Full text data of PA2G4
PA2G4
(EBP1)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog; hG4-1; ErbB3-binding protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog; hG4-1; ErbB3-binding protein 1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UQ80
ID PA2G4_HUMAN Reviewed; 394 AA.
AC Q9UQ80; O43846; Q9UM59;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Proliferation-associated protein 2G4;
DE AltName: Full=Cell cycle protein p38-2G4 homolog;
DE Short=hG4-1;
DE AltName: Full=ErbB3-binding protein 1;
GN Name=PA2G4; Synonyms=EBP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9345902;
RA Lamartine J., Seri M., Cinti R., Heitzmann F., Creaven M.,
RA Radomski N., Jost E., Lenoir G.M., Romeo G., Sylla B.S.;
RT "Molecular cloning and mapping of a human cDNA (PA2G4) that encodes a
RT protein highly homologous to the mouse cell cycle protein p38-2G4.";
RL Cytogenet. Cell Genet. 78:31-35(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH ERBB3, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=10682683; DOI=10.1054/bjoc.1999.0981;
RA Yoo J.Y., Wang X.W., Rishi A.K., Lessor T., Xia X.M., Gustafson T.A.,
RA Hamburger A.W.;
RT "Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of
RT this binding by heregulin.";
RL Br. J. Cancer 82:683-690(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Caroli F., Lamartine J., Sylla B.S., Romeo G., Seri M.;
RT "Genomic structure of the human PA2G4 gene.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-20; 23-30; 34-62; 73-101; 156-172; 200-211;
RP 216-236; 264-281 AND 299-364, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma, Mammary carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Matallanas D., Cooper W.N., Boldt K.,
RA von Kriegsheim A.F., Kolch W.;
RL Submitted (JAN-2010) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 34-51; 216-236; 264-271; 299-311; 333-344 AND
RP 377-394, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP INTERACTION WITH ERBB3, PHOSPHORYLATION, PHOSPHORYLATION BY PKC,
RP PHOSPHORYLATION AT THR-366, AND MUTAGENESIS OF SER-363 AND THR-366.
RX PubMed=11325528; DOI=10.1016/S0303-7207(01)00387-2;
RA Lessor T.J., Hamburger A.W.;
RT "Regulation of the ErbB3 binding protein Ebp1 by protein kinase C.";
RL Mol. Cell. Endocrinol. 175:185-191(2001).
RN [8]
RP FUNCTION IN TRANSCRIPTION REPRESSION, AND INTERACTION WITH RB1.
RX PubMed=11268000; DOI=10.1002/jcp.1075;
RA Xia X., Cheng A., Lessor T., Zhang Y., Hamburger A.W.;
RT "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb
RT transcriptional regulation.";
RL J. Cell. Physiol. 187:209-217(2001).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE
RP SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.E02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [10]
RP FUNCTION IN E2F1-MEDIATED TRANSCRIPTION REPRESSION, AND INTERACTION
RP WITH HDAC2.
RX PubMed=12682367; DOI=10.1093/nar/gkg318;
RA Zhang Y., Woodford N., Xia X., Hamburger A.W.;
RT "Repression of E2F1-mediated transcription by the ErbB3 binding
RT protein Ebp1 involves histone deacetylases.";
RL Nucleic Acids Res. 31:2168-2177(2003).
RN [11]
RP FUNCTION IN RRNA PROCESSING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP RNA-BINDING, IDENTIFICATION IN A RIBONUCLEOPROTEIN COMPLEX,
RP ASSOCIATION WITH RRNA, ASSOCIATION WITH U3 SNORNA, AND MUTAGENESIS OF
RP 20-LYS--LYS-22 AND 364-ARG-LYS-365.
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 [12]
RP FUNCTION IN TRANSCRIPTION REPRESSION, AND INTERACTION WITH ERBB3 AND
RP AR.
RX PubMed=15583694; DOI=10.1038/sj.bjc.6602257;
RA Zhang Y., Hamburger A.W.;
RT "Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein
RT 1) mediated repression of androgen receptor signalling.";
RL Br. J. Cancer 92:140-146(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND THR-386, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-386, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361 AND THR-386, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-386, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2; SER-361 AND THR-386, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2 AND THR-386, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), INTERACTION WITH 5S RIBOSOMAL
RP RNA, LACK OF METAL COFACTOR, AND LACK OF AMINOPEPTIDASE ACTIVITY.
RX PubMed=17765895; DOI=10.1016/j.febslet.2007.08.024;
RA Kowalinski E., Bange G., Bradatsch B., Hurt E., Wild K., Sinning I.;
RT "The crystal structure of Ebp1 reveals a methionine aminopeptidase
RT fold as binding platform for multiple interactions.";
RL FEBS Lett. 581:4450-4454(2007).
CC -!- FUNCTION: May play a role in a ERBB3-regulated signal transduction
CC pathway. Seems be involved in growth regulation. Acts a
CC corepressor of the androgen receptor (AR) and is regulated by the
CC ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription
CC of some E2F1-regulated promoters, probably by recruiting histone
CC acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and
CC 5.8S mature rRNAs, several rRNA precursors and probably U3 small
CC nucleolar RNA. May be involved in regulation of intermediate and
CC late steps of rRNA processing. May be involved in ribosome
CC assembly. Mediates cap-independent translation of specific viral
CC IRESs (internal ribosomal entry site) (By similarity).
CC -!- SUBUNIT: Interacts with the cytoplasmic domain of non-
CC phosphorylated ERBB3; the interaction requires PKC activity.
CC Interacts with AR. Treatment with HRG leads to dissociation from
CC ERBB3 and increases association with AR. Interacts with
CC NCL/nucleolin. Component of a ribonucleoprotein complex containing
CC at least PA2G4, NCL, TOP1, PABPC2, RPLP0, acetylated histone H1
CC (HIST1H1A or H1F1), histone H1 2/4, RPL4, RPL8, RPL15, RPL18,
CC RPL18A, RPL21, RPL11, RPL12, RPL28, RPL27, RPLP2 and RPL24.
CC Interacts with HDAC2. Interacts with RB1; the interaction is
CC enhanced upon PA2G4 dephosphorylation.
CC -!- INTERACTION:
CC P19338:NCL; NbExp=2; IntAct=EBI-924893, EBI-346967;
CC P06400:RB1; NbExp=4; IntAct=EBI-924893, EBI-491274;
CC Q96ST3:SIN3A; NbExp=4; IntAct=EBI-924893, EBI-347218;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus.
CC Note=Tranlocates to the nucleus upon treatment with HRG.
CC -!- TISSUE SPECIFICITY: Expressed in several cell lines tested,
CC including primary and transformed cell lines.
CC -!- PTM: Phosphorylated on serine and threonine residues.
CC Phosphorylation is enhanced by HRG treatment. Basal
CC phosphorylation is PKC-dependent and HRG-induced phosphorylation
CC is predominantly PKC-independent.
CC -!- SIMILARITY: Belongs to the peptidase M24 family.
CC -!- CAUTION: Although it belongs to the peptidase M24 family, it does
CC not contain metal cofactors and lacks aminopeptidase activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD00646.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PA2G4ID41628ch12q13.html";
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DR EMBL; U59435; AAB91536.1; -; mRNA.
DR EMBL; U87954; AAD00646.1; ALT_INIT; mRNA.
DR EMBL; AF104670; AAD05561.1; -; Genomic_DNA.
DR EMBL; AF104668; AAD05561.1; JOINED; Genomic_DNA.
DR EMBL; AF104669; AAD05561.1; JOINED; Genomic_DNA.
DR EMBL; BC001951; AAH01951.1; -; mRNA.
DR EMBL; BC007561; AAH07561.1; -; mRNA.
DR EMBL; BC069786; AAH69786.1; -; mRNA.
DR RefSeq; NP_006182.2; NM_006191.2.
DR UniGene; Hs.524498; -.
DR UniGene; Hs.745109; -.
DR PDB; 2Q8K; X-ray; 1.60 A; A=2-394.
DR PDB; 3J2I; EM; 11.90 A; A=1-394.
DR PDBsum; 2Q8K; -.
DR PDBsum; 3J2I; -.
DR ProteinModelPortal; Q9UQ80; -.
DR SMR; Q9UQ80; 7-362.
DR IntAct; Q9UQ80; 43.
DR MINT; MINT-5000754; -.
DR STRING; 9606.ENSP00000302886; -.
DR MEROPS; M24.973; -.
DR PhosphoSite; Q9UQ80; -.
DR DMDM; 13632817; -.
DR SWISS-2DPAGE; Q9UQ80; -.
DR PaxDb; Q9UQ80; -.
DR PRIDE; Q9UQ80; -.
