Q9UQ80 (PA2G4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Proliferation-associated protein 2G4

Alternative name(s):
Cell cycle protein p38-2G4 homolog
Short name=hG4-1
ErbB3-binding protein 1

Gene names

Name:	PA2G4
Synonyms:	EBP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	394 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in a ERBB3-regulated signal transduction pathway. Seems be involved in growth regulation. Acts a corepressor of the androgen receptor (AR) and is regulated by the ERBB3 ligand neuregulin-1/heregulin (HRG). Inhibits transcription of some E2F1-regulated promoters, probably by recruiting histone acetylase (HAT) activity. Binds RNA. Associates with 28S, 18S and 5.8S mature rRNAs, several rRNA precursors and probably U3 small nucleolar RNA. May be involved in regulation of intermediate and late steps of rRNA processing. May be involved in ribosome assembly. Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site) By similarity. Ref.8 Ref.10 Ref.11 Ref.12
Subunit structure	Interacts with the cytoplasmic domain of non-phosphorylated ERBB3; the interaction requires PKC activity. Interacts with AR. Treatment with HRG leads to dissociation from ERBB3 and increases association with AR. Interacts with NCL/nucleolin. Component of a ribonucleoprotein complex containing at least PA2G4, NCL, TOP1, PABPC2, RPLP0, acetylated histone H1 (HIST1H1A or H1F1), histone H1 2/4, RPL4, RPL8, RPL15, RPL18, RPL18A, RPL21, RPL11, RPL12, RPL28, RPL27, RPLP2 and RPL24. Interacts with HDAC2. Interacts with RB1; the interaction is enhanced upon PA2G4 dephosphorylation. Ref.2 Ref.7 Ref.8 Ref.10 Ref.11 Ref.12 Ref.20
Subcellular location	Cytoplasm. Nucleus › nucleolus. Note: Tranlocates to the nucleus upon treatment with HRG. Ref.2 Ref.9 Ref.11
Tissue specificity	Expressed in several cell lines tested, including primary and transformed cell lines. Ref.11
Post-translational modification	Phosphorylated on serine and threonine residues. Phosphorylation is enhanced by HRG treatment. Basal phosphorylation is PKC-dependent and HRG-induced phosphorylation is predominantly PKC-independent. Ref.7
Sequence similarities	Belongs to the peptidase M24 family.
Caution	Although it belongs to the peptidase M24 family, it does not contain metal cofactors and lacks aminopeptidase activity.
Sequence caution	The sequence AAD00646.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Translation regulation rRNA processing
Cellular component	Cytoplasm Nucleus
Ligand	RNA-binding
Molecular function	Repressor Ribonucleoprotein
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle arrest Traceable author statement PubMed 7556453. Source: ProtInc cell proliferation Traceable author statement PubMed 7556453. Source: ProtInc negative regulation of transcription, DNA-dependent Inferred from direct assay PubMed 15073182. Source: MGI rRNA processing Inferred from electronic annotation. Source: UniProtKB-KW regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay PubMed 19037095. Source: UniProtKB nucleolus Inferred from direct assay PubMed 19037095. Source: UniProtKB ribonucleoprotein complex Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA binding Inferred from direct assay PubMed 15073182. Source: MGI RNA binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 15073182. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCL	P19338	2	EBI-924893,EBI-346967
RB1	P06400	4	EBI-924893,EBI-491274
SIN3A	Q96ST3	4	EBI-924893,EBI-347218

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.5

Chain

2 – 394

393

Proliferation-associated protein 2G4

PRO_0000148989

Regions

Region

2 – 48

47

Necessary for nucleolar localization

Region

46 – 54

9

RNA-binding

Region

301 – 394

94

Necessary for nucleolar localization

Region

361 – 375

15

Interaction with RNA By similarity

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.5 Ref.17 Ref.19

Modified residue

2

1

Phosphoserine Ref.13 Ref.17 Ref.19

Modified residue

361

1

Phosphoserine Ref.15 Ref.17

Modified residue

366

1

Phosphothreonine Probable

Modified residue

386

1

Phosphothreonine Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.19

Experimental info

Mutagenesis

20 – 22

3

KYK → AYA: Loss of nucleolar localization. Ref.11

Mutagenesis

363

1

S → A: No effect on in vitro phosphorylation by PKC. Ref.7

Mutagenesis

364 – 365

2

RK → AA: Only partial nucleolar localization.

Mutagenesis

366

1

T → A: Decreases in vitro phosphorylation by PKC. Ref.7

Sequence conflict

381

1

A → P in AAB91536. Ref.1

Secondary structure

1

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394

Helix Strand Turn

Details...

