Peptide name : Ubiquitin carboxyl-terminal hydrolase 22

Source/Organism : Human

Linear/Cyclic : Linear

Chirality : Not found

Peptide length: 525

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : Not specified

Assay time : Not found

Activity : Not found

Cell line : Not found

Cancer type : Not found

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 59959.9677 Dalton

Aliphatic index : 0.728

Instability index : 47.6534

Hydrophobicity (GRAVY) : -0.417

Isoelectric point : 8.369

Charge (pH 7) : 8.9198

Aromaticity : 0.097

Molar extinction coefficient (cysteine, cystine): (69330, 70955)

Hydrophobic/hydrophilic ratio : 0.89530685

hydrophobic moment : 0.1079

Missing amino acid : None

Most occurring amino acid : L

Most occurring amino acid frequency : 48

Least occurring amino acid : W

Least occurring amino acid frequency : 8

Secondary structure fraction (Helix, Turn, Sheet): (0.2, 0.2, 0.3)

SMILES Notation: 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1 : Zhang XY, et al. USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A. Cell Cycle. 2008; 7:1522-4. doi: 10.4161/cc.7.11.5962

2 : Lin Z, et al. USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 to suppress cell apoptosis and is required for mouse embryonic development. Mol Cell. 2012; 46:484-94. doi: 10.1016/j.molcel.2012.03.024

3 : Karlowitz R, et al. USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING. Cell Death Dis. 2022; 13:684. doi: 10.1038/s41419-022-05124-w

4 : Huang X, et al. USP22 Deubiquitinates CD274 to Suppress Anticancer Immunity. Cancer Immunol Res. 2019; 7:1580-1590. doi: 10.1158/2326-6066.CIR-18-0910

5 : Lee HJ, et al. The expression patterns of deubiquitinating enzymes, USP22 and Usp22. Gene Expr Patterns. 2006; 6:277-84. doi: 10.1016/j.modgep.2005.07.007

6 : Gerhard DS, et al. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004; 14:2121-7. doi: 10.1101/gr.2596504

7 : Bechtel S, et al. The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007; 8:399. doi: 10.1186/1471-2164-8-399

8 : Roedig J, et al. USP22 controls necroptosis by regulating receptor-interacting protein kinase 3 ubiquitination. EMBO Rep. 2021; 22:e50163. doi: 10.15252/embr.202050163

9 : Cai Z, et al. USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2. J Exp Med. 2020; 217:(unknown pages). doi: 10.1084/jem.20191174

10 : Choudhary C, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009; 325:834-40. doi: 10.1126/science.1175371

11 : Van Damme P, et al. N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012; 109:12449-54. doi: 10.1073/pnas.1210303109

12 : Li W, et al. Cytoplasmic ATXN7L3B Interferes with Nuclear Functions of the SAGA Deubiquitinase Module. Mol Cell Biol. 2016; 36:2855-2866. doi: 10.1128/MCB.00193-16

13 : Lin Z, et al. Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1. Cell Discov. 2015; 1:15028-. doi: 10.1038/celldisc.2015.28

14 : Zhao Y, et al. A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing. Mol Cell. 2008; 29:92-101. doi: 10.1016/j.molcel.2007.12.011

15 : Zhang XY, et al. The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol Cell. 2008; 29:102-11. doi: 10.1016/j.molcel.2007.12.015

16 : Kikuno R, et al. Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1999; 6:197-205. doi: 10.1093/dnares/6.3.197

Paper title : USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A.

Doi : https://doi.org/10.4161/cc.7.11.5962

Abstract : Initial studies of the mammalian hSAGA transcriptional coactivator complex identified the acetyltransferase hGCN5/PCAF as the only known enzymatic subunit. Recently we demonstrated that the ubiquitin hydrolase USP22 comprises a second enzymatic subunit of hSAGA, and that is required for activator-driven transcription. USP22 is expressed with polycomb ubiquitin ligases in an 11 gene signature that defines therapy-resistant tumors. At the biochemical level, these Polycomb proteins function as global transcriptional repressors by catalyzing the ubiquitylation of histone H2A. In yeast, the USP22 homolog functions as a transcriptional coactivator by removing ubiquitin from a distinct core histones, H2B. Given that USP22 is expressed in cancer as part of an 11 gene signature that includes transcriptional repressors which ubiquitylate H2A, it seemed possible that USP22 might activate transcription in part via the deubiquitylation of this same substrate. As reported here, biochemical analysis of the substrate specificity of USP22 reveals that it deubiquitylates histone H2A in addition to H2B. This finding supports a model in which the H2A ubiquitin hydrolase USP22 is coordinately expressed with Polycomb H2A ubiquitin ligases in order that the transcription of certain critical transforming genes be maintained in the face of the global repression mediated by Polycomb.

