RUBCN

The protein encoded by this gene is a negative regulator of autophagy and endocytic trafficking and controls endosome maturation. This protein contains two conserved domains, an N-terminal RUN domain and a C-terminal DUF4206 domain. The RUN domain is involved in Ras-like GTPase signaling, and the DUF4206 domain contains a diacylglycerol (DAG) binding-like motif. Mutation in this gene results in deletion of the DAG binding-like motif and causes a recessive ataxia. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

Full Name

RUN And Cysteine Rich Domain Containing Beclin 1 Interacting Protein

Function

Inhibits PIK3C3 activity; under basal conditions negatively regulates PI3K complex II (PI3KC3-C2) function in autophagy. Negatively regulates endosome maturation and degradative endocytic trafficking and impairs autophagosome maturation process. Can sequester UVRAG from association with a class C Vps complex (possibly the HOPS complex) and negatively regulates Rab7 activation (PubMed:20974968, PubMed:21062745).
Involved in regulation of pathogen-specific host defense of activated macrophages. Following bacterial infection promotes NADH oxidase activity by association with CYBA thereby affecting TLR2 signaling and probably other TLR-NOX pathways. Stabilizes the CYBA:CYBB NADPH oxidase heterodimer, increases its association with TLR2 and its phagosome trafficking to induce antimicrobial burst of ROS and production of inflammatory cytokines (PubMed:22423966).
Following fungal or viral infection (implicating CLEC7A (dectin-1)-mediated myeloid cell activation or DDX58/RIG-I-dependent sensing of RNA viruses) negatively regulates pro-inflammatory cytokine production by association with CARD9 and sequestering it from signaling complexes (PubMed:22423967).

Biological Process

Biological Process autophagyIEA:UniProtKB-KW
Biological Process endocytosisIEA:UniProtKB-KW
Biological Process immune system processIEA:UniProtKB-KW
Biological Process multivesicular body sorting pathwayManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Biological Process negative regulation of autophagosome maturationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of autophagyManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of endocytosisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of phosphatidylinositol 3-kinase activityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process phagocytosisIEA:UniProtKB-KW

Cellular Location

Late endosome
Lysosome
Early endosome
Predominantly located in late endosomes/lysosomes, only partially detected in early endosome and not at all in the Golgi apparatus.

Involvement in disease

Spinocerebellar ataxia, autosomal recessive, 15 (SCAR15):
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR15 patients manifest cerebellar ataxia in early childhood and delayed motor development with delayed walking. Additional features include dysarthria, upper limb involvement, abnormal eye movements, and hyporeflexia.