RING finger protein 19A; E3 ubiquitin-protein ligase RNF19A; double ring-finger protein; dorfin; p38 (RNF19A, RNF19)

Function

• E3 ubiquitin-protein ligase
• accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 & UBE2L6 in the form of a thioester & directly transfers the ubiquitin to targeted substrates, such as SNCAIP or CASR
• specifically ubiquitinates pathogenic SOD1 variants, which leads to their proteasomal degradation & to neuronal protection
• protein modification; protein ubiquitination
• phosphorylated upon DNA damage, probably by ATM or ATR
• interacts with UBE2L3 & UBE2L6
• interacts with transcription factor Sp1
• interacts with VCP, CASR, SNCAIP & with some SOD1 variants which cause amyotrophic lateral sclerosis, but not with wild-type SOD1

Structure

• belongs to the RBR family, RNF19 subfamily
• contains 1 IBR-type Zn+2 finger
• contains 2 RING-type Zn+2 fingers

Compartment

• membrane (putative)
• cytoplasm, cytoskeleton, centrosome

Alternative splicing

named isoforms=3

Expression

• widely expressed
• highest levels in heart
• ubiquitously expressed in the central nervous system

Pathology

• present in hyaline inclusion bodies specifically found in motor neurons from amyotrophic lateral sclerosis patients
• present in Lewy bodies specifically found in neurons from Parkinson's disease patients

More general terms

• ring finger protein
• E3 ubiquitin ligase
• phosphoprotein
• transmembrane 2 protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=25897
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:25897
• OMIM: https://mirror.omim.org/entry/607119
• UniProt: http://www.uniprot.org/uniprot/Q9NV58.html