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Protein

Proliferation-associated protein 2G4

Gene

PA2G4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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). Regulates cell proliferation, differentiation, and survival. Isoform 1 suppresses apoptosis whereas isoform 2 promotes cell differentiation (By similarity).By similarity5 Publications

GO - Molecular functioni

  • DNA binding Source: MGI
  • poly(A) RNA binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: MGI
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • cell cycle arrest Source: ProtInc
  • cell proliferation Source: ProtInc
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: MGI
  • positive regulation of cell differentiation Source: UniProtKB
  • regulation of translation Source: UniProtKB-KW
  • rRNA processing Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor, Ribonucleoprotein

Keywords - Biological processi

rRNA processing, Transcription, Transcription regulation, Translation regulation

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170515-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
SIGNORiQ9UQ80.

Protein family/group databases

MEROPSiM24.973.

Names & Taxonomyi

Protein namesi
Recommended name:
Proliferation-associated protein 2G4
Alternative name(s):
Cell cycle protein p38-2G4 homolog
Short name:
hG4-1
ErbB3-binding protein 1
Gene namesi
Name:PA2G4
Synonyms:EBP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:8550. PA2G4.

Subcellular locationi

Isoform 1 :
Isoform 2 :

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • intracellular ribonucleoprotein complex Source: UniProtKB-KW
  • membrane Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20 – 22KYK → AYA: Loss of nucleolar localization. 1 Publication3
Mutagenesisi361S → A: Loss of phosphorylation and interaction with ERBB3 and HUWE1. 1 Publication1
Mutagenesisi361S → D: No effect on phosphorylation and loss of nucleolar localization. 1 Publication1
Mutagenesisi363S → A: No effect on in vitro phosphorylation by PKC. 1 Publication1
Mutagenesisi364 – 365RK → AA: Only partial nucleolar localization. 1 Publication2
Mutagenesisi366T → A: Decreases in vitro phosphorylation by PKC. 1 Publication1

Organism-specific databases

DisGeNETi5036.
OpenTargetsiENSG00000170515.
PharmGKBiPA32877.

Polymorphism and mutation databases

BioMutaiPA2G4.
DMDMi13632817.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001489892 – 394Proliferation-associated protein 2G4Add BLAST393

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1 Publication1
Modified residuei2PhosphoserineCombined sources1
Modified residuei335PhosphoserineCombined sources1
Modified residuei361Phosphoserine; by PKC/PRKCDCombined sources1 Publication1
Modified residuei366Phosphothreonine1 Publication1
Modified residuei386PhosphothreonineCombined sources1

Post-translational modificationi

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. Phosphorylation at Ser-361 by PKC/PRKCD regulates its nucleolar localization.3 Publications
In cancer cells, isoform 2 is polyubiquitinated leading to its proteasomal degradation and phosphorylation by PKC/PRKCD enhances polyubiquitination.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UQ80.
PaxDbiQ9UQ80.
PeptideAtlasiQ9UQ80.
PRIDEiQ9UQ80.

2D gel databases

SWISS-2DPAGEQ9UQ80.

PTM databases

iPTMnetiQ9UQ80.
PhosphoSitePlusiQ9UQ80.
SwissPalmiQ9UQ80.

Expressioni

Tissue specificityi

Isoform 2 is undetectable whereas isoform 1 is strongly expressed in cancer cells (at protein level). Isoform 1 and isoform 2 are widely expressed, including heart, brain, lung, pancreas, skeletal muscle, kidney, placenta and liver.3 Publications

Gene expression databases

BgeeiENSG00000170515.
CleanExiHS_PA2G4.
ExpressionAtlasiQ9UQ80. baseline and differential.
GenevisibleiQ9UQ80. HS.

Organism-specific databases

HPAiCAB011711.
CAB012428.
HPA016484.
HPA061845.

Interactioni

Subunit structurei

Isoform 2 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. Interacts with AKT1 (By similarity). Isoform 1 and isoform 2 interact with RNF20. Isoform 2 interacts with HUWE1. Interacts with DNAJC21 (PubMed:27346687).By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NCLP193382EBI-924893,EBI-346967
RB1P064004EBI-924893,EBI-491274
SIN3AQ96ST34EBI-924893,EBI-347218

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111075. 104 interactors.
DIPiDIP-31275N.
IntActiQ9UQ80. 57 interactors.
MINTiMINT-5000754.
STRINGi9606.ENSP00000302886.

