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Protein

Proliferation-associated protein 2G4

Gene

PA2G4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Caution

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

GO - Molecular functioni

  • DNA binding Source: MGI
  • DNA-binding transcription factor activity Source: MGI
  • RNA binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionRepressor, Ribonucleoprotein, RNA-binding
Biological processrRNA processing, Transcription, Transcription regulation, Translation regulation

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000170515.13
HGNCiHGNC:8550 PA2G4
MIMi602145 gene
neXtProtiNX_Q9UQ80

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
Cross-linki298Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UQ80
PaxDbiQ9UQ80
PeptideAtlasiQ9UQ80
PRIDEiQ9UQ80
ProteomicsDBi85517

2D gel databases

SWISS-2DPAGEiQ9UQ80

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 Expressed in 237 organ(s), highest expression level in esophagus mucosa
CleanExiHS_PA2G4
ExpressionAtlasiQ9UQ80 baseline and differential
GenevisibleiQ9UQ80 HS

Organism-specific databases

HPAiCAB011711
CAB012428
HPA016484

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111075, 139 interactors
DIPiDIP-31275N
ELMiQ9UQ80
IntActiQ9UQ80, 62 interactors
MINTiQ9UQ80
STRINGi9606.ENSP00000302886

Structurei

Secondary structure

1394
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiHTVLLMP
OrthoDBiEOG091G0B89
PhylomeDBiQ9UQ80
TreeFamiTF300010

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR036005 Creatinase/aminopeptidase-like
IPR004545 PA2G4
IPR000994 Pept_M24
IPR018349 Pept_M24A_MAP2_BS
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00557 Peptidase_M24, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF55920 SSF55920, 2 hits
TIGRFAMsiTIGR00495 crvDNA_42K, 1 hit
PROSITEiView protein in PROSITE
PS01202 MAP_2, 1 hit

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

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VR77F8VR77_HUMAN
Proliferation-associated protein 2G...
PA2G4
284Annotation score:
F8W0A3F8W0A3_HUMAN
Proliferation-associated protein 2G...
PA2G4
187Annotation score:
F8VZ69F8VZ69_HUMAN
Proliferation-associated protein 2G...
PA2G4
64Annotation score:

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

Similar proteinsi

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, 139 interactors
DIPiDIP-31275N
ELMiQ9UQ80
IntActiQ9UQ80, 62 interactors
MINTiQ9UQ80
STRINGi9606.ENSP00000302886

Protein family/group databases

MEROPSiM24.973

PTM databases

iPTMnetiQ9UQ80
PhosphoSitePlusiQ9UQ80
SwissPalmiQ9UQ80

Polymorphism and mutation databases

BioMutaiPA2G4
DMDMi13632817

2D gel databases

SWISS-2DPAGEiQ9UQ80

Proteomic databases

EPDiQ9UQ80
PaxDbiQ9UQ80
PeptideAtlasiQ9UQ80
PRIDEiQ9UQ80
ProteomicsDBi85517

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
EuPathDBiHostDB:ENSG00000170515.13
GeneCardsiPA2G4
HGNCiHGNC:8550 PA2G4
HPAiCAB011711
CAB012428
HPA016484
MIMi602145 gene
neXtProtiNX_Q9UQ80
OpenTargetsiENSG00000170515
PharmGKBiPA32877
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2776 Eukaryota
COG0024 LUCA
GeneTreeiENSGT00530000063220
HOGENOMiHOG000168207
HOVERGENiHBG053117
InParanoidiQ9UQ80
OMAiHTVLLMP
OrthoDBiEOG091G0B89
PhylomeDBiQ9UQ80
TreeFamiTF300010

Enzyme and pathway databases

ReactomeiR-HSA-6798695 Neutrophil degranulation
SIGNORiQ9UQ80

Miscellaneous databases

ChiTaRSiPA2G4 human
EvolutionaryTraceiQ9UQ80
GeneWikiiPA2G4
GenomeRNAii5036
PROiPR:Q9UQ80
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170515 Expressed in 237 organ(s), highest expression level in esophagus mucosa
CleanExiHS_PA2G4
ExpressionAtlasiQ9UQ80 baseline and differential
GenevisibleiQ9UQ80 HS

Family and domain databases

Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR036005 Creatinase/aminopeptidase-like
IPR004545 PA2G4
IPR000994 Pept_M24
IPR018349 Pept_M24A_MAP2_BS
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00557 Peptidase_M24, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF55920 SSF55920, 2 hits
TIGRFAMsiTIGR00495 crvDNA_42K, 1 hit
PROSITEiView protein in PROSITE
PS01202 MAP_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPA2G4_HUMAN
AccessioniPrimary (citable) accession number: Q9UQ80
Secondary accession number(s): O43846, Q9UM59
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 189 of the entry and version 3 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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