Q01094 · E2F1_HUMAN
- ProteinTranscription factor E2F1
- GeneE2F1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids437 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication (PubMed:10675335, PubMed:12717439, PubMed:17050006, PubMed:17704056, PubMed:18625225, PubMed:28992046).
The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase (PubMed:10675335, PubMed:12717439, PubMed:17704056).
E2F1 binds preferentially RB1 in a cell-cycle dependent manner (PubMed:10675335, PubMed:12717439, PubMed:17704056).
It can mediate both cell proliferation and TP53/p53-dependent apoptosis (PubMed:8170954).
Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters (PubMed:20176812).
Directly activates transcription of PEG10 (PubMed:17050006, PubMed:18625225, PubMed:28992046).
Positively regulates transcription of RRP1B (PubMed:20040599).
The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase (PubMed:10675335, PubMed:12717439, PubMed:17704056).
E2F1 binds preferentially RB1 in a cell-cycle dependent manner (PubMed:10675335, PubMed:12717439, PubMed:17704056).
It can mediate both cell proliferation and TP53/p53-dependent apoptosis (PubMed:8170954).
Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters (PubMed:20176812).
Directly activates transcription of PEG10 (PubMed:17050006, PubMed:18625225, PubMed:28992046).
Positively regulates transcription of RRP1B (PubMed:20040599).
Activity regulation
BIRC2/c-IAP1 stimulates its transcriptional activity.
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 110-194 | |||||
Sequence: GRGRHPGKGVKSPGEKSRYETSLNLTTKRFLELLSHSADGVVDLNWAAEVLKVQKRRIYDITNVLEGIQLIAKKSKNHIQWLGSH |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTranscription factor E2F1
- Short namesE2F-1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ01094
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 117 | Abolishes acetylation; when associated with R-120 and R-125. | ||||
Sequence: K → R | ||||||
Mutagenesis | 120 | Abolishes acetylation; when associated with R-117 and R-125. | ||||
Sequence: K → R | ||||||
Mutagenesis | 125 | Abolishes acetylation; when associated with R-117 and R-120. | ||||
Sequence: K → R | ||||||
Mutagenesis | 132 | Abolishes interaction with and repression of CEBPA and inhibition of adipogenesis. | ||||
Sequence: L → E | ||||||
Mutagenesis | 185 | Abrogates methylation by SETD7. Loss of interaction with L3MBTL3. Loss of ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_048907 | 200 | in dbSNP:rs35385772 | |||
Sequence: G → S | ||||||
Natural variant | VAR_013607 | 252 | in dbSNP:rs3213172 | |||
Sequence: R → H | ||||||
Natural variant | VAR_013608 | 276 | in dbSNP:rs3213173 | |||
Sequence: V → M | ||||||
Natural variant | VAR_013609 | 311 | in dbSNP:rs3213174 | |||
Sequence: T → N | ||||||
Mutagenesis | 364 | Abrogates in vitro phosphorylation by CHEK2 and CHEK2-dependent stabilization of E2F1 upon DNA damage. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_013610 | 393 | in dbSNP:rs3213176 | |||
Sequence: G → S | ||||||
Mutagenesis | 403 | Decreased phosphorylation by GSK3B, leading to abolished interaction with USP11 and subsequent deubiquitination. | ||||
Sequence: S → A | ||||||
Mutagenesis | 411 | No retinoblastoma protein binding. No effect on interaction with and repression of CEBPA. | ||||
Sequence: Y → C | ||||||
Mutagenesis | 433 | Decreased phosphorylation by GSK3B. | ||||
Sequence: T → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 416 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000219461 | 1-437 | UniProt | Transcription factor E2F1 | |||
Sequence: MALAGAPAGGPCAPALEALLGAGALRLLDSSQIVIISAAQDASAPPAPTGPAAPAAGPCDPDLLLFATPQAPRPTPSAPRPALGRPPVKRRLDLETDHQYLAESSGPARGRGRHPGKGVKSPGEKSRYETSLNLTTKRFLELLSHSADGVVDLNWAAEVLKVQKRRIYDITNVLEGIQLIAKKSKNHIQWLGSHTTVGVGGRLEGLTQDLRQLQESEQQLDHLMNICTTQLRLLSEDTDSQRLAYVTCQDLRSIADPAEQMVMVIKAPPETQLQAVDSSENFQISLKSKQGPIDVFLCPEETVGGISPGKTPSQEVTSEEENRATDSATIVSPPPSSPPSSLTTDPSQSLLSLEQEPLLSRMGSLRAPVDEDRLSPLVAADSLLEHVREDFSGLLPEEFISLSPPHEALDYHFGLEEGEGIRDLFDCDFGDLTPLDF | |||||||
Modified residue | 117 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 120 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 125 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 185 | UniProt | N6-methyllysine; by SETD7 | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 307 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 364 | UniProt | Phosphoserine; by CHEK2 | ||||
Sequence: S | |||||||
Modified residue | 375 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 375 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 403 | UniProt | Phosphoserine; by GSK3-beta | ||||
Sequence: S | |||||||
Modified residue | 433 | UniProt | Phosphothreonine; by GSK3-beta | ||||
Sequence: T |
Post-translational modification
Phosphorylated by CDK2 and cyclin A-CDK2 in the S-phase (PubMed:12717439, PubMed:7838523).