DR DNASU; 5036; -.
DR Ensembl; ENST00000303305; ENSP00000302886; ENSG00000170515.
DR GeneID; 5036; -.
DR KEGG; hsa:5036; -.
DR UCSC; uc001sjm.3; human.
DR CTD; 5036; -.
DR GeneCards; GC12P056498; -.
DR HGNC; HGNC:8550; PA2G4.
DR HPA; CAB011711; -.
DR HPA; CAB012428; -.
DR HPA; HPA016484; -.
DR MIM; 602145; gene.
DR neXtProt; NX_Q9UQ80; -.
DR PharmGKB; PA32877; -.
DR eggNOG; COG0024; -.
DR HOGENOM; HOG000168207; -.
DR HOVERGEN; HBG053117; -.
DR InParanoid; Q9UQ80; -.
DR OMA; VWYKPEL; -.
DR OrthoDB; EOG7SFHXD; -.
DR PhylomeDB; Q9UQ80; -.
DR EvolutionaryTrace; Q9UQ80; -.
DR GeneWiki; PA2G4; -.
DR GenomeRNAi; 5036; -.
DR NextBio; 19404; -.
DR PRO; PR:Q9UQ80; -.
DR ArrayExpress; Q9UQ80; -.
DR Bgee; Q9UQ80; -.
DR CleanEx; HS_PA2G4; -.
DR Genevestigator; Q9UQ80; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:MGI.
DR GO; GO:0007050; P:cell cycle arrest; TAS:ProtInc.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:MGI.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.90.230.10; -; 2.
DR InterPro; IPR004545; Pap_1.
DR InterPro; IPR000994; Pept_M24_structural-domain.
DR InterPro; IPR018349; Pept_M24A_MAP2_BS.
DR InterPro; IPR011991; WHTH_DNA-bd_dom.
DR Pfam; PF00557; Peptidase_M24; 1.
DR SUPFAM; SSF55920; SSF55920; 2.
DR TIGRFAMs; TIGR00495; crvDNA_42K; 1.
DR PROSITE; PS01202; MAP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Ribonucleoprotein; RNA-binding;
KW rRNA processing; Transcription; Transcription regulation;
KW Translation regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 394 Proliferation-associated protein 2G4.
FT /FTId=PRO_0000148989.
FT REGION 2 48 Necessary for nucleolar localization.
FT REGION 46 54 RNA-binding.
FT REGION 301 394 Necessary for nucleolar localization.
FT REGION 361 375 Interaction with RNA (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 361 361 Phosphoserine.
FT MOD_RES 366 366 Phosphothreonine (Probable).
FT MOD_RES 386 386 Phosphothreonine.
FT MUTAGEN 20 22 KYK->AYA: Loss of nucleolar localization.
FT MUTAGEN 363 363 S->A: No effect on in vitro
FT phosphorylation by PKC.
FT MUTAGEN 364 365 RK->AA: Only partial nucleolar
FT localization.
FT MUTAGEN 366 366 T->A: Decreases in vitro phosphorylation
FT by PKC.
FT CONFLICT 381 381 A -> P (in Ref. 1; AAB91536).
FT HELIX 15 38
FT HELIX 45 61
FT STRAND 72 82
FT STRAND 85 87
FT STRAND 105 114
FT STRAND 117 126
FT HELIX 137 156
FT HELIX 163 175
FT TURN 176 178
FT STRAND 186 191
FT STRAND 194 196
FT STRAND 200 204
FT HELIX 207 212
FT STRAND 223 233
FT STRAND 246 249
FT HELIX 260 273
FT HELIX 280 282
FT HELIX 287 298
FT STRAND 301 305
FT STRAND 316 326
FT STRAND 329 332
FT HELIX 340 342
FT HELIX 352 359
SQ SEQUENCE 394 AA; 43787 MW; CD45466507AD6047 CRC64;
MSGEDEQQEQ TIAEDLVVTK YKMGGDIANR VLRSLVEASS SGVSVLSLCE KGDAMIMEET
GKIFKKEKEM KKGIAFPTSI SVNNCVCHFS PLKSDQDYIL KEGDLVKIDL GVHVDGFIAN
VAHTFVVDVA QGTQVTGRKA 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 EAGD
//
ID PA2G4_HUMAN Reviewed; 394 AA.
AC Q9UQ80; O43846; Q9UM59;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 139.
