PNRC2_HUMAN
ID PNRC2_HUMAN Reviewed; 139 AA.
AC Q9NPJ4; B4DU72;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Proline-rich nuclear receptor coactivator 2;
GN Name=PNRC2; ORFNames=HSPC208;
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 [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP DOMAIN, MUTAGENESIS OF PRO-101 AND PRO-104, AND INTERACTION WITH ESR1;
RP ESRRA; NR3C1; NR5A1; PGR; TR; RAR AND RXR.
RX PubMed=11574675; DOI=10.1093/nar/29.19.3939;
RA Zhou D., Chen S.;
RT "PNRC2 is a 16 kDa coactivator that interacts with nuclear receptors
RT through an SH3-binding motif.";
RL Nucleic Acids Res. 29:3939-3948(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Prostate;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, Ovary, and Uterus;
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 [6]
RP INTERACTION WITH ESRRG.
RX PubMed=14651967; DOI=10.1016/j.bbrc.2003.11.025;
RA Hentschke M., Borgmeyer U.;
RT "Identification of PNRC2 and TLE1 as activation function-1 cofactors of the
RT orphan nuclear receptor ERRgamma.";
RL Biochem. Biophys. Res. Commun. 312:975-982(2003).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH UPF1 AND DCP1A.
RX PubMed=19150429; DOI=10.1016/j.molcel.2008.11.022;
RA Cho H., Kim K.M., Kim Y.K.;
RT "Human proline-rich nuclear receptor coregulatory protein 2 mediates an
RT interaction between mRNA surveillance machinery and decapping complex.";
RL Mol. Cell 33:75-86(2009).
RN [8]
RP FUNCTION, INTERACTION WITH NR3C1; UPF1 AND DCP1A, AND MUTAGENESIS OF
RP PRO-101; PRO-104; PRO-108 AND TRP-114.
RX PubMed=25775514; DOI=10.1073/pnas.1409612112;
RA Cho H., Park O.H., Park J., Ryu I., Kim J., Ko J., Kim Y.K.;
RT "Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner
RT to recruit UPF1 for rapid mRNA degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:E1540-E1549(2015).
CC -!- FUNCTION: Involved in nonsense-mediated mRNA decay (NMD) by acting as a
CC bridge between the mRNA decapping complex and the NMD machinery
CC (PubMed:19150429). May act by targeting the NMD machinery to the P-body
CC and recruiting the decapping machinery to aberrant mRNAs
CC (PubMed:19150429). Required for UPF1/RENT1 localization to the P-body
CC (PubMed:19150429). Plays a role in glucocorticoid receptor-mediated
CC mRNA degradation by interacting with the glucocorticoid receptor NR3C1
CC in a ligand-dependent manner when it is bound to the 5' UTR of target
CC mRNAs and recruiting the RNA helicase UPF1 and the mRNA-decapping
CC enzyme DCP1A, leading to RNA decay (PubMed:25775514). Also acts as a
CC nuclear receptor coactivator (PubMed:11574675). May play a role in
CC controlling the energy balance between energy storage and energy
CC expenditure (By similarity). {ECO:0000250|UniProtKB:Q9CR73,
CC ECO:0000269|PubMed:11574675, ECO:0000269|PubMed:19150429,
CC ECO:0000269|PubMed:25775514}.
CC -!- SUBUNIT: Interacts with UPF1/RENT1; preferentially interacts with
CC hyperphosphorylated form (PubMed:19150429, PubMed:25775514). Interacts
CC with DCP1A (PubMed:19150429, PubMed:25775514). Interacts with many
CC nuclear receptors including ESR1, ESRRA, ESRRG, NR3C1/GR, NR5A1, PGR,
CC TR, RAR and RXR (PubMed:11574675, PubMed:14651967, PubMed:25775514).
CC {ECO:0000269|PubMed:11574675, ECO:0000269|PubMed:14651967,
CC ECO:0000269|PubMed:19150429, ECO:0000269|PubMed:25775514}.
