:79447; -.
DR MANE-Select; ENST00000320330.8; ENSP00000326519.6; NM_024516.4; NP_078792.1.
DR UCSC; uc002dug.5; human.
DR CTD; 79447; -.
DR DisGeNET; 79447; -.
DR GeneCards; PAGR1; -.
DR HGNC; HGNC:28707; PAGR1.
DR HPA; ENSG00000280789; Tissue enhanced (ovary).
DR MIM; 612033; gene.
DR neXtProt; NX_Q9BTK6; -.
DR OpenTargets; ENSG00000280789; -.
DR PharmGKB; PA142672260; -.
DR VEuPathDB; HostDB:ENSG00000280789; -.
DR eggNOG; ENOG502S0T8; Eukaryota.
DR GeneTree; ENSGT00390000016049; -.
DR HOGENOM; CLU_070349_0_0_1; -.
DR InParanoid; Q9BTK6; -.
DR OMA; QAWMPPP; -.
DR OrthoDB; 1630689at2759; -.
DR PhylomeDB; Q9BTK6; -.
DR TreeFam; TF326621; -.
DR PathwayCommons; Q9BTK6; -.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR SignaLink; Q9BTK6; -.
DR BioGRID-ORCS; 79447; 134 hits in 1077 CRISPR screens.
DR ChiTaRS; PAGR1; human.
DR GenomeRNAi; 79447; -.
DR Pharos; Q9BTK6; Tbio.
DR PRO; PR:Q9BTK6; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q9BTK6; protein.
DR Bgee; ENSG00000280789; Expressed in right hemisphere of cerebellum and 161 other tissues.
DR Genevisible; Q9BTK6; HS.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:MGI.
DR GO; GO:0044666; C:MLL3/4 complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0030331; F:nuclear estrogen receptor binding; IDA:UniProtKB.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
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; IMP:UniProtKB.
DR GO; GO:0033148; P:positive regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA: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..254
FT /note="PAXIP1-associated glutamate-rich protein 1"
FT /id="PRO_0000248334"
FT REGION 1..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 116..160
FT /note="Sufficient for interaction with NCOA1"
FT /evidence="ECO:0000269|PubMed:19039327"
FT REGION 127..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 161..254
FT /note="Sufficient for interaction with ESR1"
FT /evidence="ECO:0000269|PubMed:19039327"
FT COMPBIAS 47..65
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..92
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 157..227
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 138
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5M865"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5M865"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5M865"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5M865"
SQ SEQUENCE 254 AA; 27716 MW; 59E8231535CC12A6 CRC64;
MSLARGHGDT AASTAAPLSE EGEVTSGLQA LAVEDTGGPS ASAGKAEDEG EGGREETERE
GSGGEEAQGE VPSAGGEEPA EEDSEDWCVP CSDEEVELPA DGQPWMPPPS EIQRLYELLA
AHGTLELQAE ILPRRPPTPE AQSEEERSDE EPEAKEEEEE KPHMPTEFDF DDEPVTPKDS
LIDRRRTPGS SARSQKREAR LDKVLSDMKR HKKLEEQILR TGRDLFSLDS EDPSPASPPL
RSSGSSLFPR QRKY
