DCN1-like protein 1

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).

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).

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.

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.

• Nucleus
• Cytoplasm
• The ubiquitinated form is localized in the cytoplasm.

DCN1, DCUN1L1, RP42, SCCRO, DCUN1D1, DCN1-like protein 1, DCNL1, DCUN1 domain-containing protein 1, Defective in cullin neddylation protein 1-like protein 1, Squamous cell carcinoma-related oncogene

• entrezGene:54165
• omim:605905
• swissprot:Q96GG9

Proteins

Oncology

30124Da