Phosphorylation at Ser-364 by CHEK2 stabilizes E2F1 upon DNA damage and regulates its effect on transcription and apoptosis (PubMed:12717439).
Phosphorylation at Ser-403 by GSK3B promotes interaction with USP11, leading to its deubiquitination and stabilization (PubMed:28992046).
Phosphorylation at Ser-364 by CHEK2 stabilizes E2F1 upon DNA damage and regulates its effect on transcription and apoptosis (PubMed:12717439).
Phosphorylation at Ser-403 by GSK3B promotes interaction with USP11, leading to its deubiquitination and stabilization (PubMed:28992046).
Ubiquitinated via 'Lys-63'-linked ubiquitin, leading to its degradation (PubMed:28992046).
Deubiquitinated by USP11 following phosphorylation by GSK3B, promoting its stability (PubMed:28992046).
Deubiquitinated by USP11 following phosphorylation by GSK3B, promoting its stability (PubMed:28992046).
Acetylation stimulates DNA-binding. Enhanced under stress conditions such as DNA damage and inhibited by retinoblastoma protein RB1. Regulated by KAP1/TRIM28 which recruits HDAC1 to E2F1 resulting in deacetylation. Acetylated by P/CAF/KAT2B.
Methylation at Lys-185 by SETD7 promotes E2F1 ubiquitin-dependent proteasomal degradation.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Component of the DRTF1/E2F transcription factor complex. Forms heterodimers with DP family members. The E2F1 complex binds specifically hypophosphorylated RB1, the interaction represses E2F1-driven transcription (PubMed:8336704).
During the cell cycle, RB1 becomes phosphorylated in mid-to-late G1 phase, detaches from the DRTF1/E2F complex, rendering E2F transcriptionally active. Viral oncoproteins, notably E1A, T-antigen and HPV E7, are capable of sequestering RB1, thus releasing the active complex. Interacts with TRRAP, which probably mediates its interaction with histone acetyltransferase complexes, leading to transcription activation. Binds TOPBP1 and EAPP. Interacts with ARID3A. Interacts with TRIM28; the interaction inhibits E2F1 acetylation through recruiting HDAC1 and represses its transcriptional activity. Interaction with KAT2B; the interaction acetylates E2F1 enhancing its DNA-binding and transcriptional activity. Interacts with BIRC2/c-IAP1 (via BIR domains). The complex TFDP1:E2F1 interacts with CEBPA; the interaction prevents CEBPA binding to target genes promoters and represses its transcriptional activity (PubMed:20176812).
Interacts with RRP1B (PubMed:20040599).
Interacts with HCFC1 (PubMed:23629655).
Interacts with KMT2E; the interaction is probably indirect and is mediated via HCFC1 (PubMed:23629655).
Interacts with DCAF5 and L3MBTL3; the interaction requires methylation at Lys-185 and is necessary to target E2F1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex (PubMed:29691401).
During the cell cycle, RB1 becomes phosphorylated in mid-to-late G1 phase, detaches from the DRTF1/E2F complex, rendering E2F transcriptionally active. Viral oncoproteins, notably E1A, T-antigen and HPV E7, are capable of sequestering RB1, thus releasing the active complex. Interacts with TRRAP, which probably mediates its interaction with histone acetyltransferase complexes, leading to transcription activation. Binds TOPBP1 and EAPP. Interacts with ARID3A. Interacts with TRIM28; the interaction inhibits E2F1 acetylation through recruiting HDAC1 and represses its transcriptional activity. Interaction with KAT2B; the interaction acetylates E2F1 enhancing its DNA-binding and transcriptional activity. Interacts with BIRC2/c-IAP1 (via BIR domains). The complex TFDP1:E2F1 interacts with CEBPA; the interaction prevents CEBPA binding to target genes promoters and represses its transcriptional activity (PubMed:20176812).
Interacts with RRP1B (PubMed:20040599).
Interacts with HCFC1 (PubMed:23629655).
Interacts with KMT2E; the interaction is probably indirect and is mediated via HCFC1 (PubMed:23629655).
Interacts with DCAF5 and L3MBTL3; the interaction requires methylation at Lys-185 and is necessary to target E2F1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex (PubMed:29691401).
(Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL123.
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 42-87 | Disordered | ||||
Sequence: ASAPPAPTGPAAPAAGPCDPDLLLFATPQAPRPTPSAPRPALGRPP | ||||||
Region | 67-108 | Cyclin A:CDK2 binding | ||||
Sequence: ATPQAPRPTPSAPRPALGRPPVKRRLDLETDHQYLAESSGPA | ||||||
Region | 89-191 | Interaction with BIRC2/c-IAP1 | ||||
Sequence: KRRLDLETDHQYLAESSGPARGRGRHPGKGVKSPGEKSRYETSLNLTTKRFLELLSHSADGVVDLNWAAEVLKVQKRRIYDITNVLEGIQLIAKKSKNHIQWL | ||||||
Region | 101-128 | Disordered | ||||
Sequence: LAESSGPARGRGRHPGKGVKSPGEKSRY | ||||||
Region | 153-174 | Leucine-zipper | ||||
Sequence: LNWAAEVLKVQKRRIYDITNVL | ||||||
Motif | 158-194 | DEF box | ||||
Sequence: EVLKVQKRRIYDITNVLEGIQLIAKKSKNHIQWLGSH | ||||||
Region | 192-382 | Required for interaction with TRIM28 | ||||
Sequence: GSHTTVGVGGRLEGLTQDLRQLQESEQQLDHLMNICTTQLRLLSEDTDSQRLAYVTCQDLRSIADPAEQMVMVIKAPPETQLQAVDSSENFQISLKSKQGPIDVFLCPEETVGGISPGKTPSQEVTSEEENRATDSATIVSPPPSSPPSSLTTDPSQSLLSLEQEPLLSRMGSLRAPVDEDRLSPLVAADS | ||||||
Region | 195-284 | Dimerization | ||||
Sequence: TTVGVGGRLEGLTQDLRQLQESEQQLDHLMNICTTQLRLLSEDTDSQRLAYVTCQDLRSIADPAEQMVMVIKAPPETQLQAVDSSENFQI | ||||||
Region | 300-349 | Disordered | ||||
Sequence: EETVGGISPGKTPSQEVTSEEENRATDSATIVSPPPSSPPSSLTTDPSQS | ||||||
Region | 368-437 | Transactivation | ||||
Sequence: PVDEDRLSPLVAADSLLEHVREDFSGLLPEEFISLSPPHEALDYHFGLEEGEGIRDLFDCDFGDLTPLDF | ||||||
Region | 409-426 | RB1 binding | ||||
Sequence: LDYHFGLEEGEGIRDLFD |
Sequence similarities
Belongs to the E2F/DP family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length437
- Mass (Da)46,920
- Last updated1993-07-01 v1
- Checksum003B3F654F0C60DF
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 89-111 | in Ref. 8; AAD14150 | ||||
Sequence: KRRLDLETDHQYLAESSGPARGR → RTPGTPRRQRRLCPPRRPGRAPC | ||||||
Sequence conflict | 313 | in Ref. 4; AAC50719 | ||||
Sequence: S → Y | ||||||
Sequence conflict | 322 | in Ref. 4; AAC50719 | ||||
Sequence: N → T | ||||||
Sequence conflict | 329 | in Ref. 4; AAC50719 | ||||
Sequence: T → N |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M96577 EMBL· GenBank· DDBJ | AAA35782.1 EMBL· GenBank· DDBJ | mRNA | ||
U47677 EMBL· GenBank· DDBJ | AAC50719.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U47675 EMBL· GenBank· DDBJ | AAC50719.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U47676 EMBL· GenBank· DDBJ | AAC50719.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
S49592 EMBL· GenBank· DDBJ | AAB24289.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AF516106 EMBL· GenBank· DDBJ | AAM47604.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL121906 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC050369 EMBL· GenBank· DDBJ | AAH50369.1 EMBL· GenBank· DDBJ | mRNA | ||
BC058902 EMBL· GenBank· DDBJ | AAH58902.1 EMBL· GenBank· DDBJ | mRNA | ||
S74230 EMBL· GenBank· DDBJ | AAD14150.1 EMBL· GenBank· DDBJ | Genomic DNA |