Structurei

Secondary structure

1394
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi15 – 38Combined sources24
Helixi45 – 61Combined sources17
Beta strandi72 – 82Combined sources11
Beta strandi85 – 87Combined sources3
Beta strandi105 – 114Combined sources10
Beta strandi117 – 126Combined sources10
Helixi137 – 156Combined sources20
Helixi163 – 175Combined sources13
Turni176 – 178Combined sources3
Beta strandi186 – 191Combined sources6
Beta strandi194 – 196Combined sources3
Beta strandi200 – 204Combined sources5
Helixi207 – 212Combined sources6
Beta strandi223 – 233Combined sources11
Beta strandi246 – 249Combined sources4
Helixi260 – 273Combined sources14
Helixi280 – 282Combined sources3
Helixi287 – 298Combined sources12
Beta strandi301 – 305Combined sources5
Beta strandi316 – 326Combined sources11
Beta strandi329 – 332Combined sources4
Helixi340 – 342Combined sources3
Helixi352 – 359Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Q8KX-ray1.60A2-394[»]
3J2Ielectron microscopy11.90A1-394[»]
ProteinModelPortaliQ9UQ80.
SMRiQ9UQ80.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UQ80.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 48Necessary for nucleolar localization1 PublicationAdd BLAST47
Regioni46 – 54RNA-binding1 Publication9
Regioni301 – 394Necessary for nucleolar localization1 PublicationAdd BLAST94
Regioni361 – 375Interaction with RNABy similarityAdd BLAST15

Sequence similaritiesi

Belongs to the peptidase M24 family.Curated

Phylogenomic databases

eggNOGiKOG2776. Eukaryota.
COG0024. LUCA.
GeneTreeiENSGT00530000063220.
HOGENOMiHOG000168207.
HOVERGENiHBG053117.
InParanoidiQ9UQ80.
OMAiTHEVYAM.
OrthoDBiEOG091G0B89.
PhylomeDBiQ9UQ80.
TreeFamiTF300010.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
3.90.230.10. 2 hits.
InterProiIPR004545. PA2G4.
IPR000994. Pept_M24.
IPR018349. Pept_M24A_MAP2_BS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00557. Peptidase_M24. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF55920. SSF55920. 2 hits.
TIGRFAMsiTIGR00495. crvDNA_42K. 1 hit.
PROSITEiPS01202. MAP_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1Curated (identifier: Q9UQ80-1) [UniParc]FASTAAdd to basket
Also known as: p481 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSGEDEQQEQ TIAEDLVVTK YKMGGDIANR VLRSLVEASS SGVSVLSLCE
60 70 80 90 100
KGDAMIMEET GKIFKKEKEM KKGIAFPTSI SVNNCVCHFS PLKSDQDYIL
110 120 130 140 150
KEGDLVKIDL GVHVDGFIAN VAHTFVVDVA QGTQVTGRKA DVIKAAHLCA
160 170 180 190 200
EAALRLVKPG NQNTQVTEAW NKVAHSFNCT PIEGMLSHQL KQHVIDGEKT
210 220 230 240 250
IIQNPTDQQK KDHEKAEFEV HEVYAVDVLV SSGEGKAKDA GQRTTIYKRD
260 270 280 290 300
PSKQYGLKMK TSRAFFSEVE RRFDAMPFTL RAFEDEKKAR MGVVECAKHE
310 320 330 340 350
LLQPFNVLYE KEGEFVAQFK FTVLLMPNGP MRITSGPFEP DLYKSEMEVQ
360 370 380 390
DAELKALLQS SASRKTQKKK KKKASKTAEN ATSGETLEEN EAGD
Length:394
Mass (Da):43,787
Last modified:January 23, 2007 - v3
Checksum:iCD45466507AD6047
GO
Isoform 2Curated (identifier: Q9UQ80-2) [UniParc]FASTAAdd to basket
Also known as: p421 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: Missing.

