Transcription regulatory networks in Caenorhabditis elegans

an ortholog of calcium-dependent serine endoproteinases, the kex2/subtilisin-like proprotein convertase that affects defecation cycle and anterior body contractions; and is expressed in all muscle cells except pharyngeal muscles.

ags-3 encodes an ortholog of mammalian AGS3, a receptor independent activator of G protein signalling, and of Drosophila RAPSYNOID; AGS-3 proteins have four GoLoco motifs; AGS-3 is involved in polarity and spindle orientation during early embryogenesis; a region of AGS-3 encompassing three GoLoco motifs specifically binds GOA-1 in yeast two-hybrid assays; AGS-3 is expressed in all muscles, intestine, and weakly in some head and ventral nerve cord neurons, with subcellular localization in strong dots.

aha-1 encodes an ortholog of human aryl-hydrocarbon receptor nuclear translocator; interacts with AHR-1 and HIF-1 in vitro, requires HIF-1 for proper localization, and is expressed ubiquitously.

alg-2 encodes a PAZ and PIWI-domain containing protein that is a member of the highly conserved eukaryotic RDE-1/AGO1/PIWI family of proteins that regulate posttranscriptional gene silencing (PTGS); ALG-2 functions with ALG-1 to control specific developmental timing events by positively regulating expression of small temporal RNAs (stRNAs) encoded by lin-4 and let-7; ALG-2 and ALG-1 are also required for RNAi in the germ line, although they are not required for RNAi in the soma; ALG-2 is expressed in nearly all cells from embryogenesis through adulthood and localizes to the cytoplasm.

alh-8 is orthologous to the human gene METHYLMALONATE-SEMIALDEHYDE DEHYDROGENASE (ALDH6A1; OMIM:603178), which when mutated leads to MMSDH deficiency.

aly-2 encodes an RRM motif-containing protein required for normal export of TRA-1/tra-2 mRNA complexes, and thus for normal hermaphroditism; ALY-2 is orthologous to human THOC4 (OMIM:604171), and paralogous to ALY-1 and ALY-3; in the absence of TRA-1, and in conjunction with NXF-1, ALY-2 and its paralog ALY-1 are required to bind the TRE 3' UTR element of tra-2 mRNA, and block tra-2 mRNA's export from the nucleus; aly-2(RNAi) animals have abnormal female (as opposed to hermaphrodite) sexual phenotypes; by orthology, ALY-2 is thought to promote recruitment of mRNA export factor to mRNAs; other than these sex-determination phenotypes, ALY-2 has no grossly obvious function in four-way RNAi assays of ALY-1/-3 and W04D2.6.

apc-2 encodes an ortholog of subunit 2 of anaphase-promoting complex (APC, a cyclin-specific E3 RING ubiquitin ligase); APC-2 and S. cerevisiae's Apc2p have 32% identity in their cullin domains (considered crucial for function), but otherwise share no obvious similarity; inactivating apc-2 with RNAi causes embryos to arrest at the meiotic one-cell stage, implying that APC-2 is required for the metaphase-to-anaphase transition of meiosis I; this RNAi phenotype of apc-2 is shared by apc-1, apc-4, apc-11, cdc-16, cdc-23, and cdc-27; by analogy with other APC subunits with hypomorphic alleles, APC-2 is likely to be required for asymmetrical segregation of cell fate determinants in two-cell embryos.

apl-1 encodes two almost identical isoforms orthologous to human APP (OMIM:104760, mutated in familial Alzheimer disease or cerebroarterial amyloidosis), APLP1 (OMIM:104775), and APLP2 (OMIM:104776); although native APL-1 is predicted to be membrane-bound until proteolytically cleaved, neuronal expression of a partial N-terminal extracellular region of APL-1 alone, containing either the E1 or the E2 domain, is sufficient for APL-1's normal functions in vivo (molting and morphogenesis, pharyngeal pumping, and progession past the L1 larval stage), indicating that APL-1 functions non-cell-autonomously; apl-1 is widely expressed in neurons, muscle, hypodermis, and supporting cells of larvae and adults; APL-1 contains a Cu(II)-binding domain; overexpressed APL-1 causes abnormal locomotion, infertility, and partial lethality, but the lethality of excess APL-1 can be partially suppressed by hypomorphic sel-12 mutations; apl-1 mutants show vacuoles in hypodermal cells, while having superfically normal neurons; apl-1 genetically interacts with feh-1 to affect pharyngeal pumping, and APL-1 binds the PTB2 domain of FEH-1 in vitro; apl-1 mutations are not suppressed by ced-3 or crt-1 mutations, and thus are unlikely to activate apoptosis or necrosis.

aps-1 encodes an adaptin: specifically, it encodes an ortholog of the sigma1 subunit of adaptor protein complex 1 (AP-1).