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Protein

Proliferation-associated protein 2G4

Gene

Pa2g4

Organism
Mus musculus (Mouse)
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 (By similarity). Mediates cap-independent translation of specific viral IRESs (internal ribosomal entry site). Together with PTBP1 is required for the translation initiation on the foot-and-mouth disease virus (FMDV) IRES. Regulates cell proliferation, differentiation, and survival. Isoform 1 suppresses apoptosis whereas isoform 2 promotes cell differentiation (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

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

ReactomeiR-MMU-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiM24.973.

Names & Taxonomyi

Protein namesi
Recommended name:
Proliferation-associated protein 2G4
Alternative name(s):
IRES-specific cellular trans-acting factor 45 kDa
Short name:
ITAF45
Mpp1
Proliferation-associated protein 1
Protein p38-2G4
Gene namesi
Name:Pa2g4
Synonyms:Ebp1, Plfap
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:894684. Pa2g4.

Subcellular locationi

Isoform 1 :
  • Cytoplasm By similarity
  • Nucleusnucleolus By similarity

  • Note: Phosphorylation at Ser-361 by PKC/PRKCD regulates its nucleolar localization.By similarity
Isoform 2 :
  • Cytoplasm 1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi65 – 72KKEKEMKK → SSSSSSSS: No effect on RNA-binding. 1 Publication8

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001489902 – 394Proliferation-associated protein 2G4Add BLAST393

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei2PhosphoserineCombined sources1
Modified residuei335PhosphoserineBy similarity1
Modified residuei361Phosphoserine; by PKC/PRKCDBy similarity1
Modified residuei386PhosphothreonineBy similarity1

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.By similarity
Isoform 2 is polyubiquitinated, leading to proteasomal degradation and phosphorylation by PKC/PRKCD enhances polyubiquitination.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP50580.
PaxDbiP50580.
PeptideAtlasiP50580.
PRIDEiP50580.

PTM databases

iPTMnetiP50580.
PhosphoSitePlusiP50580.
SwissPalmiP50580.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Developmental stagei

Expressed in proliferating cells. Observed between G1 and mid S phase, decrease toward the end of S phase, and disappear at the S/G2 transition.1 Publication

Inductioni

By mitogens.1 Publication

Gene expression databases

BgeeiENSMUSG00000025364.
CleanExiMM_PA2G4.
ExpressionAtlasiP50580. baseline and differential.
GenevisibleiP50580. MM.

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 nucleolin/NCL. 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 (By similarity). Interacts with AKT1 (By similarity). Isoform 1 and isoform 2 interact with RNF20 (By similarity). Isoform 2 interacts with HUWE1. Interacts with DNAJC21 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202246. 4 interactors.
IntActiP50580. 7 interactors.
MINTiMINT-1857756.
STRINGi10090.ENSMUSP00000026425.

Structurei

Secondary structure

1394
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi15 – 36Combined sources22
Helixi45 – 60Combined sources16
Beta strandi72 – 82Combined sources11
Beta strandi85 – 87Combined sources3
Beta strandi93 – 95Combined sources3
Beta strandi105 – 114Combined sources10
Beta strandi117 – 126Combined sources10
Helixi138 – 156Combined sources19
Helixi163 – 176Combined sources14
Beta strandi186 – 189Combined sources4
Beta strandi194 – 196Combined sources3
Beta strandi198 – 204Combined sources7
Helixi207 – 212Combined sources6
Beta strandi223 – 233Combined sources11
Beta strandi246 – 249Combined sources4
Helixi260 – 272Combined sources13
Turni273 – 275Combined sources3
Helixi280 – 282Combined sources3
Helixi286 – 298Combined sources13
Beta strandi301 – 305Combined sources5
Beta strandi316 – 326Combined sources11
Beta strandi329 – 332Combined sources4
Helixi340 – 342Combined sources3
Helixi352 – 357Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V6CX-ray2.50A9-360[»]
ProteinModelPortaliP50580.
SMRiP50580.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50580.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 48Necessary for nucleolar localizationBy similarityAdd BLAST47
Regioni46 – 54RNA-bindingBy similarity9
Regioni301 – 394Necessary for nucleolar localizationBy similarityAdd BLAST94
Regioni361 – 375Interaction with RNA1 PublicationAdd BLAST15

Sequence similaritiesi

Belongs to the peptidase M24 family.Curated

Phylogenomic databases

eggNOGiKOG2776. Eukaryota.
COG0024. LUCA.
GeneTreeiENSGT00530000063220.
HOGENOMiHOG000168207.
HOVERGENiHBG053117.
InParanoidiP50580.
OMAiTHEVYAM.
OrthoDBiEOG091G0B89.
PhylomeDBiP50580.
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: P50580-1) [UniParc]FASTAAdd to basket

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 VAHTFVIGVA 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 KKKASKTVEN ATSGETLEEN GAGD
Length:394
Mass (Da):43,699
Last modified:January 23, 2007 - v3
Checksum:iABCD169F064261EB
GO
Isoform 2Curated (identifier: P50580-2) [UniParc]FASTAAdd to basket

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

Show »
Length:340
Mass (Da):37,971
Checksum:i0512D357D48D910F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti279T → A no nucleotide entry (PubMed:10950867).Curated1
Sequence conflicti311K → R no nucleotide entry (PubMed:10950867).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0573261 – 54Missing in isoform 2. 1 PublicationAdd BLAST54

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X84789 mRNA. Translation: CAA59260.1.
U43918 mRNA. Translation: AAB60513.1.
BC046532 mRNA. Translation: AAH46532.1.
CCDSiCCDS24282.1. [P50580-1]
PIRiI48702. S54181.
RefSeqiNP_035249.1. NM_011119.3. [P50580-1]
UniGeneiMm.4742.

Genome annotation databases

EnsembliENSMUST00000026425; ENSMUSP00000026425; ENSMUSG00000025364. [P50580-1]
GeneIDi18813.
KEGGimmu:18813.
UCSCiuc007hnl.1. mouse. [P50580-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X84789 mRNA. Translation: CAA59260.1.
U43918 mRNA. Translation: AAB60513.1.
BC046532 mRNA. Translation: AAH46532.1.
CCDSiCCDS24282.1. [P50580-1]
PIRiI48702. S54181.
RefSeqiNP_035249.1. NM_011119.3. [P50580-1]
UniGeneiMm.4742.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2V6CX-ray2.50A9-360[»]
ProteinModelPortaliP50580.
SMRiP50580.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202246. 4 interactors.
IntActiP50580. 7 interactors.
MINTiMINT-1857756.
STRINGi10090.ENSMUSP00000026425.

Protein family/group databases

MEROPSiM24.973.

PTM databases

iPTMnetiP50580.
PhosphoSitePlusiP50580.
SwissPalmiP50580.

Proteomic databases

EPDiP50580.
PaxDbiP50580.
PeptideAtlasiP50580.
PRIDEiP50580.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026425; ENSMUSP00000026425; ENSMUSG00000025364. [P50580-1]
GeneIDi18813.
KEGGimmu:18813.
UCSCiuc007hnl.1. mouse. [P50580-1]

Organism-specific databases

CTDi5036.
MGIiMGI:894684. Pa2g4.

Phylogenomic databases

eggNOGiKOG2776. Eukaryota.
COG0024. LUCA.
GeneTreeiENSGT00530000063220.
HOGENOMiHOG000168207.
HOVERGENiHBG053117.
InParanoidiP50580.
OMAiTHEVYAM.
OrthoDBiEOG091G0B89.
PhylomeDBiP50580.
TreeFamiTF300010.

Enzyme and pathway databases

ReactomeiR-MMU-6798695. Neutrophil degranulation.

Miscellaneous databases

ChiTaRSiPa2g4. mouse.
EvolutionaryTraceiP50580.
PROiP50580.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025364.
CleanExiMM_PA2G4.
ExpressionAtlasiP50580. baseline and differential.
GenevisibleiP50580. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: P50580
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 150 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

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, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. 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.