Helix

15 – 38

24

Helix

45 – 61

17

Beta strand

72 – 82

11

Beta strand

85 – 87

3

Beta strand

105 – 114

10

Beta strand

117 – 126

10

Helix

137 – 156

20

Helix

163 – 175

13

Turn

176 – 178

3

Beta strand

186 – 191

6

Beta strand

194 – 196

3

Beta strand

200 – 204

5

Helix

207 – 212

6

Beta strand

223 – 233

11

Beta strand

246 – 249

4

Helix

260 – 273

14

Helix

280 – 282

3

Helix

287 – 298

12

Beta strand

301 – 305

5

Beta strand

316 – 326

11

Beta strand

329 – 332

4

Helix

340 – 342

3

Helix

352 – 359

8

Sequences

	Sequence		Length	Mass (Da)
	Q9UQ80 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: CD45466507AD6047	FASTA	394	43,787
	10 20 30 40 50 60 MSGEDEQQEQ TIAEDLVVTK YKMGGDIANR VLRSLVEASS SGVSVLSLCE KGDAMIMEET 70 80 90 100 110 120 GKIFKKEKEM KKGIAFPTSI SVNNCVCHFS PLKSDQDYIL KEGDLVKIDL GVHVDGFIAN 130 140 150 160 170 180 VAHTFVVDVA QGTQVTGRKA DVIKAAHLCA EAALRLVKPG NQNTQVTEAW NKVAHSFNCT 190 200 210 220 230 240 PIEGMLSHQL KQHVIDGEKT IIQNPTDQQK KDHEKAEFEV HEVYAVDVLV SSGEGKAKDA 250 260 270 280 290 300 GQRTTIYKRD PSKQYGLKMK TSRAFFSEVE RRFDAMPFTL RAFEDEKKAR MGVVECAKHE 310 320 330 340 350 360 LLQPFNVLYE KEGEFVAQFK FTVLLMPNGP MRITSGPFEP DLYKSEMEVQ DAELKALLQS 370 380 390 SASRKTQKKK KKKASKTAEN ATSGETLEEN EAGD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and mapping of a human cDNA (PA2G4) that encodes a protein highly homologous to the mouse cell cycle protein p38-2G4." Lamartine J., Seri M., Cinti R., Heitzmann F., Creaven M., Radomski N., Jost E., Lenoir G.M., Romeo G., Sylla B.S. Cytogenet. Cell Genet. 78:31-35(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Interaction of the PA2G4 (EBP1) protein with ErbB-3 and regulation of this binding by heregulin." Yoo J.Y., Wang X.W., Rishi A.K., Lessor T., Xia X.M., Gustafson T.A., Hamburger A.W. Br. J. Cancer 82:683-690(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH ERBB3, SUBCELLULAR LOCATION. Tissue: Brain.
[3]	"Genomic structure of the human PA2G4 gene." Caroli F., Lamartine J., Sylla B.S., Romeo G., Seri M. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Skin.
[5]	Bienvenut W.V., Matallanas D., Cooper W.N., Boldt K., von Kriegsheim A.F., Kolch W. Submitted (JAN-2010) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-20; 23-30; 34-62; 73-101; 156-172; 200-211; 216-236; 264-281 AND 299-364, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma, Mammary carcinoma and Ovarian carcinoma.
[6]	Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 34-51; 216-236; 264-271; 299-311; 333-344 AND 377-394, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[7]	"Regulation of the ErbB3 binding protein Ebp1 by protein kinase C." Lessor T.J., Hamburger A.W. Mol. Cell. Endocrinol. 175:185-191(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ERBB3, PHOSPHORYLATION, PHOSPHORYLATION BY PKC, PHOSPHORYLATION AT THR-366, MUTAGENESIS OF SER-363 AND THR-366.
[8]	"Ebp1, an ErbB-3 binding protein, interacts with Rb and affects Rb transcriptional regulation." Xia X., Cheng A., Lessor T., Zhang Y., Hamburger A.W. J. Cell. Physiol. 187:209-217(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TRANSCRIPTION REPRESSION, INTERACTION WITH RB1.
[9]	"Functional proteomic analysis of human nucleolus." Scherl A., Coute Y., Deon C., Calle A., Kindbeiter K., Sanchez J.-C., Greco A., Hochstrasser D.F., Diaz J.-J. Mol. Biol. Cell 13:4100-4109(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[10]	"Repression of E2F1-mediated transcription by the ErbB3 binding protein Ebp1 involves histone deacetylases." Zhang Y., Woodford N., Xia X., Hamburger A.W. Nucleic Acids Res. 31:2168-2177(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN E2F1-MEDIATED TRANSCRIPTION REPRESSION, INTERACTION WITH HDAC2.
[11]	"EBP1 is a nucleolar growth-regulating protein that is part of pre-ribosomal ribonucleoprotein complexes." Squatrito M., Mancino M., Donzelli M., Areces L.B., Draetta G.F. Oncogene 23:4454-4465(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RRNA PROCESSING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RNA-BINDING, IDENTIFICATION IN A RIBONUCLEOPROTEIN COMPLEX, ASSOCIATION WITH RRNA, ASSOCIATION WITH U3 SNORNA, MUTAGENESIS OF 20-LYS--LYS-22 AND 364-ARG-LYS-365.
[12]	"Specificity and heregulin regulation of Ebp1 (ErbB3 binding protein 1) mediated repression of androgen receptor signalling." Zhang Y., Hamburger A.W. Br. J. Cancer 92:140-146(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN TRANSCRIPTION REPRESSION, INTERACTION WITH ERBB3 AND AR.
[13]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND THR-386, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-386, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361 AND THR-386, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-386, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[17]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2; SER-361 AND THR-386, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND THR-386, MASS SPECTROMETRY.
[20]	"The crystal structure of Ebp1 reveals a methionine aminopeptidase fold as binding platform for multiple interactions." Kowalinski E., Bange G., Bradatsch B., Hurt E., Wild K., Sinning I. FEBS Lett. 581:4450-4454(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), INTERACTION WITH 5S RIBOSOMAL RNA, LACK OF METAL COFACTOR, LACK OF AMINOPEPTIDASE ACTIVITY.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U59435 mRNA. Translation: AAB91536.1.
U87954 mRNA. Translation: AAD00646.1. Different initiation.
AF104670, AF104668, AF104669 Genomic DNA. Translation: AAD05561.1.
BC001951 mRNA. Translation: AAH01951.1.
BC007561 mRNA. Translation: AAH07561.1.
BC069786 mRNA. Translation: AAH69786.1.

