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0GRPE2_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameGRPEL2
DescriptionGrpe protein homolog 2, mitochondrial precursor (mt-grpe#2).
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GON/A
Domain Architecture (Details)
InterPro domains unassigned to SynO:
Molecular chaperones are a diverse family of proteins that function to protect proteins in the intracellular milieu from irreversible aggregation during synthesis and in times of cellular stress. The bacterial molecular chaperone DnaK is an enzyme that couples cycles of ATP binding.ydrolysis.nd ADP release by an N-terminal ATP-hydrolysing domain to cycles of sequestration and release of unfolded proteins by a C-terminal substrate binding domain. In prokaryotes the grpE protein. Dimeric GrpE is the co-chaperone for DnaK.nd acts as a nucleotide exchange factor.timulating the rate of ADP release 5000-fold . DnaK is itself a weak ATPase; ATP hydrolysis by DnaK is stimulated by its interaction with another co-chaperone.naJ. Thus the co-chaperones DnaJ and GrpE are capable of tightly regulating the nucleotide-bound and substrate-bound state of DnaK in ways that are necessary for the normal housekeeping functions and stress-related functions of the DnaK molecular chaperone cycle. The X-ray crystal structure of GrpE in complex with the ATPase domain of DnaK revealed that GrpE is an asymmetric homodimer.ent in a manner that favours extensive contacts with only one DnaKATPase monomer . GrpE does not actively compete for the atomic positions occupied by the nucleotide. GrpE and ADP mutually reduce one anothers affinity for DnaK 200-fold.nd ATP instantly dissociates GrpE from DnaK.
  IPR000740:GrpE nucleotide exchange factor
In prokaryotes.he nucleotide exchange factor GrpE and the chaperone DnaJ are required for nucleotide binding of the molecular chaperone DnaK . The DnaK reaction cycle involves rapid peptide binding and release.hich is dependent upon nucleotide binding. DnaJ accelerates the hydrolysis of ATP by DnaK.hich enables the ADP-bound DnaK to tightly bind peptide. GrpE catalyses the release of ADP from DnaK.hich is required for peptide release. In eukaryotes.rpE is essential for mitochondrial Hsp70 function.owever the cytosolic Hsp70 homologues are GrpE-independent. GrpE binds as a homodimer to the ATPase domain of DnaK.nd may interact with the peptide-binding domain of DnaK. GrpE accomplishes nucleotide exchange by opening the nucleotide-binding cleft of DnaK. GrpE is comprised of two domains.he N-terminal coiled coil domain.hich may facilitate peptide release.nd the C-terminal head domain.hich forms part of the contact surface with the ATPase domain of DnaK. This entry represents the N-terminal coiled-coil domain.
  IPR013805:GrpE nucleotide exchange factor, coiled-coil
In prokaryotes.he nucleotide exchange factor GrpE and the chaperone DnaJ are required for nucleotide binding of the molecular chaperone DnaK . The DnaK reaction cycle involves rapid peptide binding and release.hich is dependent upon nucleotide binding. DnaJ accelerates the hydrolysis of ATP by DnaK.hich enables the ADP-bound DnaK to tightly bind peptide. GrpE catalyses the release of ADP from DnaK.hich is required for peptide release. In eukaryotes.rpE is essential for mitochondrial Hsp70 function.owever the cytosolic Hsp70 homologues are GrpE-independent. GrpE binds as a homodimer to the ATPase domain of DnaK.nd may interact with the peptide-binding domain of DnaK. GrpE accomplishes nucleotide exchange by opening the nucleotide-binding cleft of DnaK. GrpE is comprised of two domains.he N-terminal coiled coil domain.hich may facilitate peptide release.nd the C-terminal head domain.hich forms part of the contact surface with the ATPase domain of DnaK. The head domain is comprised of six short beta strands with a limited hydrophobic core.
  IPR009012:GrpE nucleotide exchange factor, head
IPR000740:GrpE 
Evalue:-41.4559326171875 
Location:37-219
SequencesProtein: GRPE2_HUMAN (225 aa)
mRNA: NM_152407
Local Annotation
Synapse Ontology
mitochondria are frequently observed in the vicinity of the synaptic vesicle clusters, in agreement with the ATP requirement of several steps of the vesicle cycle.
sdb:0118 mitochondria  (Evidence:keywords)
KO assignmentK03687
  Level 3 annotation:
    molecular chaperone GrpE
  Level 2 annotation:
    Protein folding and associated processing
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 30 residues, 148705284-148705372Exon2: 53 residues, 148708027-148708181Exon3: 29 residues, 148709409-148709491Exon4: 1223 residues, 148710673-148714338Exon5: 2 residues, -Jump to GRPE2_HUMAN  
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Loci Cluster (Details)Loci: 3499 148185000-148188447 ~-3K 29722(ADRB2)(+)Loci: 4741 148364376-148422880 ~-59K 29724(SH3TC2)(-)Loci: 3500 148705284-148714338 ~-9K 29730(GRPEL2)(+)Loci: 4742 148855037-148911200 ~-56K 29736(CSNK1A1)(-)Loci: 4740 147841291-148013909 ~-173K 29718(HTR4)(-)Link out to UCSC