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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ERD2 gene of Saccharomyces cerevisiae encodes the HDEL receptor that sorts ER proteins; it is essential for growth. In the absence of Erd2p the Golgi apparatus is both functionally and morphologically perturbed. Here we describe the isolation of four SED genes (suppressors of the erd2-deletion) which, when present in multiple copies, allow cells to grow in the absence of ERD2. The suppressed strains secrete the ER protein BiP and their internal membranes show a variety of morphological abnormalities. Sequence analysis indicates that all these SED genes encode membrane proteins: SED1 encodes a probable cell surface glycoprotein; SED2 is identical to SEC12, a gene required for the formation of ER-derived transport vesicles; SED4 encodes a protein whose cytoplasmic domain is 45% identical to that of Sec12p; SED3 is DPM1, the structural gene for dolichol-P-mannose synthase. We suggest that the absence of ERD2 causes an imbalance between membrane flow into and out of the Golgi apparatus, and that the SED gene products can compensate for this either by slowing transport from the ER or by stimulating vesicle budding from Golgi membranes.
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PMID:Genes that allow yeast cells to grow in the absence of the HDEL receptor. 132 59

We have cloned the gene for the resident luminal ER protein BiP from the fission yeast, Schizosaccharomyces pombe. The predicted protein product is equally divergent from the budding yeast and mammalian homologues. Disruption of the BiP gene in S. pombe is lethal and BiP mRNA levels are regulated by a variety of stresses including heat shock. Immunofluorescence of cells expressing an epitope-tagged BiP protein show it to be localized to the nuclear envelope, around the cell periphery and in a reticular structure through the cytoplasm. Unexpectedly, we find the BiP protein contains an N-linked glycosylation site which can be utilized. The C-terminal four amino acids of BiP are Ala-Asp-Glu-Leu, a new variant of the XDEL sequence found at the C-termini of luminal endoplasmic reticulum proteins. To determine whether this sequence acts as a sorting signal in S.pombe we expressed an acid phosphatase fusion protein extended at its C-terminus with the amino acids ADEL. Analysis of the sorting of this fusion protein indicates that the ADEL sequence is sufficient to cause the retention of proteins in the endoplasmic reticulum. The sequences DDEL, HDEL and KDEL can also direct ER-retention of acid phosphatase in S.pombe.
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PMID:Analysis of the BiP gene and identification of an ER retention signal in Schizosaccharomyces pombe. 137 79

We have previously shown that the C-terminal sequence HDEL acts as a retention signal for luminal endoplasmic reticulum (ER) proteins in Saccharomyces cerevisiae, and that it is possible to isolate mutants that fail to retain an invertase fusion protein bearing this signal. Analysis of many such mutants defines two genes, ERD1 and ERD2. Cells lacking the ERD1 gene secrete the endogenous ER protein, BiP. Under normal growth conditions, the rate of secretion is equivalent to the rate at which wild-type cells secrete a modified form of BiP that lacks the HDEL signal altogether. Thus, erd1 cells show a profound disruption of the retention system. The mutant cells have no gross abnormality of their intracellular membrane system, but show defects in the Golgi-dependent modification of glycoproteins. We suggest that sorting of luminal ER proteins normally occurs in the Golgi, and that the function of ERD1 is required for the correct interaction of an HDEL receptor with its ligands. The sequence of ERD1 predicts a membrane protein with several transmembrane domains, a conclusion supported by analysis of ERD1-SUC2 fusion proteins.
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PMID:ERD1, a yeast gene required for the retention of luminal endoplasmic reticulum proteins, affects glycoprotein processing in the Golgi apparatus. 217 21