DE RecName: Full=Proliferation-associated protein 2G4;
DE AltName: Full=Cell cycle protein p38-2G4 homolog;
DE Short=hG4-1;
DE AltName: Full=ErbB3-binding protein 1;
GN Name=PA2G4; Synonyms=EBP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9345902;
RA Lamartine J., Seri M., Cinti R., Heitzmann F., Creaven M.,
RA Radomski N., Jost E., Lenoir G.M., Romeo G., Sylla B.S.;
RT "Molecular cloning and mapping of a human cDNA (PA2G4) that encodes a
RT protein highly homologous to the mouse cell cycle protein p38-2G4.";
RL Cytogenet. Cell Genet. 78:31-35(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH ERBB3, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=10682683; DOI=10.1054/bjoc.1999.0981;
RA Yoo J.Y., Wang X.W., Rishi A.K., Lessor T., Xia X.M., Gustafson T.A.,
RA Hamburger A.W.;
RT "Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of
RT this binding by heregulin.";
RL Br. J. Cancer 82:683-690(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Caroli F., Lamartine J., Sylla B.S., Romeo G., Seri M.;
RT "Genomic structure of the human PA2G4 gene.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP PROTEIN SEQUENCE OF 2-20; 23-30; 34-62; 73-101; 156-172; 200-211;
RP 216-236; 264-281 AND 299-364, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma, Mammary carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Matallanas D., Cooper W.N., Boldt K.,
RA von Kriegsheim A.F., Kolch W.;
RL Submitted (JAN-2010) to UniProtKB.
RN [6]
RP PROTEIN SEQUENCE OF 34-51; 216-236; 264-271; 299-311; 333-344 AND
RP 377-394, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP INTERACTION WITH ERBB3, PHOSPHORYLATION, PHOSPHORYLATION BY PKC,
RP PHOSPHORYLATION AT THR-366, AND MUTAGENESIS OF SER-363 AND THR-366.
RX PubMed=11325528; DOI=10.1016/S0303-7207(01)00387-2;
RA Lessor T.J., Hamburger A.W.;
RT "Regulation of the ErbB3 binding protein Ebp1 by protein kinase C.";
RL Mol. Cell. Endocrinol. 175:185-191(2001).
RN [8]
RP FUNCTION IN TRANSCRIPTION REPRESSION, AND INTERACTION WITH RB1.
RX PubMed=11268000; DOI=10.1002/jcp.1075;
RA Xia X., Cheng A., Lessor T., Zhang Y., Hamburger A.W.;
RT "Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb
RT transcriptional regulation.";
RL J. Cell. Physiol. 187:209-217(2001).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE
RP SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=12429849; DOI=10.1091/mbc.E02-05-0271;
RA Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C.,
RA Greco A., Hochstrasser D.F., Diaz J.-J.;
RT "Functional proteomic analysis of human nucleolus.";
RL Mol. Biol. Cell 13:4100-4109(2002).
RN [10]
RP FUNCTION IN E2F1-MEDIATED TRANSCRIPTION REPRESSION, AND INTERACTION
RP WITH HDAC2.
RX PubMed=12682367; DOI=10.1093/nar/gkg318;
RA Zhang Y., Woodford N., Xia X., Hamburger A.W.;
RT "Repression of E2F1-mediated transcription by the ErbB3 binding
RT protein Ebp1 involves histone deacetylases.";
RL Nucleic Acids Res. 31:2168-2177(2003).
RN [11]
RP FUNCTION IN RRNA PROCESSING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP RNA-BINDING, IDENTIFICATION IN A RIBONUCLEOPROTEIN COMPLEX,
RP ASSOCIATION WITH RRNA, ASSOCIATION WITH U3 SNORNA, AND MUTAGENESIS OF
RP 20-LYS--LYS-22 AND 364-ARG-LYS-365.
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 [12]
RP FUNCTION IN TRANSCRIPTION REPRESSION, AND INTERACTION WITH ERBB3 AND
RP AR.
RX PubMed=15583694; DOI=10.1038/sj.bjc.6602257;
RA Zhang Y., Hamburger A.W.;
RT "Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein
RT 1) mediated repression of androgen receptor signalling.";
RL Br. J. Cancer 92:140-146(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND THR-386, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-386, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361 AND THR-386, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-386, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2; SER-361 AND THR-386, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-2 AND THR-386, AND MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), INTERACTION WITH 5S RIBOSOMAL
RP RNA, LACK OF METAL COFACTOR, AND LACK OF AMINOPEPTIDASE ACTIVITY.
