Protein: Endoplasmic reticulum chaperone BiP (EC 3.6.4.10) (78 kDa glucose-regulated protein) (GRP-78) (Binding-immunoglobulin protein) (BiP) (Heat shock protein 70 family protein 5) (HSP70 family protein 5) (Heat shock protein family A member 5) (Immunoglobulin heavy chain-binding protein) (P20029)
Organism: Mus musculus (Mouse)
Function: Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen. Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate. Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (By similarity).
Subcellular location: Endoplasmic reticulum lumen {ECO:0000255|PROSITE-ProRule:PRU10138, ECO:0000269|PubMed:21992152}. Melanosome {ECO:0000250|UniProtKB:P11021}. Cytoplasm {ECO:0000269|PubMed:21992152}. Cell surface. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV (By similarity). Localizes to the cell surface in epithelial cells; high levels of free iron promotes cell surface localization (By similarity). {ECO:0000250|UniProtKB:P11021}.
Sequence: MMKFTVVAAALLLLGAVRAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNRITPSYVAFTPEGERLIGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVVEKKTKPYIQVDIGGGQTKTFAPEEISAMVLTKMKETAEAYLGKKVTHAVVTVPAYFNDAQRQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDLGGGTFDVSLLTIDNGVFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALSSQHQARIEIESFFEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIVLVGGSTRIPKIQQLVKEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVCPLTLGIETVGGVMTKLIPRNTVVPTKKSQIFSTASDNQPTVTIKVYEGERPLTKDNHLLGTFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKITITNDQNRLTPEEIERMVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEEKIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSGGPPPTGEEDTSEKDEL
InterPro domains: - IPR029048: Heat shock protein 70kD, C-terminal domain superfamily (homologous_superfamily) [561-643]
- IPR042050: Endoplasmic reticulum chaperone BIP, nucleotide-binding domain (domain) [29-406]
- IPR013126: Heat shock protein 70 family (family) [31-636]
- IPR018181: Heat shock protein 70, conserved site (conserved_site) [34-374]
- IPR029047: Heat shock protein 70kD, peptide-binding domain superfamily (homologous_superfamily) [410-567]
- IPR043129: ATPase, nucleotide binding domain (homologous_superfamily) [29-408]
Interaction partners: - Serine/threonine-protein kinase/endoribonuclease IRE1
- Endoplasmin
- Hypoxia up-regulated protein 1
- Cyclic AMP-dependent transcription factor ATF-6 alpha
- Mesencephalic astrocyte-derived neurotrophic factor
- Protein disulfide-isomerase A3
- DnaJ homolog subfamily B member 11
- Calreticulin
- Eukaryotic translation initiation factor 2-alpha kinase 3
- Protein disulfide-isomerase A6
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140657 (ATP-dependent activity), GO:0016887 (ATP hydrolysis activity), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0016817 (hydrolase activity, acting on acid anhydrides), GO:0016818 (hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides), GO:0016462 (pyrophosphatase activity), GO:0017111 (ribonucleoside triphosphate phosphatase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0022414 (reproductive process), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0019953 (sexual reproduction), GO:0048869 (cellular developmental process), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0055085 (transmembrane transport), GO:0019222 (regulation of metabolic process), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0032504 (multicellular organism reproduction), GO:0003006 (developmental process involved in reproduction), GO:0009056 (catabolic process), GO:0033036 (macromolecule localization), GO:0044237 (cellular metabolic process), GO:0022412 (cellular process involved in reproduction in multicellular organism), GO:0006457 (protein folding), GO:0009893 (positive regulation of metabolic process), GO:0065009 (regulation of molecular function), GO:0048609 (multicellular organismal reproductive process), GO:0044238 (primary metabolic process), GO:0007276 (gamete generation), GO:0007281 (germ cell development), GO:0050790 (regulation of catalytic activity), GO:0044093 (positive regulation of molecular function), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0044248 (cellular catabolic process), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0048515 (spermatid differentiation), GO:0044255 (cellular lipid metabolic process), GO:0051649 (establishment of localization in cell), GO:0060255 (regulation of macromolecule metabolic process), GO:0051668 (localization within membrane), GO:0043170 (macromolecule