Paper title : USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 to suppress cell apoptosis and is required for mouse embryonic development.

Doi : https://doi.org/10.1016/j.molcel.2012.03.024

Abstract : The NAD-dependent histone deacetylase Sirt1 antagonizes p53 transcriptional activity to regulate cell-cycle progression and apoptosis. We have identified a ubiquitin-specific peptidase, USP22, one of the 11 death-from-cancer signature genes that are critical in controlling cell growth and death, as a positive regulator of Sirt1. USP22 interacts with and stabilizes Sirt1 by removing polyubiquitin chains conjugated onto Sirt1. The USP22-mediated stabilization of Sirt1 leads to decreasing levels of p53 acetylation and suppression of p53-mediated functions. In contrast, depletion of endogenous USP22 by RNA interference destabilizes Sirt1, inhibits Sirt1-mediated deacetylation of p53 and elevates p53-dependent apoptosis. Genetic deletion of the usp22 gene results in Sirt1 instability, elevated p53 transcriptional activity and early embryonic lethality in mice. Our study elucidates a molecular mechanism in suppression of cell apoptosis by stabilizing Sirt1 in response to DNA damage and reveals a critical physiological function of USP22 in mouse embryonic development.

Paper title : USP22 controls type III interferon signaling and SARS-CoV-2 infection through activation of STING.

Doi : https://doi.org/10.1038/s41419-022-05124-w

Abstract : Pattern recognition receptors (PRRs) and interferons (IFNs) serve as essential antiviral defense against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Type III IFNs (IFN-λ) exhibit cell-type specific and long-lasting functions in auto-inflammation, tumorigenesis, and antiviral defense. Here, we identify the deubiquitinating enzyme USP22 as central regulator of basal IFN-λ secretion and SARS-CoV-2 infections in human intestinal epithelial cells (hIECs). USP22-deficient hIECs strongly upregulate genes involved in IFN signaling and viral defense, including numerous IFN-stimulated genes (ISGs), with increased secretion of IFN-λ and enhanced STAT1 signaling, even in the absence of exogenous IFNs or viral infection. Interestingly, USP22 controls basal and 2'3'-cGAMP-induced STING activation and loss of STING reversed STAT activation and ISG and IFN-λ expression. Intriguingly, USP22-deficient hIECs are protected against SARS-CoV-2 infection, viral replication, and the formation of de novo infectious particles, in a STING-dependent manner. These findings reveal USP22 as central host regulator of STING and type III IFN signaling, with important implications for SARS-CoV-2 infection and antiviral defense.

Paper title : USP22 Deubiquitinates CD274 to Suppress Anticancer Immunity.

Doi : https://doi.org/10.1158/2326-6066.CIR-18-0910

Abstract : PD-1 (CD279)-PD-L1 (CD274) inhibitory signaling is critical for cancer immune evasion, and thus has become one of the major targets in anticancer immunotherapy. There are several studies that demonstrate the potent effects of posttranslational modifications of CD274 on immune inactivation and suppression, such as ubiquitination, phosphorylation, glycosylation, and palmitoylation. However, the regulatory mechanisms for CD274 deubiquitination are still largely unclear. Here, we identified ubiquitin-specific protease 22 (USP22) as a novel deubiquitinase of CD274. USP22 directly interacted with the C terminus of CD274, inducing its deubiquitination and stabilization. Across multiple cancer types, USP22 was highly expressed and frequently altered in liver cancer, closely correlating with poor prognosis of these patients. Genetic depletion of USP22 inhibited liver cancer growth in an immune system-dependent manner, increased tumor immunogenicity and tumor-infiltrating lymphocytes, and improved therapeutic efficacy of CD274-targeted immunotherapy and CDDP-based chemotherapy in mice. We demonstrate that targeting USP22 is a promising strategy to potentiate anticancer immunity for CD274-amplified cancer.

Paper title : The expression patterns of deubiquitinating enzymes, USP22 and Usp22.

