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Protein

Transcription factor E4F1

Gene

E4F1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication

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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Repressor, Transferase
Biological processCell cycle, Cell division, Growth regulation, Host-virus interaction, Mitosis, Transcription, Transcription regulation, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ66K89
SIGNORiQ66K89
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor E4F1 (EC:2.3.2.271 Publication)
Alternative name(s):
E4F transcription factor 1
Putative E3 ubiquitin-protein ligase E4F1
RING-type E3 ubiquitin transferase E4F1Curated
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

EuPathDBiHostDB:ENSG00000167967.15
HGNCiHGNC:3121 E4F1
MIMi603022 gene
neXtProtiNX_Q66K89

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

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
ProteomicsDBi65963

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 Expressed in 90 organ(s), highest expression level in cerebellum
CleanExiHS_E4F1
ExpressionAtlasiQ66K89 baseline and differential
GenevisibleiQ66K89 HS

Organism-specific databases

HPAiHPA052042
HPA071325

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 RASSF1.10 Publications
(Microbial infection) Interacts with HBV protein X.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi108209, 89 interactors
IntActiQ66K89, 13 interactors
MINTiQ66K89
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

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
KOiK22401
OMAiSGHQIIV
OrthoDBiEOG091G03X5
PhylomeDBiQ66K89
TreeFamiTF315387

Family and domain databases

InterProiView protein in InterPro
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF00096 zf-C2H2, 4 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 10 hits
SUPFAMiSSF57667 SSF57667, 5 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 7 hits
PS50157 ZINC_FINGER_C2H2_2, 9 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BUJ7H3BUJ7_HUMAN
Transcription factor E4F1
E4F1
654Annotation score:
H3BSL4H3BSL4_HUMAN
Transcription factor E4F1
E4F1
607Annotation score:
H3BN24H3BN24_HUMAN
Transcription factor E4F1
E4F1
272Annotation score:
H3BQZ4H3BQZ4_HUMAN
Transcription factor E4F1
E4F1
208Annotation score:

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 → H4 PublicationsCorresponds to variant dbSNP:rs26839Ensembl.1
Natural variantiVAR_060271355V → I. Corresponds to variant dbSNP:rs59784157Ensembl.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

Similar proteinsi

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, 89 interactors
IntActiQ66K89, 13 interactors
MINTiQ66K89
STRINGi9606.ENSP00000301727

PTM databases

iPTMnetiQ66K89
PhosphoSitePlusiQ66K89

Polymorphism and mutation databases

DMDMi296434488

Proteomic databases

EPDiQ66K89
MaxQBiQ66K89
PaxDbiQ66K89
PeptideAtlasiQ66K89
PRIDEiQ66K89
ProteomicsDBi65963

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1877
DisGeNETi1877
EuPathDBiHostDB:ENSG00000167967.15
GeneCardsiE4F1
HGNCiHGNC:3121 E4F1
HPAiHPA052042
HPA071325
MIMi603022 gene
neXtProtiNX_Q66K89
OpenTargetsiENSG00000167967
PharmGKBiPA27579
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1721 Eukaryota
COG5048 LUCA
GeneTreeiENSGT00840000129970
HOGENOMiHOG000168447
HOVERGENiHBG052707
InParanoidiQ66K89
KOiK22401
OMAiSGHQIIV
OrthoDBiEOG091G03X5
PhylomeDBiQ66K89
TreeFamiTF315387

Enzyme and pathway databases

UniPathwayi
UPA00143

SignaLinkiQ66K89
SIGNORiQ66K89

Miscellaneous databases

GeneWikiiE4F1
GenomeRNAii1877
PROiPR:Q66K89
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167967 Expressed in 90 organ(s), highest expression level in cerebellum
CleanExiHS_E4F1
ExpressionAtlasiQ66K89 baseline and differential
GenevisibleiQ66K89 HS

Family and domain databases

InterProiView protein in InterPro
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
PfamiView protein in Pfam
PF00096 zf-C2H2, 4 hits
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 10 hits
SUPFAMiSSF57667 SSF57667, 5 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 7 hits
PS50157 ZINC_FINGER_C2H2_2, 9 hits
ProtoNetiSearch...

Entry informationi

Entry nameiE4F1_HUMAN
AccessioniPrimary (citable) accession number: Q66K89
Secondary accession number(s): A8K2R4, O00146
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 150 of the entry and version 2 of the sequence. See 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
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Main funding by: National Institutes of Health

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