IPI

IPI00299000.

RefSeq

NP_006182.2. NM_006191.2.

UniGene

Hs.524498.
Hs.573018.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Q8K	X-ray	1.60	A	2-394	[»]
3J2I	electron microscopy	11.90	A	1-394	[»]

ProteinModelPortal

Q9UQ80.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UQ80. 42 interactions.

MINT

MINT-5000754.

STRING

9606.ENSP00000302886.

Protein family/group databases

MEROPS

M24.973.

PTM databases

PhosphoSite

Q9UQ80.

Polymorphism databases

DMDM

13632817.

2D gel databases

SWISS-2DPAGE

Q9UQ80.

Proteomic databases

PaxDb

Q9UQ80.

PRIDE

Q9UQ80.

Protocols and materials databases

DNASU

5036.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000303305; ENSP00000302886; ENSG00000170515.

GeneID

5036.

KEGG

hsa:5036.

UCSC

uc001sjm.3. human.

Organism-specific databases

CTD

5036.

GeneCards

GC12P056498.

HGNC

HGNC:8550. PA2G4.

HPA

CAB011711.
CAB012428.
HPA016484.

MIM

602145. gene.

neXtProt

NX_Q9UQ80.

PharmGKB

PA32877.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0024.

HOGENOM

HOG000168207.

HOVERGEN

HBG053117.

InParanoid

Q9UQ80.

OrthoDB

EOG4J6RR6.

PhylomeDB

Q9UQ80.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.

Gene expression databases

ArrayExpress

Q9UQ80.

Bgee

Q9UQ80.

CleanEx

HS_PA2G4.

Genevestigator

Q9UQ80.

GermOnline

ENSG00000170515. Homo sapiens.

Family and domain databases

Gene3D

1.10.10.10. 1 hit.
3.90.230.10. 2 hits.

InterPro

IPR004545. Pap_1.
IPR000994. Pept_M24_structural-domain.
IPR018349. Pept_M24A_MAP2_BS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]

Pfam

PF00557. Peptidase_M24. 1 hit.
[Graphical view]

SUPFAM

SSF55920. Peptidase_M24_cat_core. 1 hit.

TIGRFAMs

TIGR00495. crvDNA_42K. 1 hit.

PROSITE

PS01202. MAP_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9UQ80.

GenomeRNAi

5036.

NextBio

19404.

SOURCE

Search...

Entry information

Entry name

PA2G4_HUMAN

Accession

Primary (citable) accession number: Q9UQ80
Secondary accession number(s): O43846, Q9UM59

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	January 23, 2007
Last modified:	May 29, 2013
This is version 134 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.