RX PubMed=17765895; DOI=10.1016/j.febslet.2007.08.024;
RA Kowalinski E., Bange G., Bradatsch B., Hurt E., Wild K., Sinning I.;
RT "The crystal structure of Ebp1 reveals a methionine aminopeptidase
RT fold as binding platform for multiple interactions.";
RL FEBS Lett. 581:4450-4454(2007).
CC -!- FUNCTION: May play a role in a ERBB3-regulated signal transduction
CC pathway. Seems be involved in growth regulation. Acts a
CC corepressor of the androgen receptor (AR) and is regulated by the
CC ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription
CC of some E2F1-regulated promoters, probably by recruiting histone
CC acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and
CC 5.8S mature rRNAs, several rRNA precursors and probably U3 small
CC nucleolar RNA. May be involved in regulation of intermediate and
CC late steps of rRNA processing. May be involved in ribosome
CC assembly. Mediates cap-independent translation of specific viral
CC IRESs (internal ribosomal entry site) (By similarity).
CC -!- SUBUNIT: Interacts with the cytoplasmic domain of non-
CC phosphorylated ERBB3; the interaction requires PKC activity.
CC Interacts with AR. Treatment with HRG leads to dissociation from
CC ERBB3 and increases association with AR. Interacts with
CC NCL/nucleolin. Component of a ribonucleoprotein complex containing
CC at least PA2G4, NCL, TOP1, PABPC2, RPLP0, acetylated histone H1
CC (HIST1H1A or H1F1), histone H1 2/4, RPL4, RPL8, RPL15, RPL18,
CC RPL18A, RPL21, RPL11, RPL12, RPL28, RPL27, RPLP2 and RPL24.
CC Interacts with HDAC2. Interacts with RB1; the interaction is
CC enhanced upon PA2G4 dephosphorylation.
CC -!- INTERACTION:
CC P19338:NCL; NbExp=2; IntAct=EBI-924893, EBI-346967;
CC P06400:RB1; NbExp=4; IntAct=EBI-924893, EBI-491274;
CC Q96ST3:SIN3A; NbExp=4; IntAct=EBI-924893, EBI-347218;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus.
CC Note=Tranlocates to the nucleus upon treatment with HRG.
CC -!- TISSUE SPECIFICITY: Expressed in several cell lines tested,
CC including primary and transformed cell lines.
CC -!- PTM: Phosphorylated on serine and threonine residues.
CC Phosphorylation is enhanced by HRG treatment. Basal
CC phosphorylation is PKC-dependent and HRG-induced phosphorylation
CC is predominantly PKC-independent.
CC -!- SIMILARITY: Belongs to the peptidase M24 family.
CC -!- CAUTION: Although it belongs to the peptidase M24 family, it does
CC not contain metal cofactors and lacks aminopeptidase activity.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD00646.1; Type=Erroneous initiation;
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PA2G4ID41628ch12q13.html";
CC -----------------------------------------------------------------------
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DR EMBL; U59435; AAB91536.1; -; mRNA.
DR EMBL; U87954; AAD00646.1; ALT_INIT; mRNA.
DR EMBL; AF104670; AAD05561.1; -; Genomic_DNA.
DR EMBL; AF104668; AAD05561.1; JOINED; Genomic_DNA.
DR EMBL; AF104669; AAD05561.1; JOINED; Genomic_DNA.
DR EMBL; BC001951; AAH01951.1; -; mRNA.
DR EMBL; BC007561; AAH07561.1; -; mRNA.
DR EMBL; BC069786; AAH69786.1; -; mRNA.
DR RefSeq; NP_006182.2; NM_006191.2.
DR UniGene; Hs.524498; -.
DR UniGene; Hs.745109; -.
DR PDB; 2Q8K; X-ray; 1.60 A; A=2-394.
DR PDB; 3J2I; EM; 11.90 A; A=1-394.
DR PDBsum; 2Q8K; -.
DR PDBsum; 3J2I; -.
DR ProteinModelPortal; Q9UQ80; -.
DR SMR; Q9UQ80; 7-362.
DR IntAct; Q9UQ80; 43.
DR MINT; MINT-5000754; -.
DR STRING; 9606.ENSP00000302886; -.
DR MEROPS; M24.973; -.
DR PhosphoSite; Q9UQ80; -.
DR DMDM; 13632817; -.
