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Protein

Transcription factor E4F1

Gene

E4F1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.
Identified as a cellular target of the adenoviral oncoprotein E1A, it is required for both transcriptional activation and repression of viral genes.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri192 – 214C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri220 – 242C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri248 – 272C2H2-type 3; degeneratePROSITE-ProRule annotationAdd BLAST25
Zinc fingeri435 – 457C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri463 – 485C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri491 – 513C2H2-type 6PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri519 – 541C2H2-type 7PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri547 – 569C2H2-type 8PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri575 – 597C2H2-type 9; degeneratePROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

  • cAMP response element binding Source: UniProtKB
  • DNA binding Source: ProtInc
  • ligase activity Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: NTNU_SB
  • transcription coactivator activity Source: ProtInc
  • transcription corepressor activity Source: ProtInc
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cell proliferation Source: ProtInc
  • DNA replication Source: Ensembl
  • mitotic cell cycle arrest Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of cell cycle process Source: UniProtKB
  • regulation of growth Source: UniProtKB-KW
  • regulation of mitotic cell cycle, embryonic Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Ligase, Repressor

Keywords - Biological processi

Cell cycle, Cell division, Growth regulation, Host-virus interaction, Mitosis, Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ66K89.
SIGNORiQ66K89.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor E4F1 (EC:6.3.2.-)
Alternative name(s):
E4F transcription factor 1
Putative E3 ubiquitin-protein ligase E4F1
Transcription factor E4F
p120E4F
p50E4F
Gene namesi
Name:E4F1
Synonyms:E4F
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:3121. E4F1.

Subcellular locationi

  • Nucleusnucleoplasm
  • Cytoplasm

  • Note: A small fraction is detected in the cytoplasm. Excluded from the nucleolus where it is targeted upon CDKN2A overexpression. Localizes to the mitotic spindle during embryogenesis (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi194C → S: Increases DNA-binding; when associated with S-197. 1 Publication1
Mutagenesisi197C → S: Increases DNA-binding; when associated with S-194. 1 Publication1
Mutagenesisi210H → A: Alters DNA-binding. 1 Publication1
Mutagenesisi237R → L: Alters DNA-binding; when associated with N-238. 1 Publication1
Mutagenesisi238H → N: Alters DNA-binding; when associated with L-237. 1 Publication1
Mutagenesisi249K → M: Alters DNA-binding; when associated with S-250. 1 Publication1
Mutagenesisi250C → S: Alters DNA-binding; when associated with M-249. 1 Publication1

Organism-specific databases

DisGeNETi1877.
OpenTargetsiENSG00000167967.
PharmGKBiPA27579.

Polymorphism and mutation databases

DMDMi296434488.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003243071 – 784Transcription factor E4F1Add BLAST784

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50PhosphoserineCombined sources1

Post-translational modificationi

Proteolytic cleavage produces a 50 kDa N-terminal peptide (p50E4F) which has a DNA-binding activity and activates transcription in presence of the adenoviral E1A protein. The major full length protein (p120E4F) functions as a repressor of transcription.1 Publication
Phosphorylated; p120E4F and p50E4F are both phosphorylated. Phosphorylation is cell cycle-dependent and differentially regulates DNA-binding activity and function of both forms.2 Publications
May be sumoylated by UBE2I upon interaction with CDKN2A.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ66K89.
MaxQBiQ66K89.
PaxDbiQ66K89.
PeptideAtlasiQ66K89.
PRIDEiQ66K89.

PTM databases

iPTMnetiQ66K89.
PhosphoSitePlusiQ66K89.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Developmental stagei

Expressed in a variety of fetal tissues.1 Publication

Inductioni

Up-regulated by estrogen.1 Publication

Gene expression databases

BgeeiENSG00000167967.
CleanExiHS_E4F1.
ExpressionAtlasiQ66K89. baseline and differential.
GenevisibleiQ66K89. HS.

Organism-specific databases

HPAiHPA052042.

Interactioni

Subunit structurei

Homodimer; binds DNA as a dimer. Forms a complex with CDKN2A and TP53. Interactions with TP53, RB1, ANP32A, BMI1 and FHL2 regulate E4F1 activity. Interacts with HDAC1, HMGA2 and RASSF1. Interacts with HBV protein X.11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
8Q647704EBI-1227043,EBI-8642971From a different organism.
ANP32AP396873EBI-1227043,EBI-359234
HDAC1Q135473EBI-1227043,EBI-301834
HDAC1Q6IT962EBI-1227043,EBI-6979193
lnx2bA4VCF73EBI-1227043,EBI-6979266From a different organism.
RASSF1Q9NS23-27EBI-1227043,EBI-438698
tcf7l1aQ9YHE82EBI-1227043,EBI-6979298From a different organism.

