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Q8CCE9 (E4F1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Transcription factor E4F1

EC=6.3.2.-
Alternative name(s):
E4F transcription factor 1
Putative E3 ubiquitin-protein ligase E4F1
Transcription factor E4F
Transcription factor phi AP3
p120E4F
Gene names
Name:E4f1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length783 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function as a transcriptional repressor. May also function as a ubiquitin ligase mediating ubiquitination of chromatin-associated TP53. Functions in cell survival and proliferation through control of the cell cycle. Functions in the p53 and pRB tumor suppressor pathways and regulates the cyclin CCNA2 transcription. Ref.4 Ref.6 Ref.8 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Homodimer; binds DNA as a dimer By similarity. Forms a complex with CDKN2A and TP53. Interacts with HDAC1, HMGA2 and RASSF1 By similarity. Interactions with TP53, RB1, ANP32A and probably BMI1 and FHL2 regulate E4F1 activity. Ref.6 Ref.7 Ref.9

Subcellular location

Nucleusnucleoplasm. Cytoplasm By similarity. Note: A small fraction is detected in the cytoplasm By similarity. Excluded from the nucleolus where it is targeted upon CDKN2A overexpression. Localizes to the mitotic spindle during embryogenesis. Ref.4 Ref.8

Tissue specificity

Ubiquitously expressed. Ref.4 Ref.5

Developmental stage

Continuously expressed during embryogenesis. Ref.5

Post-translational modification

Phosphorylated; phosphorylation is cell cycle-dependent and regulates DNA-binding activity and function. Ref.4

May be sumoylated by UBE2I upon interaction with CDKN2A By similarity.

Disruption phenotype

Death before E7.5 probably at the peri-implantation stage. Blastocysts display defects in mitotic progression and chromosomal segregation and increased apoptosis. Ref.8

Sequence similarities

Contains 9 C2H2-type zinc fingers.

Sequence caution

The sequence AAF22563.1 differs from that shown. Reason: Frameshift at positions 230 and 235.

The sequence AAH71228.1 differs from that shown. Reason: Frameshift at position 94.

The sequence BAE25748.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAA54188.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processCell cycle
Cell division
Growth regulation
Mitosis
Transcription
Transcription regulation
Ubl conjugation pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
Zinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionLigase
Repressor
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from mutant phenotype Ref.8. Source: MGI

mitotic nuclear division

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein ubiquitination

Inferred from electronic annotation. Source: UniProtKB-UniPathway

regulation of cell cycle process

Inferred from direct assay PubMed 14645522. Source: UniProtKB

regulation of growth

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of mitotic cell cycle, embryonic

Inferred from mutant phenotype Ref.8. Source: MGI

regulation of transcription, DNA-templated

Traceable author statement Ref.8. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay Ref.8. Source: MGI

spindle

Inferred from direct assay Ref.8. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay Ref.8. Source: MGI

cAMP response element binding

Inferred from electronic annotation. Source: Ensembl

ligase activity

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.9. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Anp32aO353812EBI-7450874,EBI-643140

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8CCE9-1)

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.
Isoform 2 (identifier: Q8CCE9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     667-684: DSHIMKVVQQIVHQAGAG → RVWVRDGRITGLLGSPSG
     685-783: Missing.
Isoform 3 (identifier: Q8CCE9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     422-422: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q8CCE9-4)

The sequence of this isoform differs from the canonical sequence as follows:
     458-458: A → VWQGLPQSLP...AWHTQPAPAH
     459-783: Missing.
Note: No experimental confirmation available.
Isoform 5 (identifier: Q8CCE9-5)

The sequence of this isoform differs from the canonical sequence as follows:
     244-274: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 783783Transcription factor E4F1
PRO_0000324308

Regions

Zinc finger193 – 21523C2H2-type 1
Zinc finger221 – 24323C2H2-type 2
Zinc finger249 – 27325C2H2-type 3; degenerate
Zinc finger434 – 45623C2H2-type 4
Zinc finger462 – 48423C2H2-type 5
Zinc finger490 – 51223C2H2-type 6
Zinc finger518 – 54023C2H2-type 7
Zinc finger546 – 56823C2H2-type 8
Zinc finger574 – 59623C2H2-type 9; degenerate
Region40 – 8445Required for ubiquitin ligase activity By similarity
Region185 – 26480Mediates dimerization, DNA-binding, transcription repression of CCNA2 and interaction with HMGA2 By similarity
Region368 – 565198Mediates interaction with CDKN2A By similarity
Region434 – 598165Interaction with BMI1 By similarity
Region520 – 57960Mediates interaction with TP53 By similarity
Region574 – 59623Mediates interaction with RASSF1 By similarity

Amino acid modifications

Modified residue491Phosphoserine By similarity

Natural variations

Alternative sequence244 – 27431Missing in isoform 5.
VSP_032192
Alternative sequence4221Missing in isoform 3.
VSP_032193
Alternative sequence4581A → VWQGLPQSLPAQEAPGGARA RAPLPLWRLWEALQDHRSCA GPPACSLRREAFPLSPVRQA LQNQECPASTLPDTSGRKAP RVPVLQPRLPGEGLSGAACE APHRRETFQVLQVWPWLRGA WHTQPAPAH in isoform 4.
VSP_032194
Alternative sequence459 – 783325Missing in isoform 4.
VSP_032195
Alternative sequence667 – 68418DSHIM…QAGAG → RVWVRDGRITGLLGSPSG in isoform 2.
VSP_032196
Alternative sequence685 – 78399Missing in isoform 2.
VSP_032197