Doi : https://doi.org/10.1016/j.modgep.2005.07.007

Abstract : Deubiquitinating enzymes regulate a number of cellular mechanisms including pre-implantation, growth and differentiation, oncogenesis, cell cycle progression, transcriptional activation, and signal transduction. In this study, we have identified a novel human deubiquitinating enzyme gene, USP22, and its mouse homologue, Usp22. They encode 525 amino acids (approximate MW: 60kDa) and contains Cys, Asp (I), His and Asp/Asn (II), the highly conserved domains of the UBP family of deubiquitinating enzymes. The biochemical assay revealed that they have deubiquitinating enzyme activity. Northern blot analysis for USP22 showed moderate expression in various organs including human heart and skeletal muscle, and weak expression in lung and liver. However, Usp22 is expressed strongly in brain and weakly in other organs. We investigated the expression level of Usp22 mRNA and the localization during implantation and early pregnancy by in situ hybridization. Interestingly, Northern blot analysis showed the strong expression of Usp22 between embryonic days E10.5 and E12.5. Whole mount in situ hybridization staining revealed that Usp22 was expressed in the midbrain, forebrain, hindbrain and dorsal root ganglia of embryos at E12.5. Embryos at E12.5 showed the pronounced expression of Usp22 during the early embryonic development, although its expression was not detectable in the gut, liver and heart.

Paper title : The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

Doi : https://doi.org/10.1101/gr.2596504

Abstract : The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

Paper title : The full-ORF clone resource of the German cDNA Consortium.

Doi : https://doi.org/10.1186/1471-2164-8-399

Abstract : BACKGROUND: With the completion of the human genome sequence the functional analysis and characterization of the encoded proteins has become the next urging challenge in the post-genome era. The lack of comprehensive ORFeome resources has thus far hampered systematic applications by protein gain-of-function analysis. Gene and ORF coverage with full-length ORF clones thus needs to be extended. In combination with a unique and versatile cloning system, these will provide the tools for genome-wide systematic functional analyses, to achieve a deeper insight into complex biological processes. RESULTS: Here we describe the generation of a full-ORF clone resource of human genes applying the Gateway cloning technology (Invitrogen). A pipeline for efficient cloning and sequencing was developed and a sample tracking database was implemented to streamline the clone production process targeting more than 2,200 different ORFs. In addition, a robust cloning strategy was established, permitting the simultaneous generation of two clone variants that contain a particular ORF with as well as without a stop codon by the implementation of only one additional working step into the cloning procedure. Up to 92 % of the targeted ORFs were successfully amplified by PCR and more than 93 % of the amplicons successfully cloned. CONCLUSION: The German cDNA Consortium ORFeome resource currently consists of more than 3,800 sequence-verified entry clones representing ORFs, cloned with and without stop codon, for about 1,700 different gene loci. 177 splice variants were cloned representing 121 of these genes. The entry clones have been used to generate over 5,000 different expression constructs, providing the basis for functional profiling applications. As a member of the recently formed international ORFeome collaboration we substantially contribute to generating and providing a whole genome human ORFeome collection in a unique cloning system that is made freely available in the community.

Paper title : USP22 controls necroptosis by regulating receptor-interacting protein kinase 3 ubiquitination.

Doi : https://doi.org/10.15252/embr.202050163

Abstract : Dynamic control of ubiquitination by deubiquitinating enzymes is essential for almost all biological processes. Ubiquitin-specific peptidase 22 (USP22) is part of the SAGA complex and catalyzes the removal of mono-ubiquitination from histones H2A and H2B, thereby regulating gene transcription. However, novel roles for USP22 have emerged recently, such as tumor development and cell death. Apart from apoptosis, the relevance of USP22 in other programmed cell death pathways still remains unclear. Here, we describe a novel role for USP22 in controlling necroptotic cell death in human tumor cell lines. Loss of USP22 expression significantly delays TNFα/Smac mimetic/zVAD.fmk (TBZ)-induced necroptosis, without affecting TNFα-mediated NF-κB activation or extrinsic apoptosis. Ubiquitin remnant profiling identified receptor-interacting protein kinase 3 (RIPK3) lysines 42, 351, and 518 as novel, USP22-regulated ubiquitination sites during necroptosis. Importantly, mutation of RIPK3 K518 reduced necroptosis-associated RIPK3 ubiquitination and amplified necrosome formation and necroptotic cell death. In conclusion, we identify a novel role of USP22 in necroptosis and further elucidate the relevance of RIPK3 ubiquitination as crucial regulator of necroptotic cell death.

Paper title : USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2.

