Human Gene CUL1 (ENST00000409469.5) from GENCODE V44
Description: 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. 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 is inhibited by the association of the deneddylated cullin subunit with 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(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 cyclin E, 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(FBXO11) 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(Cyclin F) directs ubiquitination of CP110 (By similarity). (from UniProt Q13616) Gencode Transcript: ENST00000409469.5 Gencode Gene: ENSG00000055130.18 Transcript (Including UTRs) Position: hg38 chr7:148,697,914-148,800,582 Size: 102,669 Total Exon Count: 22 Strand: + Coding Region Position: hg38 chr7:148,730,123-148,800,582 Size: 70,460 Coding Exon Count: 21
ID:CUL1_HUMAN DESCRIPTION: RecName: Full=Cullin-1; Short=CUL-1; 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. 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 is inhibited by the association of the deneddylated cullin subunit with 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(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 cyclin E, 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(FBXO11) 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(Cyclin F) directs ubiquitination of CP110 (By similarity). PATHWAY: Protein modification; protein ubiquitination. 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. 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(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. Interacts with RNF7. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction negatively regulates the association with SKP1 in the SCF complex. Interacts with COPS2. Can self-associate. Interacts with FBXW8. Interacts with CUL7; the interaction seems to be mediated by FBXW8. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2 (By similarity). Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts with TRIM21. Interacts with Epstein-Barr virus BPLF1. 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(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF. Interacts with human adenovirus early E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBW7) complex. Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. INTERACTION: Q86VP6:CAND1; NbExp=18; IntAct=EBI-359390, EBI-456077; P49427:CDC34; NbExp=3; IntAct=EBI-359390, EBI-975634; Q00987:MDM2; NbExp=3; IntAct=EBI-359390, EBI-389668; P62877:RBX1; NbExp=12; IntAct=EBI-359390, EBI-398523; P63208:SKP1; NbExp=6; IntAct=EBI-359390, EBI-307486; Q13309:SKP2; NbExp=8; IntAct=EBI-359390, EBI-456291; TISSUE SPECIFICITY: Expressed in lung fibroblasts. PTM: Neddylated; which enhances the ubiquitination activity of SCF. Deneddylated via its interaction with the COP9 signalosome (CSN) complex. Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome. SIMILARITY: Belongs to the cullin family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q13616
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_skp2e2fPathway - E2F1 Destruction Pathway h_fbw7Pathway - Cyclin E Destruction Pathway h_eradPathway - ER¿associated degradation (ERAD) Pathway h_p27Pathway - Regulation of p27 Phosphorylation during Cell Cycle Progression
Reactome (by CSHL, EBI, and GO)
Protein Q13616 (Reactome details) participates in the following event(s):
R-HSA-5691131 CANDI binds CUL1 R-HSA-5691167 CUL1, SKP1, FBXL5 bind R-HSA-8854052 Formation of the SCF-FBXL7 complex R-HSA-174209 Phosphorylated Emi1 binds the beta-TrCP in the SCF complex R-HSA-209125 SCF Beta-TrCP complex binds to NFKB p50:p65: phospho IKBA complex R-HSA-1370500 PRLR binds SCF beta-TrCP complex R-HSA-2130279 Association of beta-catenin with the RBX1:SCF(beta-TrCP1) ubiquitin ligase complex R-HSA-5607723 SCF-beta-TRCP binds p-7S-p100 in active NIK:p-S176,180-IKKA dimer:p-7S-p100:RELB R-HSA-5691176 NEDD8 binds CUL1 (in SKP1:CUL1:FXBL5) R-HSA-8853496 SCF:FBXL7 binds AURKA R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex R-HSA-983147 Release of E3 from polyubiquitinated substrate R-HSA-187545 Association of Cks1 with SCF(Skp2) complex R-HSA-1912385 Phosphorylated NICD1 binds FBXW7 R-NUL-2064853 FBXW7 binds phosphorylated NICD1 R-HSA-1852623 Ubiquitination of NICD1 by FBWX7 R-NUL-2064883 FBXW7 mediates ubiquitination of phosphorylated NICD1 R-HSA-9008478 FBXW7 binds RUNX2 and GSK3B R-HSA-8939688 SCF(SKP2) complex binds RUNX2 R-HSA-8939706 SCF(SKP2) polyubiquitinates RUNX2 R-HSA-174159 Ubiquitination of Emi1 by SCF-beta-TrCP R-HSA-1168642 SCF with beta-TrCP1 or beta-TrCP2 binds NF-kappaB:phospho-IkB R-HSA-3000339 Phosphorylated BORA binds SCF-beta-TrCp1/2 R-HSA-5684248 SCF betaTrCP1,2 binds p-NFkB p105:TPL2:ABIN2 R-HSA-3000335 SCF-beta-TrCp1/2 ubiquitinates phosphorylated BORA R-HSA-5684250 SCF betaTrCP ubiquitinates NFKB p105 within p-S927, S932-NFkB p105:TPL2:ABIN2 R-HSA-209063 Beta-TrCP ubiquitinates NFKB