Q13616 · CUL1_HUMAN
- ProteinCullin-1
- GeneCUL1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids776 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:22017875, PubMed:22017877, PubMed:27565346).
In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68 (PubMed:25503564, PubMed:25704143).
SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of CCNE1, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. Neddylated CUL1-RBX1 ubiquitinates p53/TP53 recruited by Cul7-RING(FBXW8) complex (PubMed:35982156).
SCF(BTRC) directs 'Lys-48'-linked ubiquitination of UBR2 in the T-cell receptor signaling pathway (PubMed:38225265).
In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68 (PubMed:25503564, PubMed:25704143).
SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of CCNE1, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. Neddylated CUL1-RBX1 ubiquitinates p53/TP53 recruited by Cul7-RING(FBXW8) complex (PubMed:35982156).
SCF(BTRC) directs 'Lys-48'-linked ubiquitination of UBR2 in the T-cell receptor signaling pathway (PubMed:38225265).
Pathway
Protein modification; protein ubiquitination.
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCullin-1
- Short namesCUL-1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ13616
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1-331 | Abolishes interaction with Cul7-RING(FBXW8) complex; does not disrupt interaction with RBX1. | ||||
Sequence: Missing |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 554 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 (large scale data), modified residue, cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000119787 | 1-776 | UniProt | Cullin-1 | |||
Sequence: MSSTRSQNPHGLKQIGLDQIWDDLRAGIQQVYTRQSMAKSRYMELYTHVYNYCTSVHQSNQARGAGVPPSKSKKGQTPGGAQFVGLELYKRLKEFLKNYLTNLLKDGEDLMDESVLKFYTQQWEDYRFSSKVLNGICAYLNRHWVRRECDEGRKGIYEIYSLALVTWRDCLFRPLNKQVTNAVLKLIEKERNGETINTRLISGVVQSYVELGLNEDDAFAKGPTLTVYKESFESQFLADTERFYTRESTEFLQQNPVTEYMKKAEARLLEEQRRVQVYLHESTQDELARKCEQVLIEKHLEIFHTEFQNLLDADKNEDLGRMYNLVSRIQDGLGELKKLLETHIHNQGLAAIEKCGEAALNDPKMYVQTVLDVHKKYNALVMSAFNNDAGFVAALDKACGRFINNNAVTKMAQSSSKSPELLARYCDSLLKKSSKNPEEAELEDTLNQVMVVFKYIEDKDVFQKFYAKMLAKRLVHQNSASDDAEASMISKLKQACGFEYTSKLQRMFQDIGVSKDLNEQFKKHLTNSEPLDLDFSIQVLSSGSWPFQQSCTFALPSELERSYQRFTAFYASRHSGRKLTWLYQLSKGELVTNCFKNRYTLQASTFQMAILLQYNTEDAYTVQQLTDSTQIKMDILAQVLQILLKSKLLVLEDENANVDEVELKPDTLIKLYLGYKNKKLRVNINVPMKTEQKQEQETTHKNIEEDRKLLIQAAIVRIMKMRKVLKHQQLLGEVLTQLSSRFKPRVPVIKKCIDILIEKEYLERVDGEKDTYSYLA | |||||||
Modified residue (large scale data) | 2 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 63 | UniProt | Omega-N-methylarginine | ||||
Sequence: R | |||||||
Cross-link | 720 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in NEDD8) | ||||
Sequence: K |
Post-translational modification
Neddylated; which enhances the ubiquitination activity of SCF and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:10597293, PubMed:10713156, PubMed:15537541, PubMed:18805092).
(Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome (PubMed:20190741).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in lung fibroblasts.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit (PubMed:10230406, PubMed:11961546, PubMed:15145941, PubMed:15531760, PubMed:16714087, PubMed:16797541, PubMed:17098746, PubMed:18203720, PubMed:20596027, PubMed:22113614, PubMed:22405651, PubMed:22748924, PubMed:23263282, PubMed:23431138, PubMed:25503564).
Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC (PubMed:22017875, PubMed:22017877).
This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF (PubMed:20596027).
Interacts with CCNF (PubMed:26818844).
Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7 (PubMed:22405651).
Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction mediates the exchange of the F-box substrate-specific subunit. Can self-associate. Interacts with FBXW8. Interacts with RNF7. Interacts with TRIM21. Interacts with COPS2. Interacts with UBE2M (PubMed:21940857).
Identified in a complex with RBX1 and GLMN (PubMed:22405651, PubMed:22748924).
Interacts with CEP68 as part of the SCF(FBXW11) complex; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT (PubMed:25503564).
Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346).
Interacts with COPS9 isoform 2 (PubMed:23776465).
Interacts with UBXN1 (PubMed:28152074).
Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (By similarity).
Interacts with NOTCH2 (PubMed:29149593).
