Golgi retention of human protein NEFA is mediated by its N‐terminal Leu/Ile‐rich region

Nesselhut, Jan; Jurgan, Ulrich; Onken, Elke; Götz, H.; Barnikol, Heinz Ulrich; Hirschfeld, Gregor; Barnikol-Watanabe, Shitsu; Hilschmann, Norbert

doi:10.1016/s0014-5793(01)03187-8

Cited by 22 publications

(12 citation statements)

References 30 publications

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“…While the retention of Golgi-resident proteins with TM domains is well-studied [125], retention of fully-luminal Golgi proteins is sparse. However, an amino-terminal leucine-rich region is essential for Golgi retention of the NEFA/NUC family of Ca 2+ -binding EF-hand/leucine zipper proteins [126]. None of the remaining DIA1-family motifs have a predicted function in proteins localized to the lumen of the ER or Golgi apparatus.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Deleted in Autism 1 Protein Family: Implications for Studying Cognitive Disorders

2011

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Autism spectrum disorders (ASDs) are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1) and cXorf36 or Deleted in Autism-1 Related (DIA1R) are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L), lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental retardation.

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Section: Discussionmentioning

confidence: 99%

Characterization of the Deleted in Autism 1 Protein Family: Implications for Studying Cognitive Disorders

2011

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“…This was proved by mutational studies wherein mutation of this specific proline residue abolished localization of calnuc to the Golgi apparatus (19). Similar to calnuc, NEFA or Nucb2 is also localized to the Golgi as evidenced by N-terminal deletion mutants (20). This stresses the fact that the signal for sorting to Golgi apparatus lies in the N-terminal region.…”

Section: Localization Distribution and Expressionmentioning

confidence: 63%

Calnuc: Emerging roles in calcium signaling and human diseases

et al. 2010

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SummaryCalnuc is a recently discovered multidomain protein with EF-hand calcium binding sites. Several studies have reported various interacting partners for calnuc and, therefore, also different sites of localization in the cell. It interacts with important molecules such as DNA, G protein, COX, and amyloid precursor protein among others in addition to being involved in stress response and trafficking. The immense possibilities (of various functions this protein might be involved in) implicate great future in medicine and physiology. Preliminary studies also implicate the possibility of calnuc being involved in some of the human diseases. These initial observations imply the functions that this protein might be involved in. This review emphasizes the importance of further research on this protein. IUBMBIUBMB Life, 62(6): [436][437][438][439][440][441][442][443][444][445][446] 2010

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“…NEFA was initially thought to bind DNA; however, it has been shown to be a Golgi localized calcium-binding protein [53,54]. The existence of NIP30 has been confirmed at the protein level and was initially identified by cDNA screens.…”

Section: Discussionmentioning

confidence: 99%

Comparative host protein interactions with HTLV-1 p30 and HTLV-2 p28: insights into difference in pathobiology of human retroviruses

et al. 2012

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BackgroundHuman T lymphotropic virus type-1 (HTLV-1) and type 2 (HTLV-2) are closely related human retroviruses, but have unique disease associations. HTLV-1 is the causative agent of an aggressive T-cell leukemia known as adult T-cell leukemia (ATL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other inflammatory diseases. HTLV-2 infection has not been clearly associated with any disease condition. Although both viruses can transform T cells in vitro, the HTLV-1 provirus is mainly detected in CD4+ T cells whereas HTLV-2 is mainly detected in CD8+ T cells of infected individuals. HTLV-1 and HTLV-2 encode accessory proteins p30 and p28, respectively, which share partial amino acid homology and are required for viral persistence in vivo. The goal of this study was to identify host proteins interacting with p30 and p28 in order to understand their role in pathogenesis.ResultsAffinity-tag purification coupled with mass spectrometric (MS) analyses revealed 42 and 22 potential interacting cellular partners of p30 and p28, respectively. Of these, only three cellular proteins, protein arginine methyltransferase 5 (PRMT5), hnRNP K and 60 S ribosomal protein L8 were detected in both p30 and p28 fractions. To validate the proteomic results, four interacting proteins were selected for further analyses using immunoblot assays. In full agreement with the MS analysis two cellular proteins REGγ and NEAF-interacting protein 30 (NIP30) selectively interacted with p30 and not with p28; heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) bound to p28 and not to p30; and PRMT5 interacted with both p30 and p28. Further studies demonstrated that reduced levels of PRMT5 resulted in decreased HTLV-2 viral gene expression whereas the viral gene expression of HTLV-1 was unchanged.ConclusionThe comparisons of p30 and p28 host protein interaction proteome showed striking differences with some degree of overlap. PRMT5, one of the host proteins that interacted with both p30 and p28 differentially affected HTLV-1 and HTLV-2 viral gene expression suggesting that PRMT5 is involved at different stages of HTLV-1 and HTLV-2 biology. These findings suggest that distinct host protein interaction profiles of p30 and p28 could, in part, be responsible for differences in HTLV-1 and HTLV-2 pathobiology. This study provides new avenues of investigation into mechanisms of viral infection, tropism and persistence.

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Golgi retention of human protein NEFA is mediated by its N‐terminal Leu/Ile‐rich region

Cited by 22 publications

References 30 publications

Characterization of the Deleted in Autism 1 Protein Family: Implications for Studying Cognitive Disorders

Characterization of the Deleted in Autism 1 Protein Family: Implications for Studying Cognitive Disorders

Calnuc: Emerging roles in calcium signaling and human diseases

Comparative host protein interactions with HTLV-1 p30 and HTLV-2 p28: insights into difference in pathobiology of human retroviruses

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