Containing transmembrane domains and a ubiquitin-like domain. Ubiquitin can be employed to modify proteins by either single or multiple ubiquitin conjugation to mark them for proteasomal destruction, endocytosis and binding to other proteins. Ubiquitin-like domain containing proteins are generally divided into two categories: the ubiquitin-like modifiers, such as SUMO, which can conjugate proteins similar to ubiquitin, and the integral UBL domain-containing proteins that are not conjugatable. The functions of UDPs are believed to be involved in a wide range of cellular processes. Some UDP proteins function by binding to the 26S proteasome via their UBL domain, whereas others function independent of the proteasome, including roles in receptor trafficking. The UBL containing proteins Plic-1/ubiquilin-1 and GABARAP/ubiquilin-2, both of which also contain a ubiquitin-associated domain, were shown to regulate GABAA receptor cellular localization and cell surface number. Tmub1/HOPS was reported to facilitate the recycling of AMPA receptors into synaptic membrane in cultured primary neurons. Tmub1/ HOPS was also found overexpressed during liver regeneration and is an essential constituent of centrosome assembly during cell cycles in culture. Like many UBL domain proteins, the physiological and molecular function of Tmub1 is far from being clear. To investigate the functions of Tmub1 in vivo, we performed Tmub1 gene deletion in mice, as part of a collaborative effort between Genentech and Lexicon Pharmaceuticals to analyze the function of about 500 secreted and transmembrane proteins. Excess reactive oxygen species and free radicals oxidize Hb to metHb and then further to hemichrome, a low-spin ferric hemoglobin derivative that binds to and clusters erythrocyte membrane protein band 3 by a process associated with erythrocyte senescence. HbC associates with erythrocyte membranes at a 5-fold greater rate than normal HbA and binds more tightly to the inner leaflet, where it is believed to cause more extensive clustering of band 3. Almost always, these problems are tackled with a Masitinib pipeline approach, where aCGH profiles of chromosomes for individual samples are first processed by a segmentation algorithm; individual segments are ”called” as gains or losses, based on their amplitude, using a choice of statistical procedure and significance threshold; and finally the called segments are used as input to a clustering algorithm or score-based method for determining significant common aberrations. The disadvantage of pipeline approaches, however, is that algorithmic choices and tuning parameters at each step may produce very different results, and mistakes or biases are propagated forward. For the first step, there are numerous segmentation algorithms that yield significantly different segment boundaries, leading to different calls of gains and losses.