UniProtKB - Q66K89 (E4F1_HUMAN)
Protein
Transcription factor E4F1
Gene
E4F1
Organism
Homo sapiens (Human)
Status
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 + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.1 Publication EC:2.3.2.27
: protein ubiquitination Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 192 – 214 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 220 – 242 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 248 – 272 | C2H2-type 3; degeneratePROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 435 – 457 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 463 – 485 | C2H2-type 5PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 491 – 513 | C2H2-type 6PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 519 – 541 | C2H2-type 7PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 547 – 569 | C2H2-type 8PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 575 – 597 | C2H2-type 9; degeneratePROSITE-ProRule annotationAdd BLAST | 23 |
GO - Molecular functioni
- cAMP response element binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription factor activity Source: GO_Central
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: NTNU_SB
- metal ion binding Source: UniProtKB-KW
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB
- transferase activity Source: UniProtKB-KW
GO - Biological processi
- cell division Source: UniProtKB-KW
- DNA replication Source: Ensembl
- mitotic cell cycle arrest Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: GO_Central
- 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
- regulation of transcription by RNA polymerase II Source: GO_Central
- viral process Source: UniProtKB-KW
Keywordsi
Molecular function | DNA-binding, Repressor, Transferase |
Biological process | Cell cycle, Cell division, Growth regulation, Host-virus interaction, Mitosis, Transcription, Transcription regulation, Ubl conjugation pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q66K89 |
SignaLinki | Q66K89 |
SIGNORi | Q66K89 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3121, E4F1 |
MIMi | 603022, gene |
neXtProti | NX_Q66K89 |
VEuPathDBi | HostDB:ENSG00000167967.15 |
Subcellular locationi
Nucleus
Cytoplasm and Cytosol
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
Cytoskeleton
- spindle Source: Ensembl
Nucleus
- nucleoplasm Source: HPA
Other locations
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 194 | C → S: Increases DNA-binding; when associated with S-197. 1 Publication | 1 | |
Mutagenesisi | 197 | C → S: Increases DNA-binding; when associated with S-194. 1 Publication | 1 | |
Mutagenesisi | 210 | H → A: Alters DNA-binding. 1 Publication | 1 | |
Mutagenesisi | 237 | R → L: Alters DNA-binding; when associated with N-238. 1 Publication | 1 | |
Mutagenesisi | 238 | H → N: Alters DNA-binding; when associated with L-237. 1 Publication | 1 | |
Mutagenesisi | 249 | K → M: Alters DNA-binding; when associated with S-250. 1 Publication | 1 | |
Mutagenesisi | 250 | C → S: Alters DNA-binding; when associated with M-249. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 1877 |
OpenTargetsi | ENSG00000167967 |
PharmGKBi | PA27579 |
Miscellaneous databases
Pharosi | Q66K89, Tbio |
Genetic variation databases
BioMutai | E4F1 |
DMDMi | 296434488 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000324307 | 1 – 784 | Transcription factor E4F1Add BLAST | 784 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 50 | PhosphoserineCombined sources | 1 |
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 conjugationProteomic databases
EPDi | Q66K89 |
jPOSTi | Q66K89 |
MassIVEi | Q66K89 |
MaxQBi | Q66K89 |
PaxDbi | Q66K89 |
PeptideAtlasi | Q66K89 |
PRIDEi | Q66K89 |
ProteomicsDBi | 65963 |
PTM databases
iPTMneti | Q66K89 |
PhosphoSitePlusi | Q66K89 |
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
Bgeei | ENSG00000167967, Expressed in cerebellum and 111 other tissues |
ExpressionAtlasi | Q66K89, baseline and differential |
Genevisiblei | Q66K89, HS |
Organism-specific databases
HPAi | ENSG00000167967, Low tissue specificity |
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 PublicationBinary interactionsi
Hide detailsQ66K89
Protein-protein interaction databases
BioGRIDi | 108209, 91 interactors |
IntActi | Q66K89, 73 interactors |
MINTi | Q66K89 |
STRINGi | 9606.ENSP00000301727 |
Miscellaneous databases
RNActi | Q66K89, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 41 – 85 | Required for ubiquitin ligase activityAdd BLAST | 45 | |
Regioni | 184 – 263 | Mediates dimerization, DNA-binding, transcription repression of CCNA2 and interaction with HMGA21 PublicationAdd BLAST | 80 | |
Regioni | 369 – 566 | Mediates interaction with CDKN2AAdd BLAST | 198 | |
Regioni | 435 – 599 | Interaction with BMI11 PublicationAdd BLAST | 165 | |
Regioni | 521 – 580 | Mediates interaction with TP53Add BLAST | 60 | |
Regioni | 575 – 597 | Mediates interaction with RASSF11 PublicationAdd BLAST | 23 |
