Human Histone Chaperone ASF1A (ASF1A) belongs to the H3/H4 family of histone chaperone proteins. ASF1A is ubiquitously expressed in many cells and tissues, interacting with histones H3 and H4. ASF1A cooperates with Chromatin Assembly Factor 1 to promote replication-dependent chromatin assembly and with HIRA to promote replication-independent chromatin assembly. In addition, ASF1A is necessary for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit.
Asialoglycoprotein Receptor 1 (ASGPR1) is an endocytic recycling receptor; belongs to the long-form subfamily of the C-type/Ca2+-dependent lectin family. ASGPR consists of two noncovalently-linked subnits; ASGPR1 and ASGPR2. ASGPR1 mediates the endocytosis of plasma glycoproteins; recognizes terminal galactose and N-acetylgalactosamine units. When the ligand binds to to ASGPR1; results in the complex is internalized and transported to a sorting organelle; then ASGPR1 and ligand can be disassociated; ASGPR1 returns to the cell membrane surface.
Argininosuccinate Synthase (ASS1) is an urea cycle enzyme with a tetrameric structure composed of identical subunits. ASS1 is involved in the synthesis of arginine and catalyzes that condensation of citrulline and aspartate to argininosuccinate using ATP. ASS1 is important to the urea cycle as it catalyzes the important second last step in the arginine biosynthetic pathway. ASS1 mainly expressed in periportal hepatocytes, but also in most other body tissues. A deficiency of ASS1 causes citrullinemia (CTLN1), an autosomal recessive disease which is characterized by severe vomiting spells and mental retardation.
Astrocyticphosphoprotein PEA-15 (PEA15) is a death effector domain (DED)-containing protein. PEA15 is mainly expressed in the central nervous system, principally in astrocytes. Increased PEA15 levels affect tumorigenesis and cancer progression. PEA15 is overexpressed in breast cancers and gliomas as well as in type 2 diabetes. PEA15 blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. PEA15 also inhibits RPS6KA3 activities by holding it in the cytoplasm. In addition, PEA15 inhibits both TNFRSF6 and TNFRSF1A mediated CASP8 activity and apoptosis. At present, PEA15 expression is also a significant prognostic marker in ovarian cancer.
Putative Polycomb group protein ASXL1 involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). It acts as coactivator of RARA and RXRA through association with NCOA1. ASXL1 also acts as corepressor through recruitment of KDM1A and CBX5 to target genes in a cell-type specific manner; the function seems to involve differential recruitment of methylated histone H3 to respective promoters.
Ataxin-3 is a ubiquitously expressed nuclear protein that serves as a deubiquitinating enzyme (DUB) involved in protein homeostasis and quality control, myogenesis and degradation of misfolded chaperone substrates. As a DUB, it has two distinct features. Its N-terminal Josephin domain confers cysteine protease activity to Ataxin-3 which is important for hydrolyzing ubiquitin (Ub) linkages. The second important feature is its three Ub-interacting motifs (UIMs) through which it binds Ub conjugates and ubiquitinated proteins and bring them into proximity to trim or edit specific linkages within these Ub conjugates. It binds long poly-Ub chains and trims them. However, it has weak or no activity against chains of 4 or less Ub.
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