Luminal ER proteins carry a signal at their C terminus that prevents their secretion; in S. cerevisiae this signal is the tetrapeptide HDEL. Indirect evidence suggests that HDEL is recognized by a receptor that retrieves ER proteins from the secretory pathway and returns them to the ER, and a candidate for this receptor is the product of the ERD2 gene (see accompanying paper). We show here that presumptive ER proteins from the budding yeast K. lactis can terminate either with HDEL or, in the case of BiP, with DDEL. S. cerevisiae does not efficiently recognize DDEL as a retention signal, but exchange of its ERD2 gene for the corresponding gene from K. lactis allows equal recognition of DDEL and HDEL. Thus the specificity of the retention system is determined by the ERD2 gene. We conclude that ERD2 encodes the receptor that sorts luminal ER proteins.
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PMID:The ERD2 gene determines the specificity of the luminal ER protein retention system. 219 71

The yeast KAR2 gene was isolated by complementation of a mutation that blocks nuclear fusion. The predicted KAR2 protein sequence is most homologous to mammalian BiP/GRP78 and has several structural features in common with it: a functional secretory signal sequence, a yeast endoplasmic reticulum retention signal (HDEL) at the carboxyl terminus, and the absence of potential N-linked glycosylation sites. Moreover KAR2 is regulated like BiP/GRP78: the level of mRNA is increased by drug treatments and mutations that cause accumulation of secretory precursors in the endoplasmic reticulum. However, unlike BiP/GRP78, KAR2 is also regulated by heat shock. Deletion of the KAR2 gene generated a recessive lethal mutation, showing that BiP/GRP78 function is required for cell viability.
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PMID:KAR2, a karyogamy gene, is the yeast homolog of the mammalian BiP/GRP78 gene. 266 Oct 18

The ERD2 gene of Saccharomyces cerevisiae encodes the receptor which retrieves HDEL-containing containing ER proteins from the Golgi apparatus. Viable erd2 mutants have been isolated that show no obvious HDEL-dependent retention of the luminal ER protein BiP, suggesting that retrieval of HDEL proteins is not essential for growth. However, cells that lack Erd2p completely have a defective Golgi apparatus and cannot grow. This observation led to the suggestion that the receptor had a second function, possibly related to its ability to recycle from Golgi to ER. In this paper we investigate the requirements for Erd2p to support growth. We show that mutations that block its recycling also prevent growth. In addition, we show that all mutant receptors that can support growth have a residual ability to retrieve BiP, which is detectable when they are overexpressed. Mere recycling of an inactive form of the receptor, mediated by a cytoplasmic KKXX sequence, is not sufficient for growth. Furthermore, saturation of the receptor by expression of an HDEL-tagged version of pro-alpha factor inhibits growth, even of strains that do not show obvious BiP retention. We conclude that growth requires the HDEL-dependent retrieval of one or more proteins, and that these proteins can be recognized even under conditions where BiP is secreted. Genetic screens have failed to identify any one protein whose loss could account for the Erd2p requirement. Therefore, a growth may require the retention of multiple HDEL proteins in the ER, or alternatively the removal of such proteins from the Golgi apparatus.
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PMID:Retrieval of HDEL proteins is required for growth of yeast cells. 792 64

The ERD2 gene product in mammalian cells and yeast is a receptor required for protein retention in the endoplasmic reticulum (ER); immunolocalization studies indicate that the protein is concentrated in the cis Golgi. We have identified a homologue of ERD2 in the malaria parasite, Plasmodium falciparum (PfERD2). The deduced protein sequence is 42% identical to mammalian and yeast homologues and bears striking homology in its proposed tertiary structure. PfERD2 is tightly confined to a single focus of staining in the perinuclear region as seen by indirect immunofluorescence. This is redistributed by brefeldin A (BFA) to a diffuse pattern similar to that of parasite BiP, a marker for the ER; removal of the drug results in recovery of the single focus, consistent with the localization of PfERD2 to the parasite Golgi and its participation in a retrograde transport pathway to the ER. Sphingomyelin synthesis is a second resident activity of the cis Golgi whose organization is sensitive to BFA in mammalian cells. Within the parasite it again localizes to a perinuclear region but does not reorganize upon BFA treatment. The results strongly suggest that these two activities are in distinct compartments of the Golgi in the malaria parasite.
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PMID:Identification and localization of ERD2 in the malaria parasite Plasmodium falciparum: separation from sites of sphingomyelin synthesis and implications for organization of the Golgi. 822 85