p50:p65:phospho IKBA complex R-HSA-2130286 Multi-ubiquitination of phospho-beta-catenin by RBX1:SCF(beta-TrCP1) R-HSA-5610742 SCF(beta-TrCP) ubiquitinates p-GLI1 R-HSA-5610745 SCF(beta-TrCP) ubiquitinates p-GLI2 R-HSA-5610746 SCF(beta-TrCP) ubiquitinates p-GLI3 R-HSA-8952620 NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex R-HSA-8956200 MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex R-HSA-8955241 CAND1 binds cytosolic CRL E3 ubiquitin ligases R-HSA-8854041 SCF-FBXL7 ubiquitinates AURKA R-HSA-8854051 SCF-FBXL18 ubiquitinates FBXL7 R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2 R-HSA-187552 Binding of phospho-p27/p21:Cdk2:Cyclin E/A to the SCF(Skp2):Cks1 complex R-HSA-1363328 Phosphorylated p130 (RBL2) binds SCF(Skp2):Cks1 complex R-HSA-1363331 Ubiquitination of p130 (RBL2) by SCF (Skp2) R-HSA-9008479 FBXW7 polyubiquitinates RUNX2 R-HSA-68946 Phosphorylated Orc1 is ubiquitinated while still associated with chromatin R-HSA-8952618 AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex R-HSA-8955289 COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes R-HSA-8956040 COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes R-HSA-5691108 SKP1:FBXL5:CUL1:NEDD8 ubiquitinylates IREB2 R-HSA-187575 Ubiquitination of phospho-p27/p21 R-HSA-917937 Iron uptake and transport R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1 R-HSA-9020702 Interleukin-1 signaling R-HSA-1170546 Prolactin receptor signaling R-HSA-195253 Degradation of beta-catenin by the destruction complex R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling R-HSA-5676590 NIK-->noncanonical NF-kB signaling R-HSA-202424 Downstream TCR signaling R-HSA-2871837 FCERI mediated NF-kB activation R-HSA-5607764 CLEC7A (Dectin-1) signaling R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation R-HSA-382551 Transport of small molecules R-HSA-69275 G2/M Transition R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21 R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-2644607 Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling R-HSA-8939902 Regulation of RUNX2 expression and activity R-HSA-1169091 Activation of NF-kappaB in B cells R-HSA-2565942 Regulation of PLK1 Activity at G2/M Transition R-HSA-5684264 MAP3K8 (TPL2)-dependent MAPK1/3 activation R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase R-HSA-400253 Circadian Clock R-HSA-446652 Interleukin-1 family signaling R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-195721 Signaling by WNT R-HSA-5610780 Degradation of GLI1 by the proteasome R-HSA-5610783 Degradation of GLI2 by the proteasome R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome R-HSA-8951664 Neddylation R-HSA-5668541 TNFR2 non-canonical NF-kB pathway R-HSA-202403 TCR signaling R-HSA-2454202 Fc epsilon receptor (FCERI) signaling R-HSA-5621481 C-type lectin receptors (CLRs) R-HSA-983169 Class I MHC mediated antigen processing & presentation R-HSA-453274 Mitotic G2-G2/M phases R-HSA-69231 Cyclin D associated events in G1 R-HSA-69202 Cyclin E associated events during G1/S transition R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry R-HSA-1980143 Signaling by NOTCH1 R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2644605 FBXW7 Mutants and NOTCH1 in Cancer R-HSA-8878166 Transcriptional regulation by RUNX2 R-HSA-68949 Orc1 removal from chromatin R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR) R-HSA-450294 MAP kinase activation R-HSA-174143 APC/C-mediated degradation of cell cycle proteins R-HSA-449147 Signaling by Interleukins R-HSA-168256 Immune System R-HSA-162582 Signal Transduction R-HSA-5610787 Hedgehog 'off' state R-HSA-597592 Post-translational protein modification R-HSA-1280218 Adaptive Immune System R-HSA-168249 Innate Immune System R-HSA-69278 Cell Cycle (Mitotic) R-HSA-69236 G1 Phase R-HSA-69206 G1/S Transition R-HSA-69242 S Phase R-HSA-157118 Signaling by NOTCH R-HSA-2644603 Signaling by NOTCH1 in Cancer R-HSA-212436 Generic Transcription Pathway R-HSA-69052 Switching of origins to a post-replicative state R-HSA-983705 Signaling by the B Cell Receptor (BCR) R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade R-HSA-448424 Interleukin-17 signaling R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975871 MyD88 cascade initiated on plasma membrane R-HSA-453276 Regulation of mitotic cell cycle R-HSA-5358351 Signaling by Hedgehog R-HSA-392499 Metabolism of proteins R-HSA-1640170 Cell Cycle R-HSA-453279 Mitotic G1-G1/S phases R-HSA-5663202 Diseases of signal transduction R-HSA-73857 RNA Polymerase II Transcription R-HSA-69239 Synthesis of DNA R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade R-HSA-168898 Toll-Like Receptors Cascades R-HSA-166166 MyD88-independent TLR4 cascade R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade R-HSA-1643685 Disease R-HSA-74160 Gene expression (Transcription) R-HSA-69306 DNA Replication R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade
US Server