Doi : https://doi.org/10.1084/jem.20191174

Abstract : USP22 is a cytoplasmic and nuclear deubiquitinating enzyme, and the functions of cytoplasmic USP22 are unclear. Here, we discovered that cytoplasmic USP22 promoted nuclear translocation of IRF3 by deubiquitianting and stabilizing KPNA2 after viral infection. Viral infection induced USP22-IRF3 association in the cytoplasm in a KPNA2-depedent manner, and knockdown or knockout of USP22 or KPNA2 impaired IRF3 nuclear translocation and expression of downstream genes after viral infection. Consistently, Cre-ER Usp22fl/fl or Lyz2-Cre Usp22fl/fl mice produced decreased levels of type I IFNs after viral infection and exhibited increased susceptibility to lethal viral infection compared with the respective control littermates. Mechanistically, USP22 deubiquitinated and stabilized KPNA2 after viral infection to facilitate efficient nuclear translocation of IRF3. Reconstitution of KPNA2 into USP22 knockout cells restored virus-triggered nuclear translocation of IRF3 and cellular antiviral responses. These findings define a previously unknown function of cytoplasmic USP22 and establish a mechanistic link between USP22 and IRF3 nuclear translocation that expands potential therapeutic strategies for infectious diseases.

Paper title : Lysine acetylation targets protein complexes and co-regulates major cellular functions.

Doi : https://doi.org/10.1126/science.1175371

Abstract : Lysine acetylation is a reversible posttranslational modification of proteins and plays a key role in regulating gene expression. Technological limitations have so far prevented a global analysis of lysine acetylation's cellular roles. We used high-resolution mass spectrometry to identify 3600 lysine acetylation sites on 1750 proteins and quantified acetylation changes in response to the deacetylase inhibitors suberoylanilide hydroxamic acid and MS-275. Lysine acetylation preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling, cell cycle, splicing, nuclear transport, and actin nucleation. Acetylation impaired phosphorylation-dependent interactions of 14-3-3 and regulated the yeast cyclin-dependent kinase Cdc28. Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other major posttranslational modifications.

Paper title : N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.

Doi : https://doi.org/10.1073/pnas.1210303109

Abstract : Protein N-terminal acetylation (Nt-acetylation) is an important mediator of protein function, stability, sorting, and localization. Although the responsible enzymes are thought to be fairly well characterized, the lack of identified in vivo substrates, the occurrence of Nt-acetylation substrates displaying yet uncharacterized N-terminal acetyltransferase (NAT) specificities, and emerging evidence of posttranslational Nt-acetylation, necessitate the use of genetic models and quantitative proteomics. NatB, which targets Met-Glu-, Met-Asp-, and Met-Asn-starting protein N termini, is presumed to Nt-acetylate 15% of all yeast and 18% of all human proteins. We here report on the evolutionary traits of NatB from yeast to human and demonstrate that ectopically expressed hNatB in a yNatB-Δ yeast strain partially complements the natB-Δ phenotypes and partially restores the yNatB Nt-acetylome. Overall, combining quantitative N-terminomics with yeast studies and knockdown of hNatB in human cell lines, led to the unambiguous identification of 180 human and 110 yeast NatB substrates. Interestingly, these substrates included Met-Gln- N-termini, which are thus now classified as in vivo NatB substrates. We also demonstrate the requirement of hNatB activity for maintaining the structure and function of actomyosin fibers and for proper cellular migration. In addition, expression of tropomyosin-1 restored the altered focal adhesions and cellular migration defects observed in hNatB-depleted HeLa cells, indicative for the conserved link between NatB, tropomyosin, and actin cable function from yeast to human.

Paper title : Cytoplasmic ATXN7L3B Interferes with Nuclear Functions of the SAGA Deubiquitinase Module.

Doi : https://doi.org/10.1128/MCB.00193-16

Abstract : The SAGA complex contains two enzymatic modules, which house histone acetyltransferase (HAT) and deubiquitinase (DUB) activities. USP22 is the catalytic subunit of the DUB module, but two adaptor proteins, ATXN7L3 and ENY2, are necessary for DUB activity toward histone H2Bub1 and other substrates. ATXN7L3B shares 74% identity with the N-terminal region of ATXN7L3, but the functions of ATXN7L3B are not known. Here we report that ATXN7L3B interacts with ENY2 but not other SAGA components. Even though ATXN7L3B localizes in the cytoplasm, ATXN7L3B overexpression increases H2Bub1 levels, while overexpression of ATXN7L3 decreases H2Bub1 levels. In vitro, ATXN7L3B competes with ATXN7L3 to bind ENY2, and in vivo, knockdown of ATXN7L3B leads to concomitant loss of ENY2. Unlike the ATXN7L3 DUB complex, a USP22-ATXN7L3B-ENY2 complex cannot deubiquitinate H2Bub1 efficiently in vitro Moreover, ATXN7L3B knockdown inhibits migration of breast cancer cells in vitro and limits expression of ER target genes. Collectively, our studies suggest that ATXN7L3B regulates H2Bub1 levels and SAGA DUB activity through competition for ENY2 binding.