Electrophysiological experiments have indicated that a fraction of the major auxin-binding protein (ABP1) of maize (Zea mays L.) might be a receptor on the outer surface of the plasma membrane. The predominant location of ABP1 is in the lumen of the endoplasmic reticulum (ER), in accord with its C-terminal KDEL retention signal. Little is known about the biology of the protein in vivo or the rate at which it might pass to the cell surface. We have examined the turnover of ABP1 by in vivo labelling of maize coleoptile sections. After different chase times, ABP1 was immunoprecipitated from detergent-solubilised membrane preparations. Two polypeptides coprecipitated with ABP1. Neither was recognised by any ABP1 antibodies nor by monoclonals to ER retention sequences. The possible significance of these coprecipitating polypeptides is discussed. In addition, we have used a monoclonal antibody to precipitate HDEL proteins from the same membrane preparations. Two dimensional electrophoresis and N-terminal sequencing showed that the major HDEL protein precipitated was a member of the heat-shock-protein 70 family, a homologue of BiP (immunoglobulin-binding protein). We have investigated the turnover of this BiP homologue for comparison with ABP1 and found that both had extended lifetimes, with half-lives greater than 24 h. Use of cordycepin to inhibit transcription indicated that ABP1 mRNA was also long-lived. Synthesis of ABP1 was strongly reduced by heat stress, was reduced a little in response to dithiothreitol and was not markedly changed by tunicamycin. In contrast, BiP synthesis increased markedly in response to tunicamycin and dithiothreitol and increased a little after heat stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of synthesis and turnover of maize auxin-binding protein and observations on its passage to the plasma membrane: comparisons to maize immunoglobulin-binding protein cognate. 858 Jul 60

A DNA fragment containing an open reading frame of 2016 nucleotides has been cloned from the DNA of Aspergillus awamori by hybridization with a probe internal to the KAR2 (BiP) gene of Saccharomyces cerevisiae. The 73.4-kDa-encoded protein showed very high similarity to the endoplasmic reticulum (ER) lumenal BiP protein of S. cerevisiae, Kluyveromyces lactis, Schizosaccharomyces pombe, and animal and plant cells. The BiP protein contains a polar N-terminal end followed by a 18-amino-acid strongly hydrophobic region corresponding to the leader peptide for transport through the ER membrane. In the C-terminal region the protein ends with the HDEL canonical ER retention signal that targets proteins to the lumen of the ER. The A. awamori bip gene contains three introns as shown by cloning and sequencing the putative intron regions from a cDNA library. The bip gene is transcribed as a monocistronic mRNA of 2.4 kb. Two transcription start sites located 160 and 233 bp upstream of the first translated ATG were identified by primer extension. The promoter region showed no consensus TATA box but it contains CCAAT and CreA boxes known to be involved in both stress and carbon-catabolite regulation of fungal promoters.
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PMID:Characterization of the bip gene of Aspergillus awamori encoding a protein with an HDEL retention signal homologous to the mammalian BiP involved in polypeptide secretion. 929 62

The nucleotide sequence of the gene encoding the glucose-regulated protein 78 (GRP78) of Neurospora crassa was determined. The ORF codes for a protein of 662 amino acids (72 kDa) and belongs to the heat shock protein 70 (hsp70) gene family, which is characterized by three HSP70 'signature sequences'. The grp78 gene contains 5 introns. The protein carries the ER retention signal HDEL at its carboxy terminus and is most homologous to the KAR2/GRP78 protein of Saccharomyces cerevisiae (78%) and to KAR2/BiP of Yarrowia lipolytica (76%). The expression of grp78 is constitutive and can be enhanced by starvation, treatment with tunicamycin, the calcium ionophore A23187 or elevated temperatures (40 degrees C). An uninterrupted ORF was found on the reverse cDNA strand of grp78. The putative peptide shows 47% homology to the NAD-specific glutamate dehydrogenase of Achlya klebsiana.
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PMID:Molecular analysis of a glucose-regulated gene (grp78) of Neurospora crassa. 954 20


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