PA2G4_MOUSE
ID PA2G4_MOUSE Reviewed; 394 AA.
AC P50580;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Proliferation-associated protein 2G4;
DE AltName: Full=IRES-specific cellular trans-acting factor 45 kDa;
DE Short=ITAF45;
DE AltName: Full=Mpp1;
DE AltName: Full=Proliferation-associated protein 1;
DE AltName: Full=Protein p38-2G4;
GN Name=Pa2g4; Synonyms=Ebp1, Plfap;
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 [MRNA] (ISOFORM 2), INDUCTION, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=NFS;
RX PubMed=7556453; DOI=10.1006/excr.1995.1335;
RA Radomski N., Jost E.;
RT "Molecular cloning of a murine cDNA encoding a novel protein, p38-2G4,
RT which varies with the cell cycle.";
RL Exp. Cell Res. 220:434-445(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=NFS;
RX PubMed=9284967; DOI=10.18926/amo/30763;
RA Nakagawa Y., Watanabe S., Akiyama K., Sarker A.H., Tsutsui K., Inoue H.,
RA Seki S.;
RT "cDNA cloning, sequence analysis and expression of a mouse 44-kDa nuclear
RT protein copurified with DNA repair factors for acid-depurinated DNA.";
RL Acta Med. Okayama 51:195-206(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), RNA-BINDING, AND FUNCTION IN VIRAL
RP TRANSLATION.
RX PubMed=10950867;
RA Pilipenko E.V., Pestova T.V., Kolupaeva V.G., Khitrina E.V.,
RA Poperechnaya A.N., Agol V.I., Hellen C.U.;
RT "A cell cycle-dependent protein serves as a template-specific translation
RT initiation factor.";
RL Genes Dev. 14:2028-2045(2000).
RN [5]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15064750; DOI=10.1038/sj.onc.1207579;
RA Squatrito M., Mancino M., Donzelli M., Areces L.B., Draetta G.F.;
RT "EBP1 is a nucleolar growth-regulating protein that is part of pre-
RT ribosomal ribonucleoprotein complexes.";
RL Oncogene 23:4454-4465(2004).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 8-360, ABSENCE OF AMINOPEPTIDASE
RP ACTIVITY, FUNCTION, MUTAGENESIS OF 65-LYS--LYS-72, AND INTERACTION WITH
RP RNA.
RX PubMed=17690690; DOI=10.1038/sj.emboj.7601817;
RA Monie T.P., Perrin A.J., Birtley J.R., Sweeney T.R., Karakasiliotis I.,
RA Chaudhry Y., Roberts L.O., Matthews S., Goodfellow I.G., Curry S.;
RT "Structural insights into the transcriptional and translational roles of
RT Ebp1.";
RL EMBO J. 26:3936-3944(2007).
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 (By similarity).
CC Mediates cap-independent translation of specific viral IRESs (internal
CC ribosomal entry site). Together with PTBP1 is required for the
CC translation initiation on the foot-and-mouth disease virus (FMDV) IRES.
CC Regulates cell proliferation, differentiation, and survival. Isoform 1
CC suppresses apoptosis whereas isoform 2 promotes cell differentiation
CC (By similarity). {ECO:0000250|UniProtKB:Q6AYD3,
CC ECO:0000250|UniProtKB:Q9UQ80, ECO:0000269|PubMed:10950867,
CC ECO:0000269|PubMed:17690690}.
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 Interacts with AKT1 (By similarity). Isoform 1 and isoform 2 interact
CC with RNF20 (By similarity). Isoform 2 interacts with HUWE1. Interacts
CC with DNAJC21 (By similarity). {ECO:0000250|UniProtKB:Q6AYD3,
CC ECO:0000250|UniProtKB:Q9UQ80}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q9UQ80}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q9UQ80}. 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:7556453}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000305};
CC IsoId=P50580-1; Sequence=Displayed;
CC Name=2 {ECO:0000305};
CC IsoId=P50580-2; Sequence=VSP_057326;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:15064750}.
CC -!- DEVELOPMENTAL STAGE: Expressed in proliferating cells. Observed between
CC G1 and mid S phase, decrease toward the end of S phase, and disappear
CC at the S/G2 transition. {ECO:0000269|PubMed:15064750}.
CC -!- INDUCTION: By mitogens. {ECO:0000269|PubMed:7556453}.
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}.
CC -!- CAUTION: Although it belongs to the peptidase M24 family, it does not
CC contain metal cofactors and lacks aminopeptidase activity.
CC {ECO:0000305|PubMed:17690690}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X84789; CAA59260.1; -; mRNA.
DR EMBL; U43918; AAB60513.1; -; mRNA.
DR EMBL; BC046532; AAH46532.1; -; mRNA.
DR CCDS; CCDS24282.1; -. [P50580-1]
DR PIR; I48702; S54181.
DR RefSeq; NP_035249.1; NM_011119.3. [P50580-1]
DR PDB; 2V6C; X-ray; 2.50 A; A=9-360.
DR PDB; 6SWA; EM; 3.10 A; t=1-394.
DR PDBsum; 2V6C; -.
DR PDBsum; 6SWA; -.
DR AlphaFoldDB; P50580; -.
DR SMR; P50580; -.
DR BioGRID; 202246; 28.
DR IntAct; P50580; 3.
DR MINT; P50580; -.
DR STRING; 10090.ENSMUSP00000026425; -.
DR MEROPS; M24.978; -.
DR iPTMnet; P50580; -.
DR PhosphoSitePlus; P50580; -.
DR SwissPalm; P50580; -.
DR EPD; P50580; -.
DR jPOST; P50580; -.
DR PaxDb; P50580; -.
DR PeptideAtlas; P50580; -.
DR PRIDE; P50580; -.
DR ProteomicsDB; 295450; -. [P50580-1]
DR ProteomicsDB; 295451; -. [P50580-2]
DR DNASU; 18813; -.
DR Ensembl; ENSMUST00000026425; ENSMUSP00000026425; ENSMUSG00000025364. [P50580-1]
DR Ensembl; ENSMUST00000131728; ENSMUSP00000114434; ENSMUSG00000025364. [P50580-1]
DR GeneID; 18813; -.
DR KEGG; mmu:18813; -.
DR UCSC; uc007hnl.1; mouse. [P50580-1]
DR CTD; 5036; -.
DR MGI; MGI:894684; Pa2g4.
DR VEuPathDB; HostDB:ENSMUSG00000025364; -.
DR eggNOG; KOG2776; Eukaryota.
DR GeneTree; ENSGT00940000154281; -.
DR HOGENOM; CLU_041451_2_1_1; -.
DR InParanoid; P50580; -.
DR OMA; FPFAERW; -.
DR PhylomeDB; P50580; -.
DR TreeFam; TF300010; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 18813; 17 hits in 77 CRISPR screens.
DR ChiTaRS; Pa2g4; mouse.
DR EvolutionaryTrace; P50580; -.
DR PRO; PR:P50580; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P50580; protein.
DR Bgee; ENSMUSG00000025364; Expressed in embryonic post-anal tail and 251 other tissues.
DR ExpressionAtlas; P50580; baseline and differential.
DR Genevisible; P50580; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISO:MGI.
DR GO; GO:0003676; F:nucleic acid binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISS: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 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Ribonucleoprotein; RNA-binding; rRNA processing; Transcription;
KW Transcription regulation; 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_0000148990"
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:0000269|PubMed:17690690"
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:16452087"
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:0000305|PubMed:7556453"
FT /id="VSP_057326"
FT MUTAGEN 65..72
FT /note="KKEKEMKK->SSSSSSSS: No effect on RNA-binding."
FT /evidence="ECO:0000269|PubMed:17690690"
FT CONFLICT 279
FT /note="T -> A (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="K -> R (in Ref. 4; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT HELIX 15..36
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 45..60
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 72..82
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 105..114
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 117..126
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 138..156
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 163..176
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 186..189
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 198..204
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 223..233
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 260..272
FT /evidence="ECO:0007829|PDB:2V6C"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 286..298
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 301..305
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 316..326
FT /evidence="ECO:0007829|PDB:2V6C"
FT STRAND 329..332
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:2V6C"
FT HELIX 352..357
FT /evidence="ECO:0007829|PDB:2V6C"
SQ SEQUENCE 394 AA; 43699 MW; ABCD169F064261EB CRC64;
MSGEDEQQEQ TIAEDLVVTK YKMGGDIANR VLRSLVEASS SGVSVLSLCE KGDAMIMEET
GKIFKKEKEM KKGIAFPTSI SVNNCVCHFS PLKSDQDYIL KEGDLVKIDL GVHVDGFIAN
VAHTFVIGVA QGTQVTGRKA DVIKAAHLCA EAALRLVKPG NQNTQVTEAW NKVAHSFNCT
PIEGMLSHQL KQHVIDGEKT IIQNPTDQQK KDHEKAEFEV HEVYAVDVLV SSGEGKAKDA
GQRTTIYKRD PSKQYGLKMK TSRAFFSEVE RRFDAMPFTL RAFEDEKKAR MGVVECAKHE
LLQPFNVLYE KEGEFVAQFK FTVLLMPNGP MRITSGPFEP DLYKSEMEVQ DAELKALLQS
SASRKTQKKK KKKASKTVEN ATSGETLEEN GAGD
