PA2G4_RAT
ID PA2G4_RAT Reviewed; 394 AA.
AC Q6AYD3;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Proliferation-associated protein 2G4;
GN Name=Pa2g4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Li P.W., Adams M.D., Amanatides P.G., Baden-Tillson H.,
RA Barnstead M., Chin S.H., Dew I., Evans C.A., Ferriera S., Flanigan M.,
RA Fosler C., Glodek A., Gu Z., Holt R.A., Jennings D., Kraft C.L., Lu F.,
RA Nguyen T., Nusskern D.R., Pfannkoch C.M., Sitter C., Sutton G.G.,
RA Venter J.C., Wang Z., Woodage T., Zheng X.H., Zhong F.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [4]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION,
RP AND INTERACTION WITH AKT1.
RX PubMed=16832058; DOI=10.1073/pnas.0602923103;
RA Liu Z., Ahn J.Y., Liu X., Ye K.;
RT "Ebp1 isoforms distinctively regulate cell survival and differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10917-10922(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: May play a role in a ERBB3-regulated signal transduction
CC pathway. Seems be involved in growth regulation. Acts a corepressor of
CC the androgen receptor (AR) and is regulated by the ERBB3 ligand
CC neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-
CC regulated promoters, probably by recruiting histone acetylase (HAT)
CC activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs,
CC several rRNA precursors and probably U3 small nucleolar RNA. May be
CC involved in regulation of intermediate and late steps of rRNA
CC processing. May be involved in ribosome assembly. Mediates cap-
CC independent translation of specific viral IRESs (internal ribosomal
CC entry site). Together with PTBP1 is required for the translation
CC initiation on the foot-and-mouth disease virus (FMDV) IRES (By
CC similarity). Regulates cell proliferation, differentiation, and
CC survival. Isoform 1 suppresses apoptosis whereas isoform 2 promotes
CC cell differentiation. {ECO:0000250|UniProtKB:P50580,
CC ECO:0000250|UniProtKB:Q9UQ80, ECO:0000303|PubMed:16832058}.
CC -!- SUBUNIT: Isoform 2 interacts with the cytoplasmic domain of non-
CC phosphorylated ERBB3; the interaction requires PKC activity. Interacts
CC with AR. Treatment with HRG leads to dissociation from ERBB3 and
CC increases association with AR. Interacts with nucleolin/NCL. Component
CC of a ribonucleoprotein complex containing at least PA2G4, NCL, TOP1,
CC PABPC2, RPLP0, acetylated histone H1 (HIST1H1A or H1F1), histone H1
CC 2/4, RPL4, RPL8, RPL15, RPL18, RPL18A, RPL21, RPL11, RPL12, RPL28,
CC RPL27, RPLP2 and RPL24. Interacts with HDAC2. Interacts with RB1; the
CC interaction is enhanced upon PA2G4 dephosphorylation (By similarity).
CC Isoform 1 and isoform 2 interact with RNF20 (By similarity). Isoform 2
CC interacts with HUWE1 (By similarity). Interacts with AKT1. Interacts
CC with DNAJC21 (By similarity). {ECO:0000250|UniProtKB:Q9UQ80,
CC ECO:0000269|PubMed:16832058}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000269|PubMed:16832058}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:16832058}. Note=Phosphorylation at Ser-361 by
CC PKC/PRKCD regulates its nucleolar localization.
CC {ECO:0000250|UniProtKB:Q9UQ80}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:16832058}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000305}; Synonyms=p48 {ECO:0000269|PubMed:16832058};
CC IsoId=Q6AYD3-1; Sequence=Displayed;
CC Name=2 {ECO:0000305}; Synonyms=p42 {ECO:0000269|PubMed:16832058};
CC IsoId=Q6AYD3-2; Sequence=VSP_057324;
CC -!- PTM: Phosphorylated on serine and threonine residues. Phosphorylation
CC is enhanced by HRG treatment. Basal phosphorylation is PKC-dependent
CC and HRG-induced phosphorylation is predominantly PKC-independent.
CC Phosphorylation at Ser-361 by PKC/PRKCD regulates its nucleolar
CC localization. {ECO:0000250|UniProtKB:Q9UQ80}.
CC -!- PTM: Isoform 2 is polyubiquitinated, leading to proteasomal degradation
CC and phosphorylation by PKC/PRKCD enhances polyubiquitination.