Paper title : Ubiquitin-specific protease 22 is a deubiquitinase of CCNB1.

Doi : https://doi.org/10.1038/celldisc.2015.28

Abstract : The elevated level of CCNB1 indicates more aggressive cancer and poor prognosis. However, the factors that cause CCNB1 upregulation remain enigmatic. Herein, we identify USP22 as a CCNB1 interactor and discover that both USP22 and CCNB1 are dramatically elevated with a strong positive correlation in colon cancer tissues. USP22 stabilizes CCNB1 by antagonizing proteasome-mediated degradation in a cell cycle-specific manner. Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1. The ubiquitin ligase anaphase-promoting complex (APC/C) targets USP22 for degradation by using the substrate adapter CDC20 during cell exit from M phase, presumably allowing CCNB1 degradation. Finally, we discover that USP22 knockdown leads to slower cell growth and reduced tumor size. Our study demonstrates that USP22 is a CCNB1 deubiquitinase, suggesting that targeting USP22 might be an effective approach to treat cancers with elevated CCNB1 expression.

Paper title : A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing.

Doi : https://doi.org/10.1016/j.molcel.2007.12.011

Abstract : Transcriptional activators, several different coactivators, and general transcription factors are necessary to access specific loci in the dense chromatin structure to allow precise initiation of RNA polymerase II (Pol II) transcription. Histone acetyltransferase (HAT) complexes were implicated in loosening the chromatin around promoters and thus in gene activation. Here we demonstrate that the 2 MDa GCN5 HAT-containing metazoan TFTC/STAGA complexes contain a histone H2A and H2B deubiquitinase activity. We have identified three additional subunits of TFTC/STAGA (ATXN7L3, USP22, and ENY2) that form the deubiquitination module. Importantly, we found that this module is an enhancer of position effect variegation in Drosophila. Furthermore, we demonstrate that ATXN7L3, USP22, and ENY2 are required as cofactors for the full transcriptional activity by nuclear receptors. Thus, the deubiquitinase activity of the TFTC/STAGA HAT complex is necessary to counteract heterochromatin silencing and acts as a positive cofactor for activation by nuclear receptors in vivo.

Paper title : The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression.

Doi : https://doi.org/10.1016/j.molcel.2007.12.015

Abstract : Polycomb genes encode critical regulators of both normal stem cells and cancer stem cells. A gene signature that includes Polycomb genes and additional genes coregulated with Polycomb genes was recently identified. The expression of this signature has been reported to identify tumors with the cancer stem cell phenotypes of aggressive growth, metastasis, and therapy resistance. Most members of this 11 gene signature encode proteins with well-defined roles in human cancer. However, the function of the signature member USP22 remains unknown. We report that USP22 is a previously uncharacterized subunit of the human SAGA transcriptional cofactor complex. Within SAGA, USP22 deubiquitylates histone H2B. Furthermore, USP22 is recruited to specific genes by activators such as the Myc oncoprotein, where it is required for transcription. In support of a functional role within the Polycomb/cancer stem cell signature, USP22 is required for appropriate progression through the cell cycle.

Paper title : Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

Doi : https://doi.org/10.1093/dnares/6.3.197

Abstract : To extend our cDNA project for accumulating basic information on unidentified human genes, we newly determined the sequences of 100 cDNA clones from a set of size-fractionated human adult and fetal brain cDNA libraries, and predicted the coding sequences of the corresponding genes, named KIAA1019 to KIAA1118. The sequencing of these clones revealed that the average size of the inserts and corresponding open reading frames were 5.0 kb and 2.6 kb (880 amino acid residues), respectively. Database search of the predicted amino acid sequences classified 58 predicted gene products into the five functional categories, such as cell signaling/communication, cell structure/motility, nucleic acid management, protein management and cell division. It was also found that, for 34 gene products, homologues were detected in the databases, which were similar in sequence through almost the entire regions. The chromosomal locations of the genes were determined by using human-rodent hybrid panels unless their mapping data were already available in the public databases. The expression profiles of all the genes among 10 human tissues, 8 brain regions (amygdala, corpus callosum, cerebellum, caudate nucleus, hippocampus, substania nigra, subthalamic nucleus, and thalamus), spinal cord, fetal brain and fetal liver were also examined by reverse transcription-coupled polymerase chain reaction, products of which were quantified by enzyme-linked immunosorbent assay.