Experimental info

Sequence conflict131H → D in BAE25748. Ref.2
Sequence conflict181R → G in AAF22563. Ref.1
Sequence conflict181R → G in BAE25748. Ref.2
Sequence conflict181R → G in AAH46459. Ref.3
Sequence conflict181R → G in AAH71228. Ref.3
Sequence conflict301V → VA in AAF22563. Ref.1
Sequence conflict301V → VA in BAE25748. Ref.2
Sequence conflict621C → F in BAE25748. Ref.2
Sequence conflict1391V → A in CAA54188. Ref.4
Sequence conflict1481I → V in CAA54188. Ref.4
Sequence conflict1581V → G in AAF22563. Ref.1
Sequence conflict1581V → G in BAE25748. Ref.2
Sequence conflict1581V → G in AAH46459. Ref.3
Sequence conflict1581V → G in AAH71228. Ref.3
Sequence conflict1581V → G in CAA54188. Ref.4
Sequence conflict224 – 2252KL → NF in AAF22563. Ref.1
Sequence conflict2811S → N in AAF22563. Ref.1
Sequence conflict2811S → N in BAE25748. Ref.2
Sequence conflict3801V → L in AAF22563. Ref.1
Sequence conflict3901A → V in AAF22563. Ref.1
Sequence conflict395 – 4006PPSGSS → LPFGST in AAF22563. Ref.1
Sequence conflict4121P → L in AAF22563. Ref.1
Sequence conflict479 – 4802KH → ND in CAA54188. Ref.4
Sequence conflict585 – 5862EH → DD in CAA54188. Ref.4
Sequence conflict6301E → Q in AAF22563. Ref.1
Sequence conflict6301E → Q in BAE25748. Ref.2
Sequence conflict6301E → Q in AAH46459. Ref.3
Sequence conflict6301E → Q in CAA54188. Ref.4
Sequence conflict7051T → A in AAF22563. Ref.1
Sequence conflict7051T → A in BAE25748. Ref.2
Sequence conflict7051T → A in CAA54188. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 18, 2008. Version 2.
Checksum: 59E47F7A64A224A4

FASTA78384,296
        10         20         30         40         50         60 
MEGAMAVRVT AAHTAEARAE AGREAGEGGV AAAAALSSGG FLGLPAPFSE EDEDDVHRCG 

        70         80         90        100        110        120 
RCQVEFTALE DFVQHKIQKT CHRAPQEALP TTPAATALLD QEVVPTAAEG GPDEPITVAH 

       130        140        150        160        170        180 
IVVEATSLAE DISHAPDLVG SGHIKEVIVA AEAEPGDVEM AEAPGSPNHQ ELGLLGEGEQ 

       190        200        210        220        230        240 
AHVKLLVNKE GRYVCMLCHK TFKTGSILKA HMVTHSSRKD HECKLCGASF RTKGSLIRHH 

       250        260        270        280        290        300 
RRHTDERPYK CAKCGKSFRE SGALTRHLKS LTPCTEKIRF SISKDTAVGK EEVPAGSSAS 

       310        320        330        340        350        360 
TVGTVTSSVA GDPMETSPVI HLVTDAKGTV IHEVHVQMQE LPLGMKALTP ESPDSEELPC 

       370        380        390        400        410        420 
SSENSRENLL HQAMQNSGIV LERVAGEESA LEPAPPSGSS PQCLGDGSPE LPLLKVEQIE 

       430        440        450        460        470        480 
TQVASEAATV PRTHPCPQCS ETFPTAATLE AHKRGHIAPR PFTCTQCGKA FPKAYLLKKH 

       490        500        510        520        530        540 
QEVHVHERRF RCGDCGKLYK TIAHVRGHRR VHSDERPFPC PQCGKRYKTK NAQQVHFRTH 

       550        560        570        580        590        600 
LEEKPHVCQF CSRGFREKGS LVRHVRHHTG EKPFKCYKCG RGFAEHGTLN RHLRTKGGCL 

       610        620        630        640        650        660 
LEVEELLVSE ESPSAAATVL AEDPHTVLVE FSSVVADTQE YIIEATADDT ETSEATEIIE 

       670        680        690        700        710        720 
GTQTEVDSHI MKVVQQIVHQ AGAGHQIIVQ NVTMDQETAL GSEATAADTI TIATPESLTE 

       730        740        750        760        770        780 
QVAMTLASAI SEGTVLTARA GPNSTEQATV TMVSSEDIEI LEHGGELVIA SPEGQLEVQT 


VIV 

« Hide

Isoform 2 [UniParc].

Checksum: 62B9E2973ACA07C3
Show »

FASTA68474,060
Isoform 3 [UniParc].