CC -!- INTERACTION:
CC Q9NPJ4; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-726549, EBI-11524452;
CC Q9NPJ4; Q9NPI6: DCP1A; NbExp=11; IntAct=EBI-726549, EBI-374238;
CC Q9NPJ4; P62508-3: ESRRG; NbExp=3; IntAct=EBI-726549, EBI-12001340;
CC Q9NPJ4; P51570: GALK1; NbExp=3; IntAct=EBI-726549, EBI-2269932;
CC Q9NPJ4; Q92900: UPF1; NbExp=9; IntAct=EBI-726549, EBI-373471;
CC Q9NPJ4-1; Q9NPI6: DCP1A; NbExp=6; IntAct=EBI-16018718, EBI-374238;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19150429}. Cytoplasm,
CC P-body {ECO:0000269|PubMed:19150429}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NPJ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NPJ4-2; Sequence=VSP_037463;
CC -!- TISSUE SPECIFICITY: Expressed in heart, lung, muscle and brain.
CC {ECO:0000269|PubMed:11574675}.
CC -!- DOMAIN: The interaction between PNRC2 and nuclear receptors is
CC dependent on the SH3 binding motif. {ECO:0000269|PubMed:11574675}.
CC -!- SIMILARITY: Belongs to the PNRC family. PNRC2 subfamily. {ECO:0000305}.
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DR EMBL; AF374386; AAK54613.1; -; mRNA.
DR EMBL; AF151042; AAF36128.1; -; mRNA.
DR EMBL; AK000319; BAA91082.1; -; mRNA.
DR EMBL; AK300522; BAG62234.1; -; mRNA.
DR EMBL; AL590609; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001959; AAH01959.1; -; mRNA.
DR EMBL; BC078177; AAH78177.1; -; mRNA.
DR EMBL; BC085018; AAH85018.1; -; mRNA.
DR CCDS; CCDS246.1; -. [Q9NPJ4-1]
DR RefSeq; NP_060231.1; NM_017761.3. [Q9NPJ4-1]
DR RefSeq; XP_016857180.1; XM_017001691.1. [Q9NPJ4-1]
DR PDB; 4B6H; X-ray; 2.60 A; C/D=1-121.
DR PDB; 5KQ1; X-ray; 3.00 A; C/F=91-121.
DR PDB; 5KQ4; X-ray; 2.56 A; C/F=91-121.
DR PDBsum; 4B6H; -.
DR PDBsum; 5KQ1; -.
DR PDBsum; 5KQ4; -.
DR AlphaFoldDB; Q9NPJ4; -.
DR SMR; Q9NPJ4; -.
DR BioGRID; 120768; 31.
DR CORUM; Q9NPJ4; -.
DR DIP; DIP-41328N; -.
DR IntAct; Q9NPJ4; 18.
DR MINT; Q9NPJ4; -.
DR STRING; 9606.ENSP00000334840; -.
DR iPTMnet; Q9NPJ4; -.
DR PhosphoSitePlus; Q9NPJ4; -.
DR BioMuta; PNRC2; -.
DR EPD; Q9NPJ4; -.
DR MassIVE; Q9NPJ4; -.
DR MaxQB; Q9NPJ4; -.
DR PaxDb; Q9NPJ4; -.
DR PeptideAtlas; Q9NPJ4; -.
DR PRIDE; Q9NPJ4; -.
DR ProteomicsDB; 82026; -. [Q9NPJ4-1]
DR ProteomicsDB; 82027; -. [Q9NPJ4-2]
DR Antibodypedia; 49958; 109 antibodies from 19 providers.
DR DNASU; 55629; -.
DR Ensembl; ENST00000334351.8; ENSP00000334840.7; ENSG00000189266.13. [Q9NPJ4-1]
DR Ensembl; ENST00000374468.1; ENSP00000363592.1; ENSG00000189266.13. [Q9NPJ4-1]
DR Ensembl; ENST00000647887.1; ENSP00000497590.1; ENSG00000189266.13. [Q9NPJ4-1]
DR GeneID; 55629; -.
DR KEGG; hsa:55629; -.
DR MANE-Select; ENST00000334351.8; ENSP00000334840.7; NM_017761.4; NP_060231.1.
DR UCSC; uc001big.4; human. [Q9NPJ4-1]
DR CTD; 55629; -.
DR DisGeNET; 55629; -.
DR GeneCards; PNRC2; -.
DR HGNC; HGNC:23158; PNRC2.
DR HPA; ENSG00000189266; Low tissue specificity.
DR MIM; 611882; gene.
DR neXtProt; NX_Q9NPJ4; -.
DR OpenTargets; ENSG00000189266; -.
DR PharmGKB; PA134931421; -.
DR VEuPathDB; HostDB:ENSG00000189266; -.
DR eggNOG; ENOG502RZZX; Eukaryota.
DR GeneTree; ENSGT00530000063881; -.
DR HOGENOM; CLU_086541_1_0_1; -.
DR InParanoid; Q9NPJ4; -.
DR OMA; KERGHGC; -.
DR PhylomeDB; Q9NPJ4; -.
DR TreeFam; TF333211; -.
DR PathwayCommons; Q9NPJ4; -.
DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR SignaLink; Q9NPJ4; -.
DR BioGRID-ORCS; 55629; 31 hits in 1038 CRISPR screens.
DR ChiTaRS; PNRC2; human.
DR GeneWiki; PNRC2; -.
DR GenomeRNAi; 55629; -.
DR Pharos; Q9NPJ4; Tbio.
DR PRO; PR:Q9NPJ4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NPJ4; protein.
DR Bgee; ENSG00000189266; Expressed in germinal epithelium of ovary and 204 other tissues.
DR ExpressionAtlas; Q9NPJ4; baseline and differential.
DR Genevisible; Q9NPJ4; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0031087; P:deadenylation-independent decapping of nuclear-transcribed mRNA; TAS:UniProtKB.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IDA:UniProtKB.
DR InterPro; IPR026780; PNRC1/2.
DR InterPro; IPR026781; PNRC2.
DR PANTHER; PTHR15405; PTHR15405; 1.
DR PANTHER; PTHR15405:SF6; PTHR15405:SF6; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Cytoplasm;
KW Nonsense-mediated mRNA decay; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..139
FT /note="Proline-rich nuclear receptor coactivator 2"
FT /id="PRO_0000058485"
FT REGION 1..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 99..105
FT /note="SH3-binding"
FT COMPBIAS 11..32
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..54
FT /note="MGGGERYNIPAPQSRNVSKNQQQLNRQKTKEQNSQMKIVHKKKERGHGYNSS
FT AA -> MLASAPRLNSADRPMKTSVLRQRKGSVRKQHLLSW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037463"
FT MUTAGEN 101
FT /note="P->A: Abolishes the interaction with the nuclear
FT receptors but not decapping enzyme; when associated with A-
FT 104."
FT /evidence="ECO:0000269|PubMed:11574675,
FT ECO:0000269|PubMed:25775514"
FT MUTAGEN 104
FT /note="P->A: Abolishes the interaction with the nuclear
FT receptors but not decapping enzyme; when associated with A-
FT 101."
FT /evidence="ECO:0000269|PubMed:11574675,
FT ECO:0000269|PubMed:25775514"
FT MUTAGEN 108
FT /note="P->A: Abolishes the interaction with DCP1A."
FT /evidence="ECO:0000269|PubMed:25775514"
FT MUTAGEN 114
FT /note="W->A: Abolishes the interaction with DCP1A."
FT /evidence="ECO:0000269|PubMed:25775514"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:5KQ4"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:5KQ4"
SQ SEQUENCE 139 AA; 15591 MW; 072039CB52551F90 CRC64;
MGGGERYNIP APQSRNVSKN QQQLNRQKTK EQNSQMKIVH KKKERGHGYN SSAAAWQAMQ
NGGKNKNFPN NQSWNSSLSG PRLLFKSQAN QNYAGAKFSE PPSPSVLPKP PSHWVPVSFN
PSDKEIMTFQ LKTLLKVQV
