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Protein

Forkhead box protein O4

Gene

Foxo4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity (By similarity). Represses smooth muscle cell differentiation by inhibiting the transcriptional coactivator activity of myocardin.By similarity1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi100 – 188Fork-headPROSITE-ProRule annotationAdd BLAST89

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Developmental protein, DNA-binding
Biological processCell cycle, Differentiation, Myogenesis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-198693. AKT phosphorylates targets in the nucleus.
R-MMU-5689880. Ub-specific processing proteases.

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein O4
Alternative name(s):
Afxh
Fork head domain transcription factor AFX1
Gene namesi
Name:Foxo4
Synonyms:Afx, Afx1, Fkhr3, Mllt7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1891915. Foxo4.

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000918761 – 505Forkhead box protein O4Add BLAST505

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei32Phosphothreonine; by PKB/AKT1By similarity1
Modified residuei197Phosphoserine; by PKB/AKT1By similarity1
Modified residuei262Phosphoserine; by PKB/AKT1By similarity1

Post-translational modificationi

Acetylation by CREBBP/CBP is induced by oxidative stress and inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity (By similarity).By similarity
Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK (By similarity).By similarity
Monoubiquitinated; monoubiquitination is induced by oxidative stress and reduced by deacetylase inhibitors; results in its relocalization to the nucleus and its increased transcriptional activity. Deubiquitinated by USP7; deubiquitination is induced by oxidative stress; enhances its interaction with USP7 and consequently, deubiquitination; increases its translocation to the cytoplasm and inhibits its transcriptional activity. Hydrogene-peroxide-induced ubiquitination and USP7-mediated deubiquitination have no major effect on its protein stability (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9WVH3.
PaxDbiQ9WVH3.
PRIDEiQ9WVH3.

PTM databases

iPTMnetiQ9WVH3.
PhosphoSitePlusiQ9WVH3.

Expressioni

Tissue specificityi

Strongly expressed in brown adipose tissue and weakly in white adipose tissue (at protein level). Expressed in skeletal muscle.2 Publications

Inductioni

By artery ligation in proliferating neointimal smooth muscle cells.1 Publication

Gene expression databases

BgeeiENSMUSG00000042903.
CleanExiMM_FOXO4.
ExpressionAtlasiQ9WVH3. baseline and differential.
GenevisibleiQ9WVH3. MM.

Interactioni

Subunit structurei

Interacts with CREBBP/CBP, MYOCD, SIRT1, SRF and YWHAZ. Acetylated by CREBBP/CBP and deacetylated by SIRT1. Binding of YWHAZ inhibits DNA-binding. Interacts with USP7; the interaction is enhanced in presence of hydrogen peroxide and occurs independently of TP53. Interacts with NLK, and this inhibits monoubiquitination and transcriptional activity (By similarity). Interacts with FOXK1; the interaction inhibits MEF2C transactivation activity (PubMed:22956541).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
OgtP565582EBI-4567305,EBI-7614183From Rattus norvegicus.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi207680. 1 interactor.
CORUMiQ9WVH3.
IntActiQ9WVH3. 3 interactors.
MINTiMINT-4095287.
STRINGi10090.ENSMUSP00000059420.

Structurei

3D structure databases

ProteinModelPortaliQ9WVH3.
SMRiQ9WVH3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni97 – 215Required for interaction with FOXK11 PublicationAdd BLAST119

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00790000123003.
HOGENOMiHOG000251635.
HOVERGENiHBG057789.
InParanoidiQ9WVH3.
KOiK12358.
OMAiENLECDM.
OrthoDBiEOG091G06K3.
PhylomeDBiQ9WVH3.
TreeFamiTF315583.

Family and domain databases

CDDicd00059. FH. 1 hit.
Gene3Di1.10.10.10. 1 hit.
InterProiView protein in InterPro
IPR001766. Fork_head_dom.
IPR032067. FOXO-TAD.
IPR030456. TF_fork_head_CS_2.
IPR036388. WH-like_DNA-bd_sf.
IPR036390. WH_DNA-bd_sf.
PfamiView protein in Pfam
PF00250. Forkhead. 1 hit.
PF16676. FOXO-TAD. 1 hit.
PRINTSiPR00053. FORKHEAD.
SMARTiView protein in SMART
SM00339. FH. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiView protein in PROSITE
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9WVH3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDPENKKSAT GAAAILDLDP DFEPQSRPRS CTWPLPRPDL ATEPHEPSEV
60 70 80 90 100
EPSLGQKVPT EGHSEPILLP SRLPEPAGGP QPGILGAVTG PRKGGSRRNA
110 120 130 140 150
WGNQSYAELI SQAIESAPEK RLTLAQIYEW MVRTVPYFKD KGDSNSSAGW
160 170 180 190 200
KNSIRHNLSL HSKFIKVHNE ATGKSSWWML NPDGGKGGKA PRRRAASMDS
210 220 230 240 250
SSKLLRGRSK GPKKKPSVLP APPEGATPRS PLGHFAKWSS SPCPRNREEA
260 270 280 290 300
DVWTTFRPRS SSNASTVSTR LSPMRPESEV LAEEEMPASA SSYAGGVPPT
310 320 330 340 350
LSEDLELLDG LNLASPHSLL SRSGLSGFSL QHPGLAGPLH SYGASLFGPI
360 370 380 390 400
DGSLSAGEGC FSSSQSLEAL LTSDTPPPPA DVLMTQVDPI LSQAPTLLLL
410 420 430 440 450
GGMPSSSKLG TGVSLCPTPL EGPGPSNLVP NLSVMAPPPV MAGAPIPKVL
460 470 480 490 500
GTPVLASPTE DSSHDRMPQD LDLDMYMENL ECDMDNIISD LMDGEGLDFN

FEPDP
Length:505
Mass (Da):53,649
Last modified:November 1, 1999 - v1
Checksum:iABB99B54807C7CE5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF114260 mRNA. Translation: AAD42108.1.
AB032770 mRNA. Translation: BAA86199.1.
CCDSiCCDS41077.1.
RefSeqiNP_061259.1. NM_018789.2.
UniGeneiMm.240299.

Genome annotation databases

EnsembliENSMUST00000062000; ENSMUSP00000059420; ENSMUSG00000042903.
GeneIDi54601.
KEGGimmu:54601.
UCSCiuc009twz.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiFOXO4_MOUSE
AccessioniPrimary (citable) accession number: Q9WVH3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 1, 1999
Last modified: October 25, 2017
This is version 147 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot