This entry represents Arb2 domain that was first described in Argonaute-binding protein 2 from S. pombe, from which it gets the name. Arb2 protein is the orthologue of FAM172 from animals, including FAM12A from human, a protein associated with CHARGE syndrome, a severe multi-organ developmental disorder mainly affecting derivatives of cranial and cardiac neural crest cells (NCCs). A general pathological mechanism for CHARGE syndrome has been suggested to be a spliceosomopathy, the perturbation of chromatin-mediated alternative splicing [, ]. FAM172A and its homologues contain a large ARB2 domain split into two halves by a classical bipartite NLS that helps to stabilize the chromatin-spliceosome interface as part of a complex that includes CHD7 and AGO2 []. It has been suggested that FAM172A can connect the alternative splicing machinery to specific transcribed chromatin regions [, ]. Arb2 from S.pombe is a member of the argonaute siRNA chaperone (ARC) complex which is required for histone H3K9 methylation, heterochromatin assembly and siRNA generation []. This domain has clear homology to ��/��-hydrolases but it lacks the catalytic triad of these enzymes.
Members of this entry contain the Arb2 domain that gets its name from S. pombe Argonaute-binding protein 2 (Arb2), which is the orthologue of the vertebrate cotranscriptional regulator ARB2A (also known as FAM172 family) []. Human FAM172A protein is associated with CHARGE syndrome, a severe multi-organ developmental disorder mainly affecting derivatives of cranial and cardiac neural crest cells (NCCs). CHARGE syndrome has been suggested to be a spliceosomopathy, due to perturbation of chromatin-mediated alternative splicing [, ]. FAM172A and its homologues contain a large Arb2 domain split into two halves by a classical bipartite NLS that helps to stabilise the chromatin-spliceosome interface as part of a complex that includes CHD7 and AGO2 []. It has been suggested that FAM172A can connect the alternative splicing machinery to specific transcribed regions [, ]. S. pombe Arb2 is a member of the argonaute siRNA chaperone (ARC) complex which is required for histone H3K9 methylation, heterochromatin assembly and siRNA generation. The Arb2 domain has clear homology to ��/��-hydrolases but it lacks the catalytic triad of these enzymes.