Checksum: F0CEA4AC61FE5BDA
Show »

FASTA78284,168
Isoform 4 [UniParc].

Checksum: 03DE21745C393119
Show »

FASTA58662,553
Isoform 5 [UniParc].

Checksum: BC7A27C32B98E325
Show »

FASTA75280,830

References

« Hide 'large scale' references
[1]"Repression of the murine Il-1 beta expression by the murine analog of E4F transcription factor."
Lebedeva T.V., Singh A.K.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-783 (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Embryonic testis.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 79-783 (ISOFORM 5).
Strain: C57BL/6, FVB/N and NMRI.
Tissue: Brain and Mammary tumor.
[4]"Repression of adenovirus E1A enhancer activity by a novel zinc finger-containing DNA-binding protein related to the GLI-Kruppel protein."
Fognani C., Della Valle G., Babiss L.E.
EMBO J. 12:4985-4992(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 65-783 (ISOFORM 1), FUNCTION, DNA-BINDING, SUBCELLULAR LOCATION, PHOSPHORYLATION, TISSUE SPECIFICITY.
Strain: BALB/c.
Tissue: Liver.
[5]"Chromosomal location and tissue expression of the gene encoding the adenovirus E1A-regulated transcription factor E4F in humans and mice."
Rooney R.J., Daniels R.R., Jenkins N.A., Gilbert D.J., Rothammer K., Morris S.W., Higgs D.R., Copeland N.G.
Mamm. Genome 9:320-323(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[6]"p53 is involved in the p120E4F-mediated growth arrest."
Sandy P., Gostissa M., Fogal V., Cecco L.D., Szalay K., Rooney R.J., Schneider C., Del Sal G.
Oncogene 19:188-199(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TP53.
[7]"pRB binds to and modulates the transrepressing activity of the E1A-regulated transcription factor p120E4F."
Fajas L., Paul C., Zugasti O., Le Cam L., Polanowska J., Fabbrizio E., Medema R., Vignais M.-L., Sardet C.
Proc. Natl. Acad. Sci. U.S.A. 97:7738-7743(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RB1.
[8]"The E4F protein is required for mitotic progression during embryonic cell cycles."
Le Cam L., Lacroix M., Ciemerych M.A., Sardet C., Sicinski P.
Mol. Cell. Biol. 24:6467-6475(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION.
[9]"The role of LANP and ataxin 1 in E4F-mediated transcriptional repression."
Cvetanovic M., Rooney R.J., Garcia J.J., Toporovskaya N., Zoghbi H.Y., Opal P.
EMBO Rep. 8:671-677(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ANP32A.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF126967 mRNA. Translation: AAF22563.1. Frameshift.
AK033285 mRNA. Translation: BAC28222.1.
AK144176 mRNA. Translation: BAE25748.1. Different initiation.
BC046459 mRNA. Translation: AAH46459.1.
BC057011 mRNA. Translation: AAH57011.1.
BC071228 mRNA. Translation: AAH71228.1. Frameshift.
X76858 mRNA. Translation: CAA54188.1. Different initiation.
CCDSCCDS28481.1. [Q8CCE9-3]
PIRS41688.
RefSeqNP_031919.2. NM_007893.3. [Q8CCE9-3]
XP_006523657.1. XM_006523594.1. [Q8CCE9-1]
UniGeneMm.163132.

3D structure databases

ProteinModelPortalQ8CCE9.
SMRQ8CCE9. Positions 182-271, 443-634.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199353. 2 interactions.
IntActQ8CCE9. 1 interaction.
MINTMINT-4979074.

PTM databases

PhosphoSiteQ8CCE9.

Proteomic databases

PRIDEQ8CCE9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000056032; ENSMUSP00000062344; ENSMUSG00000024137. [Q8CCE9-3]
GeneID13560.
KEGGmmu:13560.
UCSCuc008avy.1. mouse. [Q8CCE9-3]
uc008awa.1. mouse. [Q8CCE9-1]
uc008awb.1. mouse. [Q8CCE9-2]
uc012ami.1. mouse. [Q8CCE9-5]

Organism-specific databases

CTD1877.
MGIMGI:109530. E4f1.

Phylogenomic databases

eggNOGCOG5048.
GeneTreeENSGT00390000006768.
HOVERGENHBG052707.
InParanoidQ8CCE9.
OMACQFCSRG.
OrthoDBEOG761BT6.
PhylomeDBQ8CCE9.
TreeFamTF315387.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

BgeeQ8CCE9.
CleanExMM_E4F1.
GenevestigatorQ8CCE9.

Family and domain databases

Gene3D3.30.160.60. 8 hits.
InterProIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamPF00096. zf-C2H2. 2 hits.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 10 hits.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 7 hits.
PS50157. ZINC_FINGER_C2H2_2. 9 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio284182.
PROQ8CCE9.
SOURCESearch...

Entry information

Entry nameE4F1_MOUSE
AccessionPrimary (citable) accession number: Q8CCE9
Secondary accession number(s): Q05BH7 expand/collapse secondary AC list , Q3UNJ9, Q62065, Q6IR08, Q6PGI1, Q9QY56
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: March 18, 2008
Last modified: July 9, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

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