Q96GG9 · DCNL1_HUMAN
- ProteinDCN1-like protein 1
- GeneDCUN1D1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids259 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Part of an E3 ubiquitin ligase complex for neddylation (PubMed:18826954).
Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes (PubMed:19617556, PubMed:23201271, PubMed:23401859, PubMed:26906416).
Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity (PubMed:25349211, PubMed:28581483).
Acts also as an oncogene facilitating malignant transformation and carcinogenic progression (By similarity).
Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes (PubMed:19617556, PubMed:23201271, PubMed:23401859, PubMed:26906416).
Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates. Involved in the release of inhibitory effets of CAND1 on cullin-RING ligase E3 complex assembly and activity (PubMed:25349211, PubMed:28581483).
Acts also as an oncogene facilitating malignant transformation and carcinogenic progression (By similarity).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 115 | Essential for interaction with UBE2M | ||||
Sequence: C |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | ubiquitin ligase complex | |
Molecular Function | cullin family protein binding | |
Molecular Function | ubiquitin conjugating enzyme binding | |
Molecular Function | ubiquitin-like protein binding | |
Biological Process | positive regulation of protein neddylation | |
Biological Process | protein neddylation | |
Biological Process | regulation of protein neddylation | |
Biological Process | regulation of protein ubiquitination |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDCN1-like protein 1
- Short namesDCNL1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96GG9
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 15 | Loss of ubiquitin binding; when associated with A-16, A-44 and A-45. | ||||
Sequence: F → A | ||||||
Mutagenesis | 16 | Loss of ubiquitin binding; when associated with A-15, A-44 and A-45. | ||||
Sequence: M → A | ||||||
Mutagenesis | 44 | Loss of ubiquitin binding; when associated with A-15, A-16 and A-45. | ||||
Sequence: F → A | ||||||
Mutagenesis | 45 | Loss of ubiquitin binding; when associated with A-15, A-16 and A-44. | ||||
Sequence: F → A | ||||||
Mutagenesis | 115 | Loss of ability to stimulate cullin neddylation. | ||||
Sequence: C → A, G, I, L, T, or V | ||||||
Mutagenesis | 211 | Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5 CAND1 and RBX1; when associated with R-235 and A-241. Does not affect both nucleus and cytoplasm localization; when associated with R-235 and A-241. Reduces cullin neddylation; when associated with R-235 and A-241. Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4; when associated with R-235 and A-241. Loss of CUL2 interaction; when associated with R-235 and A-241. Reduces neddylation on CUL2; when associated with R-235 and A-241. Reduces interaction with VHL and HIF1A; when associated with R-235 and A-241. Does not affect interaction with SOCS1; when associated with R-235 and A-241. Does not affect DCUN1D1 monoubiquitylation; when associated with R-235 and A-241. | ||||
Sequence: D → A | ||||||
Mutagenesis | 235 | Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5 CAND1 and RBX1; when associated with A-211 and A-241.Does not affect both nucleus and cytoplasm localization; when associated with A-211 and A-241. Reduces cullin neddylation; when associated with A-211 and A-241. Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4; when associated with A-211 and A-241. Loss of CUL2 interaction; when associated with A-211 and A-241. Reduces neddylation on CUL2; when associated with A-211 and A-241. Reduces interaction with VHL and HIF1A; when associated with A-211 and A-241. Does not affect interaction with SOCS1; when associated with A-211 and A-241. Does not affect DCUN1D1 monoubiquitylation; when associated with A-211 and A-241. | ||||
Sequence: A → R | ||||||
Mutagenesis | 241 | Loss of interaction with CUL1, CUL2, CUL3, CULA4, CULA5 CAND1 and RBX1; when associated with A-211 and R-235.Does not affect both nucleus and cytoplasm localization; when associated withA-211 and R-235. Reduces cullin neddylation; when associated with A-211 and R-235. Loss of interaction with CUL1, CUL2, CUL3, CULA4 and CULA4; when associated with A-211 and R-235. Loss of CUL2 interaction; when associated with A-211 and R-235. Reduces neddylation on CUL2; when associated with A-211 and R-235. Reduces interaction with VHL and HIF1A; when associated with A-211 and R-235. Does not affect interaction with SOCS1; when associated with A-211 and R-235. Does not affect DCUN1D1 monoubiquitylation; when associated with A-211 and R-235. | ||||
Sequence: D → A | ||||||
Mutagenesis | 241 | Loss of binding to CAND1 and CUL-RBX1 complex but retains binding to UBE2M. | ||||
Sequence: D → N |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 180 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000129498 | 1-259 | UniProt | DCN1-like protein 1 | |||
Sequence: MNKLKSSQKDKVRQFMIFTQSSEKTAVSCLSQNDWKLDVATDNFFQNPELYIRESVKGSLDRKKLEQLYNRYKDPQDENKIGIDGIQQFCDDLALDPASISVLIIAWKFRAATQCEFSKQEFMDGMTELGCDSIEKLKAQIPKMEQELKEPGRFKDFYQFTFNFAKNPGQKGLDLEMAIAYWNLVLNGRFKFLDLWNKFLLEHHKRSIPKDTWNLLLDFSTMIADDMSNYDEEGAWPVLIDDFVEFARPQIAGTKSTTV | |||||||
Modified residue (large scale data) | 59 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Mono- and poly-ubiquitinated by ARIH2 and ARIH1. Monoubiquitination by ARIH2 is mediated by an interaction between autoubiquitinated ARIH2 and the UBA-like domain. The monoubiquitinated form preferentially interacts with non-neddylated cullins and modulates cullin RING ligase (CRL) complex composition and activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in pancreas, kidney, placenta, brain and heart. Weakly or not expressed in liver, skeletal muscle and lung. Strongly overexpressed in thyroid tumors, bronchioloalveolar carcinomas, and malignant tissues of squamous cell carcinoma of the oral tongue. Not overexpressed in aggressive adrenocortical carcinomas.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Part of an E3 complex for neddylation composed of cullins, RBX1, UBE2M and CAND1 (PubMed:18826954).
Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction (PubMed:18826954, PubMed:19617556, PubMed:23201271, PubMed:23401859, PubMed:26906416, PubMed:30587576).
Binds neddylated CUL1. Interacts (via the C-terminus 50 AA) directly with RBX1 (PubMed:18826954, PubMed:26906416).
Interacts (via DCUN1 domain) with the N-terminally acetylated form of UBE2M and UBE2F (PubMed:19617556, PubMed:23201271, PubMed:28581483).
Interacts preferentially with UBE2M-NEDD8 thioester (via N-terminus 1-26 AA) than with free UBE2M (PubMed:18826954, PubMed:25349211).
UBE2M N-terminal acetylation increases the affinity of this interaction by about 2 orders of magnitude (PubMed:21940857).
Interacts with CAND1; this interaction is indirect and is bridged by cullins such as CUL1 and CUL3 (PubMed:18826954, PubMed:26906416).
May also interact with regulators or subunits of cullin-RING ligases such as RNF7, ELOB and DDB1; these interactions are bridged by cullins (PubMed:26906416).
Component of VCB complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation (PubMed:23401859).
Interacts with VHL; this interaction triggers engagement of HIF1A in the VCB complex and is independent of CUL2 (PubMed:23401859).
Interacts with CUL2 independently of VHL (PubMed:23401859).
Interacts with SOCS1 and SOCS2 (PubMed:23401859).
Interacts with HIF1A; this interaction increases the interaction between VHL and DCUN1D1 (PubMed:23401859).
Interacts (via UBA-like domain) with ARIH2; promotes DCUN1D1 ubiquitination (PubMed:30587576).
Interacts (via the DCUN1 domain) with the unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5; these interactions promote the cullin neddylation and the identity of the cullin dictates the affinity of the interaction (PubMed:18826954, PubMed:19617556, PubMed:23201271, PubMed:23401859, PubMed:26906416, PubMed:30587576).
Binds neddylated CUL1. Interacts (via the C-terminus 50 AA) directly with RBX1 (PubMed:18826954, PubMed:26906416).
Interacts (via DCUN1 domain) with the N-terminally acetylated form of UBE2M and UBE2F (PubMed:19617556, PubMed:23201271, PubMed:28581483).
Interacts preferentially with UBE2M-NEDD8 thioester (via N-terminus 1-26 AA) than with free UBE2M (PubMed:18826954, PubMed:25349211).
UBE2M N-terminal acetylation increases the affinity of this interaction by about 2 orders of magnitude (PubMed:21940857).
Interacts with CAND1; this interaction is indirect and is bridged by cullins such as CUL1 and CUL3 (PubMed:18826954, PubMed:26906416).
May also interact with regulators or subunits of cullin-RING ligases such as RNF7, ELOB and DDB1; these interactions are bridged by cullins (PubMed:26906416).
Component of VCB complex that contains at least DCUN1D1, CUL2 and VHL; this complex triggers CUL2 neddylation and consequently cullin ring ligase (CRL) substrates polyubiquitylation (PubMed:23401859).
Interacts with VHL; this interaction triggers engagement of HIF1A in the VCB complex and is independent of CUL2 (PubMed:23401859).
Interacts with CUL2 independently of VHL (PubMed:23401859).
Interacts with SOCS1 and SOCS2 (PubMed:23401859).
Interacts with HIF1A; this interaction increases the interaction between VHL and DCUN1D1 (PubMed:23401859).
Interacts (via UBA-like domain) with ARIH2; promotes DCUN1D1 ubiquitination (PubMed:30587576).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q96GG9 | ABRAXAS2 Q15018 | 3 | EBI-740086, EBI-1056583 | |
BINARY | Q96GG9 | ARRDC3 Q96B67 | 10 | EBI-740086, EBI-2875665 | |
BINARY | Q96GG9 | CDIP1 Q9H305 | 3 | EBI-740086, EBI-2876678 | |
BINARY | Q96GG9 | DAZAP2 Q15038 | 9 | EBI-740086, EBI-724310 | |
BINARY | Q96GG9 | FAM168A Q92567-2 | 5 | EBI-740086, EBI-11978259 | |
BINARY | Q96GG9 | GMPPA Q96IJ6 | 3 | EBI-740086, EBI-750953 | |
BINARY | Q96GG9 | LZTS2 Q9BRK4 | 6 | EBI-740086, EBI-741037 | |
BINARY | Q96GG9 | PLEKHB2 Q96CS7 | 5 | EBI-740086, EBI-373552 | |
BINARY | Q96GG9 | SUSD6 Q92537 | 3 | EBI-740086, EBI-2866213 | |
BINARY | Q96GG9 | TMEM239 Q8WW34-2 | 3 | EBI-740086, EBI-11528917 | |
BINARY | Q96GG9 | TP53BP2 Q13625-3 | 3 | EBI-740086, EBI-10175039 | |
BINARY | Q96GG9 | TRIM39 Q9HCM9 | 4 | EBI-740086, EBI-739510 | |
BINARY | Q96GG9 | TRIM39 Q9HCM9-2 | 7 | EBI-740086, EBI-11523450 | |
BINARY | Q96GG9 | TRIM54 Q9BYV2 | 3 | EBI-740086, EBI-2130429 | |
BINARY | Q96GG9 | TRIM8 Q9BZR9 | 3 | EBI-740086, EBI-2340370 | |
BINARY | Q96GG9 | UBE2M P61081 | 5 | EBI-740086, EBI-1041660 | |
BINARY | Q96GG9 | VPS37B Q9H9H4 | 3 | EBI-740086, EBI-4400866 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 8-45 | UBA-like | ||||
Sequence: QKDKVRQFMIFTQSSEKTAVSCLSQNDWKLDVATDNFF | ||||||
Domain | 60-248 | DCUN1 | ||||
Sequence: LDRKKLEQLYNRYKDPQDENKIGIDGIQQFCDDLALDPASISVLIIAWKFRAATQCEFSKQEFMDGMTELGCDSIEKLKAQIPKMEQELKEPGRFKDFYQFTFNFAKNPGQKGLDLEMAIAYWNLVLNGRFKFLDLWNKFLLEHHKRSIPKDTWNLLLDFSTMIADDMSNYDEEGAWPVLIDDFVEFAR |
Domain
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins (PubMed:19617556, PubMed:23201271).
The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D1-cullin and DCUN1D1-E2 interaction affinities (PubMed:23201271, PubMed:28581483).
The UBA-like domain mediates interaction with autoubiquitylated ARIH2 leading to ubiquitin ligation to DCUN1D1 (PubMed:30587576).
The DCUN1 domain mediates the interaction with the N-terminally acetylated NEDD8-conjugating E2s enzyme leading to the NEDD8 transfer from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes; the neddylation efficiency correlates with the DCUN1D1-cullin and DCUN1D1-E2 interaction affinities (PubMed:23201271, PubMed:28581483).
The UBA-like domain mediates interaction with autoubiquitylated ARIH2 leading to ubiquitin ligation to DCUN1D1 (PubMed:30587576).
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length259
- Mass (Da)30,124
- Last updated2001-12-01 v1
- ChecksumF3709235E0610C54
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 134 | in Ref. 2; AAL78673 | ||||
Sequence: I → T | ||||||
Sequence conflict | 136 | in Ref. 1; AAG00606 | ||||
Sequence: K → Q | ||||||
Sequence conflict | 191-192 | in Ref. 2; AAL78673 | ||||
Sequence: KF → RL |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF292100 EMBL· GenBank· DDBJ | AAG00606.2 EMBL· GenBank· DDBJ | mRNA | ||
AF456425 EMBL· GenBank· DDBJ | AAL78672.1 EMBL· GenBank· DDBJ | mRNA | ||
AF456426 EMBL· GenBank· DDBJ | AAL78673.1 EMBL· GenBank· DDBJ | mRNA | ||
AK025764 EMBL· GenBank· DDBJ | BAB15235.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AK056335 EMBL· GenBank· DDBJ | BAG51680.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314480 EMBL· GenBank· DDBJ | BAG37084.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471052 EMBL· GenBank· DDBJ | EAW78342.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC009478 EMBL· GenBank· DDBJ | AAH09478.1 EMBL· GenBank· DDBJ | mRNA | ||
BC013163 EMBL· GenBank· DDBJ | AAH13163.2 EMBL· GenBank· DDBJ | mRNA |