title: The human HERC family of ubiquitin ligases: novel members, genomic organization, expression profiling, and evolutionary aspects.
abstract: The HERC family of ubiquitin ligases is characterized by the presence of a HECT domain and one or more RCC1-like domains. We report the identification of two novel members, HERC4 and HERC6, and subdivide the family into one group of two large and one group of four small members according to protein size and domain structure. The small members share a similar genomic organization, three of them mapping to chromosomal region 4q22, indicating strong evolutionary cohesions. Phylogenetic analysis reveals that the HERC ancestor emerged in nematodes and that the family expanded throughout evolution. The mRNA expression pattern of the small human members was found to be diverse in selected tissues and cells; overexpressed proteins display a similar cytosolic distribution. These data indicate that the HERC family members exhibit similarities in many aspects, but also sufficient differences indicating functional diversity.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Medical University of Vienna, and Biomolecular Therapeutics, Brunnerstrasse 59, 1235 Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Hochrainer
authors.forename: Herbert
authors.initials: H
authors.lastname: Mayer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Baranyi
authors.forename: Berndr
authors.initials: B
authors.lastname: Binder
authors.forename: Joachim
authors.initials: J
authors.lastname: Lipp
authors.forename: Renate
authors.initials: R
authors.lastname: Kroismayr
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C480733:SOSTDC1 protein, human; C502268:HERC4 protein, human; C502269:HERC6 protein, human; D044767:Ubiquitin-Protein Ligases