Protein-protein interaction databases

BioGridi108209. 76 interactors.
IntActiQ66K89. 12 interactors.
MINTiMINT-137139.
STRINGi9606.ENSP00000301727.

Structurei

3D structure databases

ProteinModelPortaliQ66K89.
SMRiQ66K89.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni41 – 85Required for ubiquitin ligase activityAdd BLAST45
Regioni184 – 263Mediates dimerization, DNA-binding, transcription repression of CCNA2 and interaction with HMGA21 PublicationAdd BLAST80
Regioni369 – 566Mediates interaction with CDKN2AAdd BLAST198
Regioni435 – 599Interaction with BMI11 PublicationAdd BLAST165
Regioni521 – 580Mediates interaction with TP53Add BLAST60
Regioni575 – 597Mediates interaction with RASSF11 PublicationAdd BLAST23

Sequence similaritiesi

Contains 9 C2H2-type zinc fingers.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri192 – 214C2H2-type 1PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri220 – 242C2H2-type 2PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri248 – 272C2H2-type 3; degeneratePROSITE-ProRule annotationAdd BLAST25
Zinc fingeri435 – 457C2H2-type 4PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri463 – 485C2H2-type 5PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri491 – 513C2H2-type 6PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri519 – 541C2H2-type 7PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri547 – 569C2H2-type 8PROSITE-ProRule annotationAdd BLAST23
Zinc fingeri575 – 597C2H2-type 9; degeneratePROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00840000129970.
HOGENOMiHOG000168447.
HOVERGENiHBG052707.
InParanoidiQ66K89.
OMAiSGHQIIV.
OrthoDBiEOG091G03X5.
PhylomeDBiQ66K89.
TreeFamiTF315387.

Family and domain databases

Gene3Di3.30.160.60. 9 hits.
InterProiIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF13912. zf-C2H2_6. 4 hits.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 10 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 7 hits.
PS50157. ZINC_FINGER_C2H2_2. 9 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q66K89-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGAMAVRVT AAHTAEAQAE AGREAGEGAV AAVAAALAPS GFLGLPAPFS
60 70 80 90 100
EEDEDDVHRC GRCQAEFTAL EDFVQHKIQK ACQRAPPEAL PATPATTALL
110 120 130 140 150
GQEVVPAAPG PEEPITVAHI VVEAASLAAD ISHASDLVGG GHIKEVIVAA
160 170 180 190 200
EAELGDGEMA EAPGSPRQQG LGLAGEGEQA QVKLLVNKDG RYVCALCHKT
210 220 230 240 250
FKTGSILKAH MVTHSSRKDH ECKLCGASFR TKGSLIRHHR RHTDERPYKC
260 270 280 290 300
SKCGKSFRES GALTRHLKSL TPCTEKIRFS VSKDVVVSKE DARAGSGAGA
310 320 330 340 350
AGLGTATSSV TGEPIETSPV IHLVTDAKGT VIHEVHVQMQ ELSLGMKALA
360 370 380 390 400
PEPPVSQELP CSSEGSRENL LHQAMQNSGI VLERAAGEEG ALEPAPAAGS
410 420 430 440 450
SPQPLAVAAP QLPVLEVQPL ETQVASEASA VPRTHPCPQC SETFPTAATL
460 470 480 490 500
EAHKRGHTGP RPFACAQCGK AFPKAYLLKK HQEVHVRERR FRCGDCGKLY
510 520 530 540 550
KTIAHVRGHR RVHSDERPYP CPKCGKRYKT KNAQQVHFRT HLEEKPHVCQ
560 570 580 590 600
FCSRGFREKG SLVRHVRHHT GEKPFKCYKC GRGFAEHGTL NRHLRTKGGC
610 620 630 640 650
LLEVEELLVS EDSPAAATTV LTEDPHTVLV EFSSVVADTQ EYIIEATADD
660 670 680 690 700
AETSEATEII EGTQTEVDSH IMKVVQQIVH QASAGHQIIV QNVTMDEETA
710 720 730 740 750
LGPEAAAADT ITIATPESLT EQVAMTLASA ISEGTVLAAR AGTSGTEQAT
760 770 780
VTMVSSEDIE ILEHAGELVI ASPEGQLEVQ TVIV
Length:784
Mass (Da):83,496
Last modified:May 18, 2010 - v2
Checksum:i60F6E711F2748FD8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti4A → E in AAD09139 (PubMed:9121437).Curated1
Sequence conflicti363 – 364SE → RK in AAD09139 (PubMed:9121437).Curated2
Sequence conflicti425A → V in BAF83018 (PubMed:14702039).Curated1
Sequence conflicti480 – 481KH → TD in AAD09139 (PubMed:9121437).Curated2
Sequence conflicti544E → D in BAF83018 (PubMed:14702039).Curated1
Sequence conflicti681 – 682QA → PR in AAD09139 (PubMed:9121437).Curated2
Sequence conflicti704 – 705EA → RG in AAD09139 (PubMed:9121437).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_060270167R → H.4 PublicationsCorresponds to variant rs26839dbSNPEnsembl.1
Natural variantiVAR_060271355V → I.Corresponds to variant rs59784157dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87269 mRNA. Translation: AAD09139.1.
AK290329 mRNA. Translation: BAF83018.1.
AC009065 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85532.1.
BC080524 mRNA. Translation: AAH80524.1.
CCDSiCCDS32370.1.
RefSeqiNP_001275705.1. NM_001288776.1.
NP_001275707.1. NM_001288778.1.
NP_004415.3. NM_004424.4.
UniGeneiHs.513268.