Part of a complex that contains DCUN1D5, CUL1 and RBX1; this complex is bridged by CUL1 (PubMed:24192928).
Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:21940857, PubMed:23201271, PubMed:24192928, PubMed:25349211, PubMed:26906416, PubMed:28581483).
Interacts (via the C-terminal domain) with CUL7; the interaction seems to be mediated by FBXW8; it is likely specific to FBXW8, but not other F-box proteins (PubMed:35982156).
Interacts with UBR2, as part of SCF(BTRC) complex; the interaction mediates 'Lys-48'-linked ubiquitination of UBR2 and is regulated by DUSP22 in the T-cell receptor signaling pathway (PubMed:38225265).
Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC (PubMed:22017875, PubMed:22017877).
This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF (PubMed:20596027).
Interacts with CCNF (PubMed:26818844).
Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7 (PubMed:22405651).
Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction mediates the exchange of the F-box substrate-specific subunit. Can self-associate. Interacts with FBXW8. Interacts with RNF7. Interacts with TRIM21. Interacts with COPS2. Interacts with UBE2M (PubMed:21940857).
Identified in a complex with RBX1 and GLMN (PubMed:22405651, PubMed:22748924).
Interacts with CEP68 as part of the SCF(FBXW11) complex; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT (PubMed:25503564).
Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346).
Interacts with COPS9 isoform 2 (PubMed:23776465).
Interacts with UBXN1 (PubMed:28152074).
Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (By similarity).
Interacts with NOTCH2 (PubMed:29149593).
Part of a complex that contains DCUN1D5, CUL1 and RBX1; this complex is bridged by CUL1 (PubMed:24192928).
Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation (PubMed:21940857, PubMed:23201271, PubMed:24192928, PubMed:25349211, PubMed:26906416, PubMed:28581483).
Interacts (via the C-terminal domain) with CUL7; the interaction seems to be mediated by FBXW8; it is likely specific to FBXW8, but not other F-box proteins (PubMed:35982156).
Interacts with UBR2, as part of SCF(BTRC) complex; the interaction mediates 'Lys-48'-linked ubiquitination of UBR2 and is regulated by DUSP22 in the T-cell receptor signaling pathway (PubMed:38225265).
(Microbial infection) Interacts with Epstein-Barr virus BPLF1.
(Microbial infection) Interacts with Human adenovirus early E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBXW7) complex.
(Microbial infection) Interacts with vaccinia virus protein C9L.
(Microbial infection) Interacts with Epstein-Barr virus (EBV) tegument protein BGLF2; this interaction might facilitate CUL1 recruitment to STAT2, leading to ubiquitination and degradation of the latter.
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Sequence
- Sequence statusComplete
- Length776
- Mass (Da)89,679
- Last updated2001-08-14 v2
- Checksum6625A1FFA7799BBA
Computationally mapped potential isoform sequences
There are 10 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A590UJR3 | A0A590UJR3_HUMAN | CUL1 | 732 | ||
A0A590UK34 | A0A590UK34_HUMAN | CUL1 | 720 | ||
A0A590UJM8 | A0A590UJM8_HUMAN | CUL1 | 214 | ||
A0A590UJA0 | A0A590UJA0_HUMAN | CUL1 | 281 | ||
A0A590UJC4 | A0A590UJC4_HUMAN | CUL1 | 678 | ||
A0A590UJ97 | A0A590UJ97_HUMAN | CUL1 | 109 | ||
A0A590UJ21 | A0A590UJ21_HUMAN | CUL1 | 732 | ||
A0A590UJ50 | A0A590UJ50_HUMAN | CUL1 | 759 | ||
A0A590UJ56 | A0A590UJ56_HUMAN | CUL1 | 649 | ||
A0A590UJ59 | A0A590UJ59_HUMAN | CUL1 | 51 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 59-82 | in Ref. 1; AAC50544 | ||||
Sequence: Missing | ||||||
Sequence conflict | 726 | in Ref. 3; CAD97651 | ||||
Sequence: K → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U58087 EMBL· GenBank· DDBJ | AAC50544.1 EMBL· GenBank· DDBJ | mRNA | ||
AF062536 EMBL· GenBank· DDBJ | AAC36681.1 EMBL· GenBank· DDBJ | mRNA | ||
BX537409 EMBL· GenBank· DDBJ | CAD97651.1 EMBL· GenBank· DDBJ | mRNA | ||
AC005229 EMBL· GenBank· DDBJ | AAM49153.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471146 EMBL· GenBank· DDBJ | EAW80074.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC125119 EMBL· GenBank· DDBJ | AAI25120.1 EMBL· GenBank· DDBJ | mRNA | ||
BC125120 EMBL· GenBank· DDBJ | AAI25121.1 EMBL· GenBank· DDBJ | mRNA |