metabolic process), GO:0007283 (spermatogenesis), GO:0045184 (establishment of protein localization), GO:0006629 (lipid metabolic process), GO:0046907 (intracellular transport), GO:0010941 (regulation of cell death), GO:0071806 (protein transmembrane transport), GO:0006810 (transport), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0070727 (cellular macromolecule localization), GO:0016043 (cellular component organization), GO:0080090 (regulation of primary metabolic process), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0071705 (nitrogen compound transport), GO:0051246 (regulation of protein metabolic process), GO:0010256 (endomembrane system organization), GO:0051336 (regulation of hydrolase activity), GO:0072594 (establishment of protein localization to organelle), GO:0030163 (protein catabolic process), GO:0071702 (organic substance transport), GO:0065002 (intracellular protein transmembrane transport), GO:0007286 (spermatid development), GO:0090150 (establishment of protein localization to membrane), GO:0034976 (response to endoplasmic reticulum stress), GO:0009057 (macromolecule catabolic process), GO:0006886 (intracellular protein transport), GO:0007399 (nervous system development), GO:0044265 (cellular macromolecule catabolic process), GO:0015031 (protein transport), GO:0051247 (positive regulation of protein metabolic process), GO:0030258 (lipid modification), GO:0008104 (protein localization), GO:0043085 (positive regulation of catalytic activity), GO:0006996 (organelle organization), GO:0048232 (male gamete generation), GO:0072657 (protein localization to membrane), GO:0072655 (establishment of protein localization to mitochondrion), GO:0007005 (mitochondrion organization), GO:0033365 (protein localization to organelle), GO:0042981 (regulation of apoptotic process), GO:0006612 (protein targeting to membrane), GO:0030162 (regulation of proteolysis), GO:0072599 (establishment of protein localization to endoplasmic reticulum), GO:0052547 (regulation of peptidase activity), GO:0008637 (apoptotic mitochondrial changes), GO:0048285 (organelle fission), GO:0150063 (visual system development), GO:0006605 (protein targeting), GO:0045862 (positive regulation of proteolysis), GO:0019395 (fatty acid oxidation), GO:0048699 (generation of neurons), GO:0051345 (positive regulation of hydrolase activity), GO:0006626 (protein targeting to mitochondrion), GO:0031401 (positive regulation of protein modification process), GO:0070585 (protein localization to mitochondrion), GO:0010952 (positive regulation of peptidase activity), GO:0052548 (regulation of endopeptidase activity), GO:0010466 (negative regulation of peptidase activity), GO:0070972 (protein localization to endoplasmic reticulum), GO:0030225 (macrophage differentiation), GO:0010950 (positive regulation of endopeptidase activity), GO:2000116 (regulation of cysteine-type endopeptidase activity), GO:2001056 (positive regulation of cysteine-type endopeptidase activity), GO:0043281 (regulation of cysteine-type endopeptidase activity involved in apoptotic process), GO:0043280 (positive regulation of cysteine-type endopeptidase activity involved in apoptotic process), GO:0006919 (activation of cysteine-type endopeptidase activity involved in apoptotic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0031974 (membrane-enclosed lumen), GO:0048471 (perinuclear region of cytoplasm), GO:0030054 (cell junction), GO:0031984 (organelle subcompartment), GO:0030496 (midbody), GO:0031975 (envelope), GO:0005615 (extracellular space), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005576 (extracellular region), GO:0031090 (organelle membrane), GO:0031967 (organelle envelope), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0016528 (sarcoplasm), GO:0043230 (extracellular organelle), GO:0098827 (endoplasmic reticulum subcompartment), GO:0042175 (nuclear outer membrane-endoplasmic reticulum membrane network), GO:0005739 (mitochondrion), GO:0043233 (organelle lumen), GO:0005783 (endoplasmic reticulum), GO:0070161 (anchoring junction), GO:0070062 (extracellular exosome), GO:0043227 (membrane-bounded organelle), GO:0030055 (cell-substrate junction), GO:0005740 (mitochondrial envelope), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0065010 (extracellular membrane-bounded organelle), GO:0005789 (endoplasmic reticulum membrane), GO:0031982 (vesicle), GO:0070013 (intracellular organelle lumen), GO:0031966 (mitochondrial membrane), GO:0005925 (focal adhesion), GO:1903561 (extracellular vesicle), GO:0097708 (intracellular vesicle), GO:0005634 (nucleus)