Genome annotation databases

EnsembliENST00000301727; ENSP00000301727; ENSG00000167967.
GeneIDi1877.
KEGGihsa:1877.
UCSCiuc002cpm.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87269 mRNA. Translation: AAD09139.1.
AK290329 mRNA. Translation: BAF83018.1.
AC009065 Genomic DNA. No translation available.
CH471112 Genomic DNA. Translation: EAW85532.1.
BC080524 mRNA. Translation: AAH80524.1.
CCDSiCCDS32370.1.
RefSeqiNP_001275705.1. NM_001288776.1.
NP_001275707.1. NM_001288778.1.
NP_004415.3. NM_004424.4.
UniGeneiHs.513268.

3D structure databases

ProteinModelPortaliQ66K89.
SMRiQ66K89.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108209. 76 interactors.
IntActiQ66K89. 12 interactors.
MINTiMINT-137139.
STRINGi9606.ENSP00000301727.

PTM databases

iPTMnetiQ66K89.
PhosphoSitePlusiQ66K89.

Polymorphism and mutation databases

DMDMi296434488.

Proteomic databases

EPDiQ66K89.
MaxQBiQ66K89.
PaxDbiQ66K89.
PeptideAtlasiQ66K89.
PRIDEiQ66K89.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000301727; ENSP00000301727; ENSG00000167967.
GeneIDi1877.
KEGGihsa:1877.
UCSCiuc002cpm.5. human.

Organism-specific databases

CTDi1877.
DisGeNETi1877.
GeneCardsiE4F1.
HGNCiHGNC:3121. E4F1.
HPAiHPA052042.
MIMi603022. gene.
neXtProtiNX_Q66K89.
OpenTargetsiENSG00000167967.
PharmGKBiPA27579.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1721. Eukaryota.
COG5048. LUCA.
GeneTreeiENSGT00840000129970.
HOGENOMiHOG000168447.
HOVERGENiHBG052707.
InParanoidiQ66K89.
OMAiSGHQIIV.
OrthoDBiEOG091G03X5.
PhylomeDBiQ66K89.
TreeFamiTF315387.

Enzyme and pathway databases

UniPathwayiUPA00143.
SignaLinkiQ66K89.
SIGNORiQ66K89.

Miscellaneous databases

GeneWikiiE4F1.
GenomeRNAii1877.
PROiQ66K89.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167967.
CleanExiHS_E4F1.
ExpressionAtlasiQ66K89. baseline and differential.
GenevisibleiQ66K89. HS.

Family and domain databases

Gene3Di3.30.160.60. 9 hits.
InterProiIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
PfamiPF13912. zf-C2H2_6. 4 hits.
[Graphical view]
SMARTiSM00355. ZnF_C2H2. 10 hits.
[Graphical view]
PROSITEiPS00028. ZINC_FINGER_C2H2_1. 7 hits.
PS50157. ZINC_FINGER_C2H2_2. 9 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiE4F1_HUMAN
AccessioniPrimary (citable) accession number: Q66K89
Secondary accession number(s): A8K2R4, O00146
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 132 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. 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.