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 192 – 214 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 220 – 242 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 248 – 272 | C2H2-type 3; degeneratePROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 435 – 457 | C2H2-type 4PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 463 – 485 | C2H2-type 5PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 491 – 513 | C2H2-type 6PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 519 – 541 | C2H2-type 7PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 547 – 569 | C2H2-type 8PROSITE-ProRule annotationAdd BLAST | 23 | |
Zinc fingeri | 575 – 597 | C2H2-type 9; degeneratePROSITE-ProRule annotationAdd BLAST | 23 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG1721, Eukaryota |
GeneTreei | ENSGT00840000129970 |
InParanoidi | Q66K89 |
OMAi | MITHSSK |
OrthoDBi | 1318335at2759 |
PhylomeDBi | Q66K89 |
TreeFami | TF315387 |
Family and domain databases
InterProi | View protein in InterPro IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
Pfami | View protein in Pfam PF00096, zf-C2H2, 5 hits |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 10 hits |
SUPFAMi | SSF57667, SSF57667, 5 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 7 hits PS50157, ZINC_FINGER_C2H2_2, 9 hits |
(1+)i Sequence
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
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BUJ7 | H3BUJ7_HUMAN | Transcription factor E4F1 | E4F1 | 654 | Annotation score: | ||
H3BSL4 | H3BSL4_HUMAN | Transcription factor E4F1 | E4F1 | 607 | Annotation score: | ||
H3BN24 | H3BN24_HUMAN | Transcription factor E4F1 | E4F1 | 272 | Annotation score: | ||
H3BQZ4 | H3BQZ4_HUMAN | Transcription factor E4F1 | E4F1 | 208 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 4 | A → E in AAD09139 (PubMed:9121437).Curated | 1 | |
Sequence conflicti | 363 – 364 | SE → RK in AAD09139 (PubMed:9121437).Curated | 2 | |
Sequence conflicti | 425 | A → V in BAF83018 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 480 – 481 | KH → TD in AAD09139 (PubMed:9121437).Curated | 2 | |
Sequence conflicti | 544 | E → D in BAF83018 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 681 – 682 | QA → PR in AAD09139 (PubMed:9121437).Curated | 2 | |
Sequence conflicti | 704 – 705 | EA → RG in AAD09139 (PubMed:9121437).Curated | 2 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_060270 | 167 | R → H4 PublicationsCorresponds to variant dbSNP:rs26839Ensembl. | 1 | |
Natural variantiVAR_060271 | 355 | V → 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 |
CCDSi | CCDS32370.1 |
RefSeqi | NP_001275705.1, NM_001288776.1 NP_001275707.1, NM_001288778.1 NP_004415.3, NM_004424.4 |
Genome annotation databases
Ensembli | ENST00000301727; ENSP00000301727; ENSG00000167967 |
GeneIDi | 1877 |
KEGGi | hsa:1877 |
UCSCi | uc002cpm.5, human |
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 |
CCDSi | CCDS32370.1 |
RefSeqi | NP_001275705.1, NM_001288776.1 NP_001275707.1, NM_001288778.1 NP_004415.3, NM_004424.4 |
3D structure databases
SMRi | Q66K89 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108209, 91 interactors |
IntActi | Q66K89, 73 interactors |
MINTi | Q66K89 |
STRINGi | 9606.ENSP00000301727 |
PTM databases
iPTMneti | Q66K89 |
PhosphoSitePlusi | Q66K89 |
Genetic variation databases
BioMutai | E4F1 |
DMDMi | 296434488 |
Proteomic databases
EPDi | Q66K89 |
jPOSTi | Q66K89 |
MassIVEi | Q66K89 |
MaxQBi | Q66K89 |
PaxDbi | Q66K89 |
PeptideAtlasi | Q66K89 |
PRIDEi | Q66K89 |
ProteomicsDBi | 65963 |
Protocols and materials databases
Antibodypediai | 23652, 101 antibodies |
Genome annotation databases
Ensembli | ENST00000301727; ENSP00000301727; ENSG00000167967 |
GeneIDi | 1877 |
KEGGi | hsa:1877 |
UCSCi | uc002cpm.5, human |
Organism-specific databases
CTDi | 1877 |
DisGeNETi | 1877 |
GeneCardsi | E4F1 |
HGNCi | HGNC:3121, E4F1 |
HPAi | ENSG00000167967, Low tissue specificity |
MIMi | 603022, gene |
neXtProti | NX_Q66K89 |
OpenTargetsi | ENSG00000167967 |
PharmGKBi | PA27579 |
VEuPathDBi | HostDB:ENSG00000167967.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1721, Eukaryota |
GeneTreei | ENSGT00840000129970 |
InParanoidi | Q66K89 |
OMAi | MITHSSK |
OrthoDBi | 1318335at2759 |
PhylomeDBi | Q66K89 |
TreeFami | TF315387 |
Enzyme and pathway databases
UniPathwayi | UPA00143 |
PathwayCommonsi | Q66K89 |
SignaLinki | Q66K89 |
SIGNORi | Q66K89 |
Miscellaneous databases
BioGRID-ORCSi | 1877, 424 hits in 1024 CRISPR screens |
ChiTaRSi | E4F1, human |
GeneWikii | E4F1 |
GenomeRNAii | 1877 |
Pharosi | Q66K89, Tbio |
PROi | PR:Q66K89 |
RNActi | Q66K89, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000167967, Expressed in cerebellum and 111 other tissues |
ExpressionAtlasi | Q66K89, baseline and differential |
Genevisiblei | Q66K89, HS |
Family and domain databases
InterProi | View protein in InterPro IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
Pfami | View protein in Pfam PF00096, zf-C2H2, 5 hits |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 10 hits |
SUPFAMi | SSF57667, SSF57667, 5 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 7 hits PS50157, ZINC_FINGER_C2H2_2, 9 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | E4F1_HUMAN | |
Accessioni | Q66K89Primary (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: | April 7, 2021 | |
This is version 166 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways