title: Hu-K4 is a ubiquitously expressed type 2 transmembrane protein associated with the endoplasmic reticulum.
abstract: Hu-K4 is a human protein homologous to the K4L protein of vaccinia virus. Due to the presence of two HKD motifs, Hu-K4 was assigned to the family of Phospholipase D proteins although so far no catalytic activity has been shown. The Hu-K4 mRNA is found in many human organs with highest expression levels in the central nervous system. We extended the ORF of Hu-K4 to the 5' direction. As a consequence the protein is 53 amino acids larger than originally predicted, now harbouring a putative transmembrane domain. The exon/intron structure of the Hu-K4 gene reveals extensive alternative splicing in the 5' untranslated region. Due to the absence of G/C-rich regions and upstream ATG codons, the mRNA isoform in brain may be translated with higher efficacy leading to a high Hu-K4 protein concentration in this tissue. Using a specific antiserum produced against Hu-K4 we found that Hu-K4 is a membrane-bound protein colocalizing with protein disulfide isomerase, a marker of the endoplasmic reticulum. Glycosylation of Hu-K4 as shown by treatment with peptide N-glycosidase F or tunicamycin indicates that Hu-K4 has a type 2 transmembrane topology.
authors.affiliation: Center of Experimental Medicine, Institute of Biochemistry and Molecular Biology II: University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Antonia
authors.initials: A
authors.lastname: Munck
authors.forename: Christopher
authors.initials: C
authors.lastname: Böhm
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Seibel
authors.forename: Zara
authors.initials: Z
authors.lastname: Hashemol Hosseini
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hampe
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger