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Protein

Forkhead box protein O4

Gene

Foxo4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

BioGridi2076801 interactor.
CORUMiQ9WVH3
IntActiQ9WVH3 3 interactors.
MINTiQ9WVH3
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
GeneTreeiENSGT00910000144016
HOGENOMiHOG000251635
HOVERGENiHBG057789
InParanoidiQ9WVH3
KOiK12358
OMAiENLECDM
OrthoDBiEOG091G06K3
PhylomeDBiQ9WVH3
TreeFamiTF315583

Family and domain databases

CDDicd00059 FH, 1 hit
Gene3Di1.10.10.101 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: March 28, 2018
This is version 150 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