DR SWISS-2DPAGE; Q9UQ80; -.
DR PaxDb; Q9UQ80; -.
DR PRIDE; Q9UQ80; -.
DR DNASU; 5036; -.
DR Ensembl; ENST00000303305; ENSP00000302886; ENSG00000170515.
DR GeneID; 5036; -.
DR KEGG; hsa:5036; -.
DR UCSC; uc001sjm.3; human.
DR CTD; 5036; -.
DR GeneCards; GC12P056498; -.
DR HGNC; HGNC:8550; PA2G4.
DR HPA; CAB011711; -.
DR HPA; CAB012428; -.
DR HPA; HPA016484; -.
DR MIM; 602145; gene.
DR neXtProt; NX_Q9UQ80; -.
DR PharmGKB; PA32877; -.
DR eggNOG; COG0024; -.
DR HOGENOM; HOG000168207; -.
DR HOVERGEN; HBG053117; -.
DR InParanoid; Q9UQ80; -.
DR OMA; VWYKPEL; -.
DR OrthoDB; EOG7SFHXD; -.
DR PhylomeDB; Q9UQ80; -.
DR EvolutionaryTrace; Q9UQ80; -.
DR GeneWiki; PA2G4; -.
DR GenomeRNAi; 5036; -.
DR NextBio; 19404; -.
DR PRO; PR:Q9UQ80; -.
DR ArrayExpress; Q9UQ80; -.
DR Bgee; Q9UQ80; -.
DR CleanEx; HS_PA2G4; -.
DR Genevestigator; Q9UQ80; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0030529; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IDA:MGI.
DR GO; GO:0007050; P:cell cycle arrest; TAS:ProtInc.
DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:MGI.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.90.230.10; -; 2.
DR InterPro; IPR004545; Pap_1.
DR InterPro; IPR000994; Pept_M24_structural-domain.
DR InterPro; IPR018349; Pept_M24A_MAP2_BS.
DR InterPro; IPR011991; WHTH_DNA-bd_dom.
DR Pfam; PF00557; Peptidase_M24; 1.
DR SUPFAM; SSF55920; SSF55920; 2.
DR TIGRFAMs; TIGR00495; crvDNA_42K; 1.
DR PROSITE; PS01202; MAP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Ribonucleoprotein; RNA-binding;
KW rRNA processing; Transcription; Transcription regulation;
KW Translation regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 394 Proliferation-associated protein 2G4.
FT /FTId=PRO_0000148989.
FT REGION 2 48 Necessary for nucleolar localization.
FT REGION 46 54 RNA-binding.
FT REGION 301 394 Necessary for nucleolar localization.
FT REGION 361 375 Interaction with RNA (By similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 2 2 Phosphoserine.
FT MOD_RES 361 361 Phosphoserine.
FT MOD_RES 366 366 Phosphothreonine (Probable).
FT MOD_RES 386 386 Phosphothreonine.
FT MUTAGEN 20 22 KYK->AYA: Loss of nucleolar localization.
FT MUTAGEN 363 363 S->A: No effect on in vitro
FT phosphorylation by PKC.
FT MUTAGEN 364 365 RK->AA: Only partial nucleolar
FT localization.
FT MUTAGEN 366 366 T->A: Decreases in vitro phosphorylation
FT by PKC.
FT CONFLICT 381 381 A -> P (in Ref. 1; AAB91536).