Show »
Length:340
Mass (Da):38,059
Checksum:i639A83ADD56290A3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti381A → P in AAB91536 (PubMed:9345902).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0573251 – 54Missing in isoform 2. 1 PublicationAdd BLAST54

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U59435 mRNA. Translation: AAB91536.1.
U87954 mRNA. Translation: AAD00646.1.
AF104670, AF104668, AF104669 Genomic DNA. Translation: AAD05561.1.
BC001951 mRNA. Translation: AAH01951.1.
BC007561 mRNA. Translation: AAH07561.1.
BC069786 mRNA. Translation: AAH69786.1.
CCDSiCCDS8902.1. [Q9UQ80-1]
RefSeqiNP_006182.2. NM_006191.2. [Q9UQ80-1]
UniGeneiHs.524498.
Hs.745109.

Genome annotation databases

EnsembliENST00000303305; ENSP00000302886; ENSG00000170515. [Q9UQ80-1]
GeneIDi5036.
KEGGihsa:5036.
UCSCiuc001sjm.4. human. [Q9UQ80-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U59435 mRNA. Translation: AAB91536.1.
U87954 mRNA. Translation: AAD00646.1.
AF104670, AF104668, AF104669 Genomic DNA. Translation: AAD05561.1.
BC001951 mRNA. Translation: AAH01951.1.
BC007561 mRNA. Translation: AAH07561.1.
BC069786 mRNA. Translation: AAH69786.1.
CCDSiCCDS8902.1. [Q9UQ80-1]
RefSeqiNP_006182.2. NM_006191.2. [Q9UQ80-1]
UniGeneiHs.524498.
Hs.745109.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Q8KX-ray1.60A2-394[»]
3J2Ielectron microscopy11.90A1-394[»]
ProteinModelPortaliQ9UQ80.
SMRiQ9UQ80.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111075. 104 interactors.
DIPiDIP-31275N.
IntActiQ9UQ80. 57 interactors.
MINTiMINT-5000754.
STRINGi9606.ENSP00000302886.

Protein family/group databases

MEROPSiM24.973.

PTM databases

iPTMnetiQ9UQ80.
PhosphoSitePlusiQ9UQ80.
SwissPalmiQ9UQ80.

Polymorphism and mutation databases

BioMutaiPA2G4.
DMDMi13632817.

2D gel databases

SWISS-2DPAGEQ9UQ80.

Proteomic databases

EPDiQ9UQ80.
PaxDbiQ9UQ80.
PeptideAtlasiQ9UQ80.
PRIDEiQ9UQ80.

Protocols and materials databases

DNASUi5036.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000303305; ENSP00000302886; ENSG00000170515. [Q9UQ80-1]
GeneIDi5036.
KEGGihsa:5036.
UCSCiuc001sjm.4. human. [Q9UQ80-1]

Organism-specific databases

CTDi5036.
DisGeNETi5036.
GeneCardsiPA2G4.
HGNCiHGNC:8550. PA2G4.
HPAiCAB011711.
CAB012428.
HPA016484.
HPA061845.
MIMi602145. gene.
neXtProtiNX_Q9UQ80.
OpenTargetsiENSG00000170515.
PharmGKBiPA32877.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2776. Eukaryota.
COG0024. LUCA.
GeneTreeiENSGT00530000063220.
HOGENOMiHOG000168207.
HOVERGENiHBG053117.
InParanoidiQ9UQ80.
OMAiTHEVYAM.
OrthoDBiEOG091G0B89.
PhylomeDBiQ9UQ80.
TreeFamiTF300010.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170515-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
SIGNORiQ9UQ80.

Miscellaneous databases

ChiTaRSiPA2G4. human.
EvolutionaryTraceiQ9UQ80.
GeneWikiiPA2G4.
GenomeRNAii5036.
PROiQ9UQ80.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170515.
CleanExiHS_PA2G4.
ExpressionAtlasiQ9UQ80. baseline and differential.
GenevisibleiQ9UQ80. HS.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
3.90.230.10. 2 hits.
InterProiIPR004545. PA2G4.
IPR000994. Pept_M24.
IPR018349. Pept_M24A_MAP2_BS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00557. Peptidase_M24. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF55920. SSF55920. 2 hits.
TIGRFAMsiTIGR00495. crvDNA_42K. 1 hit.
PROSITEiPS01202. MAP_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPA2G4_HUMAN
AccessioniPrimary (citable) accession number: Q9UQ80
Secondary accession number(s): O43846, Q9UM59
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 171 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Caution

Although it belongs to the peptidase M24 family, it does not contain metal cofactors and lacks aminopeptidase activity.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.