CC {ECO:0000250|UniProtKB:Q9UQ80}.
CC -!- SIMILARITY: Belongs to the peptidase M24 family. {ECO:0000305}.
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DR EMBL; AABR06047173; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474104; EDL84836.1; -; Genomic_DNA.
DR EMBL; BC079095; AAH79095.1; -; mRNA.
DR RefSeq; NP_001004206.1; NM_001004206.1. [Q6AYD3-1]
DR AlphaFoldDB; Q6AYD3; -.
DR SMR; Q6AYD3; -.
DR IntAct; Q6AYD3; 3.
DR MINT; Q6AYD3; -.
DR STRING; 10116.ENSRNOP00000006578; -.
DR MEROPS; M24.978; -.
DR iPTMnet; Q6AYD3; -.
DR PhosphoSitePlus; Q6AYD3; -.
DR jPOST; Q6AYD3; -.
DR PaxDb; Q6AYD3; -.
DR PRIDE; Q6AYD3; -.
DR Ensembl; ENSRNOT00000096142; ENSRNOP00000091838; ENSRNOG00000004904. [Q6AYD3-1]
DR GeneID; 288778; -.
DR KEGG; rno:288778; -.
DR UCSC; RGD:1302994; rat. [Q6AYD3-1]
DR CTD; 5036; -.
DR RGD; 1302994; Pa2g4.
DR eggNOG; KOG2776; Eukaryota.
DR GeneTree; ENSGT00940000154281; -.
DR HOGENOM; CLU_041451_2_1_1; -.
DR InParanoid; Q6AYD3; -.
DR OMA; FPFAERW; -.
DR OrthoDB; 834026at2759; -.
DR PhylomeDB; Q6AYD3; -.
DR TreeFam; TF300010; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:Q6AYD3; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Proteomes; UP000234681; Chromosome 7.
DR Bgee; ENSRNOG00000004904; Expressed in thymus and 20 other tissues.
DR ExpressionAtlas; Q6AYD3; baseline and differential.
DR Genevisible; Q6AYD3; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0003676; F:nucleic acid binding; ISO:RGD.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IDA:UniProtKB.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.90.230.10; -; 1.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR004545; PA2G4.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR018349; Pept_M24A_MAP2_BS.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00557; Peptidase_M24; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR TIGRFAMs; TIGR00495; crvDNA_42K; 1.
DR PROSITE; PS01202; MAP_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Ribonucleoprotein;
KW RNA-binding; rRNA processing; Transcription; Transcription regulation;
KW Translation regulation; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT CHAIN 2..394
FT /note="Proliferation-associated protein 2G4"
FT /id="PRO_0000431530"
FT REGION 2..48
FT /note="Necessary for nucleolar localization"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT REGION 46..54
FT /note="RNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT REGION 301..394
FT /note="Necessary for nucleolar localization"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT REGION 358..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 361..375
FT /note="Interaction with RNA"
FT /evidence="ECO:0000250|UniProtKB:P50580"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT MOD_RES 361
FT /note="Phosphoserine; by PKC/PRKCD"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT MOD_RES 366
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT MOD_RES 386
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT CROSSLNK 298
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ80"
FT VAR_SEQ 1..54
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:16832058"
FT /id="VSP_057324"
SQ SEQUENCE 394 AA; 43657 MW; B3799DCF064371BB CRC64;
MSGEDEQQEQ TIAEDLVVTK YKMGGDIANR VLRSLVEASS SGVSVLSLCE KGDAMIMEET
GKIFKKEKEM KKGIAFPTSI SVNNCVCHFS PLKSDQDYIL KEGDLVKIDL GVHVDGFIAN
VAHTFVIGVA QGSQVTGRKA DVIKAAHLCA EAALRLVKPG NQNTQVTEAW NKVAHSFNCT
PIEGMLSHQL KQHVIDGEKT IIQNPTDQQK KDHEKAEFEV HEVYAVDVLV SSGEGKAKDA
GQRTTIYKRD PSKQYGLKMK TSRAFFSEVE RRFDAMPFTL RAFEDEKKAR MGVVECAKHE
LLQPFNVLYE KEGEFVAQFK FTVLLMPNGP MRITSGPFEP DLYKSEMEVQ DAELKALLQS
SASRKTQKKK KKKASKTAEN ATSGETLEEN GAGD