FT HELIX 15 38
FT HELIX 45 61
FT STRAND 72 82
FT STRAND 85 87
FT STRAND 105 114
FT STRAND 117 126
FT HELIX 137 156
FT HELIX 163 175
FT TURN 176 178
FT STRAND 186 191
FT STRAND 194 196
FT STRAND 200 204
FT HELIX 207 212
FT STRAND 223 233
FT STRAND 246 249
FT HELIX 260 273
FT HELIX 280 282
FT HELIX 287 298
FT STRAND 301 305
FT STRAND 316 326
FT STRAND 329 332
FT HELIX 340 342
FT HELIX 352 359
SQ SEQUENCE 394 AA; 43787 MW; CD45466507AD6047 CRC64;
MSGEDEQQEQ TIAEDLVVTK YKMGGDIANR VLRSLVEASS SGVSVLSLCE KGDAMIMEET
GKIFKKEKEM KKGIAFPTSI SVNNCVCHFS PLKSDQDYIL KEGDLVKIDL GVHVDGFIAN
VAHTFVVDVA QGTQVTGRKA 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 EAGD
//
MIM
602145
*RECORD*
*FIELD* NO
602145
*FIELD* TI
*602145 PROLIFERATION-ASSOCIATED 2G4, 38-KD; PA2G4
;;ERBB3-BINDING PROTEIN 1; EBP1
read more*FIELD* TX
CLONING
The mouse Pa2g4 gene was isolated by Radomski and Jost (1995) by
screening a cDNA expression library from a murine macrophage cell line
with the antibody mAb2G4. This monoclonal antibody was generated against
a single-stranded DNA-binding protein to identify proteins showing cell
cycle specific variation in nuclear localization. The protein encoded by
Pa2g4, p38-2G4, was shown to be confined to the nucleus during
interphase and early prophase, but distributed throughout the cytoplasm
from metaphase through to telophase. In addition, p38-2G4 was found to
be highly expressed between G1 and mid-S phase, decreasing toward the
end of S phase and ceasing at the S/G2 transition. As the protein is
expressed in response to mitogen stimulation, it may belong to a large
family of cell cycle regulatory proteins or replication proteins that
maintain the cell cycle activities of proliferating cells. It appears to
be a proliferation-dependent gene that probably encodes a nuclear
DNA-binding protein involved in the control of cell replication.
Lamartine et al. (1997) isolated and characterized human PA2G4. A cDNA
of 1,697 nucleotides was predicted to encode a protein of 394 amino
acids. The deduced amino acid sequence of this human protein showed very
strong homology to the mouse protein p38-2G4.
Liu et al. (2006) identified isoforms of Ebp1 with apparent molecular
masses of 48 and 42 kD by SDS-PAGE in the rat PC12 pheochromocytoma cell
line. The 48-kD isoform (p48) localized to both the cytoplasm and
nucleus of PC12 cells, whereas the 42-kD isoform (p42) was predominantly
localized in the cytoplasm.
GENE FUNCTION
Liu et al. (2006) found that the p48 isoform of Ebp1 suppressed
apoptosis in rat PC12 cells, whereas the cytoplasmic p42 isoform
promoted cell differentiation. EGF (131530) stimulated p42 to bind ERBB3
(190151) in transfected human embryonic kidney cells, and the
association depended on PKC (see PRKCA; 176960)-mediated phosphorylation
of p42. p48 did not bind ERBB3 regardless of EGF treatment.
Overexpression of p48 induced PC12 cell proliferation, which was
inhibited by p42. Nerve growth factor (NGFB; 162030) elicited extensive
sprouting in p42-transfected PC12 cells, whereas p48 induced only modest
neurite outgrowth. Akt (AKT1; 164730) was more active in p48 cells than
in p42 cells. Liu et al. (2006) concluded that EBP1 may regulate cell
survival and differentiation through 2 distinctive isoforms.
MAPPING
Lamartine et al. (1997) concluded that PA2G4 belongs to a gene family
with members in several chromosome regions: 3q24-q25, 6q22, 9q21, 12q13,
18q12, 20p12, and Xq25. They suggested that the human PA2G4 cDNA they
analyzed probably corresponds to a functional copy at chromosome 12q13.
*FIELD* RF
1. Lamartine, J.; Seri, M.; Cinti, R.; Heitzmann, F.; Creaven, M.;
Radomski, N.; Jost, E.; Lenoir, G. M.; Romeo, G.; Sylla, B. S.: Molecular
cloning and mapping of a human cDNA (PA2G4) that encodes a protein
highly homologous to the mouse cell cycle protein p38-2G4. Cytogenet.
Cell Genet. 78: 31-35, 1997.
2. Liu, Z.; Ahn, J.-Y.; Liu, X.; Ye, K.: Ebp1 isoforms distinctively
regulate cell survival and differentiation. Proc. Nat. Acad. Sci. 103:
10917-10922, 2006.
3. Radomski, N.; Jost, E.: Molecular cloning of a murine cDNA encoding
a novel protein, p38-2G4, which varies with the cell cycle. Exp.
Cell Res. 220: 434-445, 1995.
