E3 ubiquitin-protein ligase LNX; ligand of Numb-protein X 1; Numb-binding protein 1 (LNX1, LNX, UNQ574/PRO1136)

Function

• E3 ubiquitin-protein ligase
• mediates ubiquitination & subsequent proteasomal degradation of NUMB
• E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester & then directly transfers the ubiquitin to targeted substrates
• mediates ubiquitination of isoform p66 & isoform p72 of NUMB, does not ubiquitinate isoform p71 or isoform p65 of NUMB (putative)
• isoform 2 provides an endocytic scaffold for IGSF5/JAM4
• protein modification; protein ubiquitination
• interacts with the phosphotyrosine interaction domain of all isoforms of NUMB (putative)
• interacts with endogenous retrovirus K protein Np9
• IGSF5/JAM4 interacts with isoform 2 through the second PDZ domain, other isoforms may also interact with IGSF5/JAM4 (putative)

Structure

• the NPXY motif is necessary for the interaction with the PID domain of NUMB; but, it is not sufficient
• the PDZ 1 domain participates in the interaction with the PID domain of NUMB, & participates in the isoform-specific ubiquitination of NUMB
• the PDZ 2 domain of isoform 2 participates in the interaction with IGSF5/JAM4; other isoforms containing this domain may also interact with IGSF5/JAM4 (putative)
• contains 4 PDZ domain (DHR domain)s
• contains 1 RING-type Zn+2 finger

Compartment

cytoplasm (putative)

Alternative splicing

named isoforms=2

Expression

• expressed in heart, placenta, kidney, pancreas & brain

Pathology

• interacts with the Coxsackievirus & adenovirus receptor CXADR

More general terms

• WD repeat protein family
• E3 ubiquitin ligase
• ring finger protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=84708
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:84708
• OMIM: https://mirror.omim.org/entry/609732
• UniProt: http://www.uniprot.org/uniprot/Q8TBB1.html