|Protein Name||78 kDa glucose-regulated protein|
|Ref Sequence ID||NP_001068616.1|
|Protein Existence Status||Reviewed: Experimental evidence at transcript level|
|Protein Function||immunoglobulin heavy chain binding protein1 and as the glucose regulated protein; ER-located member of the family of HSP70 molecular chaperones; binds transiently to newly-synthesized proteins in the ER and more permanently to misfolded,underglycosylated or unassembled proteins whose transport from the ER is blocked; assists the folding and assembly of newly-synthesized proteins by recognising unfolded polypeptides and,by inhibiting intra- or intermolecular aggregation,maintaining them in a state competent for subsequent folding and oligomerisation; maintain the permeability barrier of the ER membrane by sealing the lumenal end of the translocon pore before and early in translocation; required during ara cell mating for the stage of karyogamy that involves fusion of the nuclear membranes of Saccharomyces cerevisiae. BiP is an essential component of the translocation machinery for protein import into the ER, a regulator for Ca2+ homeostasis in the ER, as well as a facilitator of ER-associated protein degradation (ERAD) via retrograde transportation of aberrant proteins across the ER membrane.|
|Biochemical Properties||BiP does not interact with native polypeptides; two major domains, an N-terminal domain that contains the ATPase catalytic site and a C-terminal substrate bind- ing domain; domains communicate to regulate the affinity and duration of poly.peptide binding; In vitro, BiP can interact with short synthetic peptides whose binding stimulates its ATPase activity and alters its oligomeric state; interacts with sequences normally located in the interior of a fully-folded protein; presence of a heptameric motif with a bulky aromatic or hydrophobic residue most frequently tryptophan, phenylalanine or leucine, but also methionine and isoleucine.|
|Significance in milk||required for mammary gland development; contributes to the regulation of Cripto signaling in mammary stem cells; . Grp78 heterozygosity impeded transgene-induced mammary tumor development, with the tumors showing reduced proliferation, increased apoptosis, and dramatic reduction of tumor angiogenesis|
|PTMs||mammalian BiP exists in interconvertible monomeric and oligomeric forms and can be post-translationally modified by phosphorylation and by ADP ribosylation|
| Site(s) of PTM(s) |
|Predicted Disorder Regions||1-25,635-655|
|TM Helix Prediction||No TM helices|
|Significance of PTMs||important in regulating the synthesis and polypeptide binding activity of the molecule; conditions that increase the levels of unfolded polypeptides in the ER lumen cause a decrease in the extent of modification of BiP and an increase in the proportion of monomeric species; post-translational modification of BiP appears to provide a storage pool of BiP that can be recruited back to the active form in response to need|
|Additional Comments||BiP is expressed in arginine vasopressin (AVP) neurons under non-stress conditions and that BiP expression is upregulated in proportion to the increased AVP expression under dehydration.|
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