*FIELD* CN
Patricia A. Hartz - updated: 10/3/2006
*FIELD* CD
Victor A. McKusick: 12/3/1997
*FIELD* ED
mgross: 10/05/2006
terry: 10/3/2006
terry: 12/7/2001
dkim: 7/30/1998
dholmes: 1/23/1998
alopez: 12/15/1997
dholmes: 12/4/1997
*RECORD*
*FIELD* NO
602145
*FIELD* TI
*602145 PROLIFERATION-ASSOCIATED 2G4, 38-KD; PA2G4
;;ERBB3-BINDING PROTEIN 1; EBP1
read more*FIELD* TX
CLONING
The mouse Pa2g4 gene was isolated by Radomski and Jost (1995) by
screening a cDNA expression library from a murine macrophage cell line
with the antibody mAb2G4. This monoclonal antibody was generated against
a single-stranded DNA-binding protein to identify proteins showing cell
cycle specific variation in nuclear localization. The protein encoded by
Pa2g4, p38-2G4, was shown to be confined to the nucleus during
interphase and early prophase, but distributed throughout the cytoplasm
from metaphase through to telophase. In addition, p38-2G4 was found to
be highly expressed between G1 and mid-S phase, decreasing toward the
end of S phase and ceasing at the S/G2 transition. As the protein is
expressed in response to mitogen stimulation, it may belong to a large
family of cell cycle regulatory proteins or replication proteins that
maintain the cell cycle activities of proliferating cells. It appears to
be a proliferation-dependent gene that probably encodes a nuclear
DNA-binding protein involved in the control of cell replication.
Lamartine et al. (1997) isolated and characterized human PA2G4. A cDNA
of 1,697 nucleotides was predicted to encode a protein of 394 amino
acids. The deduced amino acid sequence of this human protein showed very
strong homology to the mouse protein p38-2G4.
Liu et al. (2006) identified isoforms of Ebp1 with apparent molecular
masses of 48 and 42 kD by SDS-PAGE in the rat PC12 pheochromocytoma cell
line. The 48-kD isoform (p48) localized to both the cytoplasm and
nucleus of PC12 cells, whereas the 42-kD isoform (p42) was predominantly
localized in the cytoplasm.
GENE FUNCTION
Liu et al. (2006) found that the p48 isoform of Ebp1 suppressed
apoptosis in rat PC12 cells, whereas the cytoplasmic p42 isoform
promoted cell differentiation. EGF (131530) stimulated p42 to bind ERBB3
(190151) in transfected human embryonic kidney cells, and the
association depended on PKC (see PRKCA; 176960)-mediated phosphorylation
of p42. p48 did not bind ERBB3 regardless of EGF treatment.
Overexpression of p48 induced PC12 cell proliferation, which was
inhibited by p42. Nerve growth factor (NGFB; 162030) elicited extensive
sprouting in p42-transfected PC12 cells, whereas p48 induced only modest
neurite outgrowth. Akt (AKT1; 164730) was more active in p48 cells than
in p42 cells. Liu et al. (2006) concluded that EBP1 may regulate cell
survival and differentiation through 2 distinctive isoforms.
MAPPING
Lamartine et al. (1997) concluded that PA2G4 belongs to a gene family
with members in several chromosome regions: 3q24-q25, 6q22, 9q21, 12q13,
18q12, 20p12, and Xq25. They suggested that the human PA2G4 cDNA they
analyzed probably corresponds to a functional copy at chromosome 12q13.
*FIELD* RF
1. Lamartine, J.; Seri, M.; Cinti, R.; Heitzmann, F.; Creaven, M.;
Radomski, N.; Jost, E.; Lenoir, G. M.; Romeo, G.; Sylla, B. S.: Molecular
cloning and mapping of a human cDNA (PA2G4) that encodes a protein
highly homologous to the mouse cell cycle protein p38-2G4. Cytogenet.
Cell Genet. 78: 31-35, 1997.
2. Liu, Z.; Ahn, J.-Y.; Liu, X.; Ye, K.: Ebp1 isoforms distinctively
regulate cell survival and differentiation. Proc. Nat. Acad. Sci. 103:
10917-10922, 2006.
3. Radomski, N.; Jost, E.: Molecular cloning of a murine cDNA encoding
a novel protein, p38-2G4, which varies with the cell cycle. Exp.
Cell Res. 220: 434-445, 1995.
*FIELD* CN
Patricia A. Hartz - updated: 10/3/2006
*FIELD* CD
Victor A. McKusick: 12/3/1997
*FIELD* ED
mgross: 10/05/2006
terry: 10/3/2006
terry: 12/7/2001
dkim: 7/30/1998
dholmes: 1/23/1998
alopez: 12/15/1997
dholmes: 12/4/1997