Any feedback?
Information on EC 7.4.2.3 - mitochondrial protein-transporting ATPase
for references in articles please use BRENDA:EC7.4.2.3Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
7.4.2.3 mitochondrial protein-transporting ATPaseIUBMB Comments
A non-phosphorylated, non-ABC (ATP-binding cassette) ATPase involved in the transport of proteins or preproteins into mitochondria using the TIM protein complex. TIM is the protein transport machinery of the mitochondrial inner membrane that contains three essential Tim proteins: Tim17 and Tim23 are thought to build a preprotein translocation channel while Tim44 interacts transiently with the matrix heat-shock protein Hsp70 to form an ATP-driven import motor.
Specify your search results
Word Map
- 7.4.2.3
- hsp90
- drosophila
- proteasome
-
misfolded
-
co-chaperone
- necrosis
-
cytoprotective
- dismutase
-
heat-induced
-
refolding
- lymphocyte
- neurodegenerative
- ischemia
-
stressor
- cerebral
- bcl-2
- dnaj
- artery
-
thermotolerance
- melanogaster
- caspase-3
-
client
-
neuroprotective
- hyperthermia
- sod
- tnf
-
preconditioning
- larvae
-
insult
-
reperfusion
- cadmium
- gill
- hypoxia
-
anti-apoptotic
- malondialdehyde
-
proteostasis
-
polyglutamine
- geldanamycin
- preproteins
-
tetratricopeptide
-
shock-induced
- prion
- quercetin
- flies
-
glucose-regulated
- c-fos
-
disaggregation
- medicine
-
immunophilins
-
intermembrane
- cryptosporidium
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
hsp70, hsp70 chaperone, tom complex, mthsp70, mitochondrial hsp70, dnak chaperone, protein translocase, mhsp70, hsp70 atpase, pam18, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 3.6.3.51
-
-
formerly
-
Hsc70 ATPase
Hsp70
inner mitochondrial membrane preprotein translocase
-
-
-
-
mitochondrial hsp70
mitochondrial presequence translocase
-
the translocase operates in three stages, outer-membrane-tethering, inner-membrane-sorting, matrix-translocation, at each stage, the translocase is coupled to a different partner
mitochondrial protein-transporting ATPase
mtHSP70
Ssc1
TIM protein complex
Tim23 channel
-
a protein in transit across the Tim23 channel requires help in order to be imported completely, this step is catalyzed by the translocation motor that is formed by the ATP-hydrolyzing mHsp70, Tim14, Tim16 and Mge1
TOM complex
-
the core complex contains five different subunits, Tom40, Tom22, Tom7, Tom6, Tom5
TOM protein complex
translocase of the mitochondrial outer membrane
additional information
-
the enzyme belongs to the chaperones of the 70-kDa family, Hsp70
mitochondrial hsp70
-
-
mtHSP70
-
-
TIM protein complex
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + H2O + mitochondrial-protein[side 1] = ADP + phosphate + mitochondrial-protein[side 2]
ATP + H2O + mitochondrial-protein[side 1] = ADP + phosphate + mitochondrial-protein[side 2]
a non-phosphorylated, non-ABC (ATP-binding cassette) ATPase involved in the transport of proteins or preproteins into mitochondria using the TIM protein complex. (TIM is the protein transport machinery of the inner mitochondrial membrane that contains three essential Tim proteins: Tim17 and Tim23 are thought to build a preprotein translocation channel while Tim44 interacts transiently with the matrix heat-shock protein Hsp70 to form an ATP-driven import motor.)
-
-
-
ATP + H2O + mitochondrial-protein[side 1] = ADP + phosphate + mitochondrial-protein[side 2]
model for efficient translocation across the mitochondrial inner membrane through regulated interactions
-
ATP + H2O + mitochondrial-protein[side 1] = ADP + phosphate + mitochondrial-protein[side 2]
the mitochondrial Hsp70 chaperone Ssc1 requires the Hsp70 escort protein Hep1, an L-shaped matrix protein with a zinc finger motif
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
transmembrane transport
hydrolysis of phosphoric ester
-
-
-
-
transmembrane transport
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
ATP phosphohydrolase (mitochondrial protein-importing)
A non-phosphorylated, non-ABC (ATP-binding cassette) ATPase involved in the transport of proteins or preproteins into mitochondria using the TIM protein complex. TIM is the protein transport machinery of the mitochondrial inner membrane that contains three essential Tim proteins: Tim17 and Tim23 are thought to build a preprotein translocation channel while Tim44 interacts transiently with the matrix heat-shock protein Hsp70 to form an ATP-driven import motor.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
9000-83-3
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + dihydrofolate reductase[side 1]
ADP + phosphate + dihydrofolate reductase[side 2]
-
-
-
-
?
ATP + H2O + heat shock protein 70[side 1]
ADP + phosphate + heat shock protein 70[side 2]
-
-
-
-
?
ATP + H2O + heat shock protein 90[side 1]
ADP + phosphate + heat shock protein 90[side 2]
-
-
-
-
?
ATP + H2O + mitochondrial preprotein pFAD[side 1]
ADP + phosphate + mitochondrial preprotein pFAD[side 2]
-
-
-
-
?
ATP + H2O + mitochondrial-protein[side 1]
ADP + phosphate + mitochondrial-protein[side 2]
-
-
-
-
?
ATP + H2O
ADP + phosphate
-
ATP hydrolysis needed by Bcl-2 associated athanogene 1M (Bag-1M), which interacts with the ATPase domain of Hsp70 to modulate the release of the substrate from Hsp70. ATP hydrolysis enhances Bag-1M-mediated inhibition of the DNA binding by the glucocorticoid receptor GR
-
-
?
ATP + H2O
ADP + phosphate
-
several rounds of ATP-dependent binding to and release from mtHsp70 lead to complete translocation of polypeptides into the mitochondrial matrix
-
-
?
ATP + H2O
ADP + phosphate
-
Hsp70 escort proteins are essential for maintaining the function of yeast mitochondrial hsp70 molecular chaperones(mtHsp70)
-
-
?
ATP + H2O
ADP + phosphate
-
mtHsp70 exhibits limited solubility due to aggregation mediated by its ATPase domain, residues 47-440, but human escort protein Hep directly enhances chaperone solubility through interactions with this domain
-
-
?
ATP + H2O
ADP + phosphate
-
human mtHsp70 exhibits limited solubility due to aggregation mediated by its ATPase domain and show that human Hep directly enhances chaperone solubility through interactions with this domain
-
-
?
ATP + H2O
ADP + phosphate
-
the human escort protein Hep binds to the ATPase domain, residues 47-440, of mitochondrial Hsp70 and regulates ATP hydrolysis
-
-
?
ATP + H2O
ADP + phosphate
-
binding of the client proteins to the SBD, substrate binding domain of the mtHsp70 brings a global change in the ATPase domain, thus enhancing the rate of ATP hydrolysis of Hsp70
-
-
?
ATP + H2O
ADP + phosphate
-
the concerted action of Tim44 and matrix-heat-shock protein Hsp70 drives unfolding of preproteins and accelerates translocation of loosely folded preproteins. While mtHsp70 is essential for import of both tightly and loosely folded preproteins, Tim44 plays a more specialized role in translocation of tightly folded domains
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
activity of mtHsp70 higher than that of DnaK
-
-
?
ATP + H2O
ADP + phosphate
-
ATP appears more favourable for mtHsp70 binding to GST-Tim15 than ADP, ruling out that GST-Tim15 is non-specifically trapped by mtHsp70 as an unfolded chaperone substrate
-
-
?
ATP + H2O
ADP + phosphate
-
the essential mitochondrial Hsp70 is required for the import of mitochondrial preproteins into the matrix compartment. The translocation, specific activity of mitochondrial Hsp70 is coordinated by its interaction with specific partner proteins, forming the import motor complex that provides the energy for unfolding and complete translocation of precursor polypeptide chains. Impaired interdomain communication in mitochondrial Hsp70 results in the loss of inward-directed translocation force
-
-
?
ATP + H2O
ADP + phosphate
-
Hsp70-type chaperones show nucleotide-regulated affinity to polypeptide substrates, allosteric regulation in the course of preprotein translocation. Import of radio-labeled preprotein b2-DHFR fusion protein
-
-
?
ATP + H2O
ADP + phosphate
-
preprotein import-driving ATPase activity of mtHsp70
-
-
?
ATP + H2O
ADP + phosphate
-
ATP appears more favourable for mtHsp70 binding to GST-Tim15 than ADP, ruling out that GST-Tim15 is non-specifically trapped by mtHsp70 as an unfolded chaperone substrate
-
-
?
ATP + H2O + protein/out
ADP + phosphate + protein/in
-
mitochondrial preproteins synthesized in the cytosol are imported through the mitochondrial outer membrane by the translocase of the outer mitochondrial membrane, TOM, complex
-
-
ir
ATP + H2O + protein/out
ADP + phosphate + protein/in
-
Tim14 and Tim16 are essential components of the import motor of the mitochondrial TIM23 preprotein translocase, the J and J-like domains of Tim14 and 16 function in the regulation of the ATPase activity of the Hsp70 chaperone of the import motor, with the help of Tim44, Tim14, Tim16 and Mge1 mtHsp70 converts the energy of ATP hydrolysis into vectorial movement of the unfolded polypeptide chain across the translocation pore
-
-
ir
additional information
?
-
-
escort proteins regulate the catalytic activity and solubility of their cognate chaperones, and both forms of regulation arise from interactions with the mtHsp70 ATPase domain, residues 47-440
-
-
?
additional information
?
-
-
newly synthesized mitochondrial precursor proteins have to become unfolded by the mitochondrial Hsp70 import motor to cross the mitochondrial membranes, unfolding mechanism, overview
-
-
?
additional information
?
-
-
an essential peripheral membrane protein, Tim44, tethers mtHsp70, the core of the import motor, to the translocon. The presequence translocase-associated motor complex, PAM, acts as a functional unit to couple the action of mitochondrial Hsp70 chaperone Ssc1 to the movement of preproteins through the Tim23 translocon into the mitochondrial matrix. Tim44-mtHsp70 interaction is destabilized by binding of mtHsp70 to a substrate polypeptide. The N-terminal 167-amino-acid segment of mature Tim44 is suf?cient for both interaction with mtHsp70 and destabilization of a Tim44-mtHsp70 complex caused by client protein binding, mutational interaction analysis, overview
-
-
?
additional information
?
-
-
even a partial disruption of the interdomain communication in the mtHsp70 chaperone results in an almost complete breakdown of its translocation-driving properties
-
-
?
additional information
?
-
-
interaction of mtHsp70 with partner proteins Mdj1, Mge1, and Tim44
-
-
?
additional information
?
-
-
the active presequence translocase drives motor-dependent mitochondrial protein translocation
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + H2O + heat shock protein 70[side 1]
ADP + phosphate + heat shock protein 70[side 2]
-
-
-
-
?
ATP + H2O + mitochondrial-protein[side 1]
ADP + phosphate + mitochondrial-protein[side 2]
-
-
-
-
?
ATP + H2O
ADP + phosphate
-
Hsp70 escort proteins are essential for maintaining the function of yeast mitochondrial hsp70 molecular chaperones(mtHsp70)
-
-
?
ATP + H2O
ADP + phosphate
-
mtHsp70 exhibits limited solubility due to aggregation mediated by its ATPase domain, residues 47-440, but human escort protein Hep directly enhances chaperone solubility through interactions with this domain
-
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
preprotein transport across the mitochondrial inner membrane
-
?
ATP + H2O
ADP + phosphate
-
the essential mitochondrial Hsp70 is required for the import of mitochondrial preproteins into the matrix compartment. The translocation, specific activity of mitochondrial Hsp70 is coordinated by its interaction with specific partner proteins, forming the import motor complex that provides the energy for unfolding and complete translocation of precursor polypeptide chains. Impaired interdomain communication in mitochondrial Hsp70 results in the loss of inward-directed translocation force
-
-
?
ATP + H2O
ADP + phosphate
-
preprotein import-driving ATPase activity of mtHsp70
-
-
?
ATP + H2O + protein/out
ADP + phosphate + protein/in
-
mitochondrial preproteins synthesized in the cytosol are imported through the mitochondrial outer membrane by the translocase of the outer mitochondrial membrane, TOM, complex
-
-
ir
ATP + H2O + protein/out
ADP + phosphate + protein/in
-
Tim14 and Tim16 are essential components of the import motor of the mitochondrial TIM23 preprotein translocase, the J and J-like domains of Tim14 and 16 function in the regulation of the ATPase activity of the Hsp70 chaperone of the import motor, with the help of Tim44, Tim14, Tim16 and Mge1 mtHsp70 converts the energy of ATP hydrolysis into vectorial movement of the unfolded polypeptide chain across the translocation pore
-
-
ir
additional information
?
-
-
escort proteins regulate the catalytic activity and solubility of their cognate chaperones, and both forms of regulation arise from interactions with the mtHsp70 ATPase domain, residues 47-440
-
-
?
additional information
?
-
-
newly synthesized mitochondrial precursor proteins have to become unfolded by the mitochondrial Hsp70 import motor to cross the mitochondrial membranes, unfolding mechanism, overview
-
-
?
additional information
?
-
-
an essential peripheral membrane protein, Tim44, tethers mtHsp70, the core of the import motor, to the translocon. The presequence translocase-associated motor complex, PAM, acts as a functional unit to couple the action of mitochondrial Hsp70 chaperone Ssc1 to the movement of preproteins through the Tim23 translocon into the mitochondrial matrix. Tim44-mtHsp70 interaction is destabilized by binding of mtHsp70 to a substrate polypeptide. The N-terminal 167-amino-acid segment of mature Tim44 is suf?cient for both interaction with mtHsp70 and destabilization of a Tim44-mtHsp70 complex caused by client protein binding, mutational interaction analysis, overview
-
-
?
additional information
?
-
-
even a partial disruption of the interdomain communication in the mtHsp70 chaperone results in an almost complete breakdown of its translocation-driving properties
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
the presequence-cleaved mature forms of the recombinant fusion proteins with a 50 or 60 residue spacer sequence are proteinase K-resistant, whereas those with a 70 or 80 residue spacer sequence are proteinase K-sensitive
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
DnaJ
-
bacterial co-chaperone stimulates ATPase activity of mtHsp70 5fold, that of DnaK 20fold
-
fluorescein-CALLQSRLLLSAPRRAAATARY
-
similar affininty of mtHsp70 and Dnak at 25°C
GrpE
-
bacterial co-chaperone stimulates ATPase activity of mtHsp70 5fold, that of DnaK 20fold
-
GrpEL1
-
the proposed nucleotide exchange factor of the human mtHsp70 machine. To access the nucleotide relase of human GrpEL1, a single turnover ATPase assay is performed to monitor the hydrolysis of the prebound mtHsp70-ATP complex of the wild-type protein in the presence of GrpEL1. Human GrpEL1 shows robust nucleotide exchange activity in the presence of excess unlabeled ATP, thus inhibiting the maximum ATP hydrolysis of wild-type mtHsp70
-
human escort protein
-
Hep, stimulates the activity of mtHsp70 49fold, and also 11.5fold the activity of the isolated ATPase domain. Hep binding to full-length mtHsp70 and its isolated ATPase domain is strongest in the absence of nucleotides
-
human Hsp70 escort protein
-
human Hsp70 escort protein (Hep) possesses the unique ability to stimulate the ATPase activity of mtHsp70 as well as to prevent the aggregation of unfolded client proteins similar to J-proteins
-
J-protein
-
J-protein splice hTid-1L, larger isoform and hTid-1S, smaller isoform. At a morlar ratio of mtHsp70 to J-protein, a 3.2fold stimulation is observed with hTid-1L for wild-type protein. hTid-1S shows an 11fold stimulation for wild-type mtHp70
-
KCCC
-
comparable stimulation of ATPase activity of mtHsp70 and Dnak
-
KKCC
-
comparable stimulation of ATPase activity of mtHsp70 and Dnak
-
Mdj1p
-
mitochondrial co-chaperone stimulates ATPase activity of both mtHsp70 and Dnak 5-6fold, 20fold activation can be achieved by different molar ratios
-
Mdj2
-
stimulates ATPase activity of mtHsp70 to the same extent as TIM14, forms a complex with TIM16, which does not interfer with the TIM16-TIM14 complex and cannot support cell growth, but overexpression of Mdj2 fully restores growth of cells lacking TIM14
-
Mge1p
-
mitochondrial co-chaperone stimulates ATPase activity of both mtHsp70 and Dnak 5-6fold, 20fold activation can be achieved by different molar ratios
-
NRLLLTG
-
substrate binding allosterically stimulates ATPase activity of mtHsp70 2.5 fold, that of Dnak 5fold
Pam18
-
stimulates mtHsp70's ATPase activity, Pam18 is less active in complex with Pam16, which is not sufficient to have significant effects on mitochondrial protein import or cell growth
-
TIM14
-
stimulates ATPase activity of mtHsp70 and thereby enables efficient binding of mtHsp70 to incoming preproteins, stimulates to the same extent as Mdj2, forms a complex with TIM16, which recruits it to the translocase, the TIM16-TIM14 complex does not interfer with the TIM16-Mdj2 complex
-
TIM14
-
stimulates ATPase activity of mtHsp70, forms a complex with the J-like protein TIM16, which regulates the J cochaperone activity of TIM14
-
additional information
-
Pam16 is unable to stimulate mtHsp70's ATPase activity
-
additional information
-
the soluble co-chaperone Mge1 stimulates ADP/ATP exchange
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
quantitative analysis of ATP binding activity of recombinant mtHsp70
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 76.2
-
mtHsp70 binding kinetics are faster at higher temperatures
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
the mitochondrial heat shock protein 70, mtHsp70 machinery components are highly conserved among eukaryotes, including humans
-
-
brenda
-
210436, 210437, 210438, 210439, 210440, 210441, 656108, 656243, 656858, 668549, 672943, 672993, 673327, 674522, 675002, 675964, 676134, 676773, 686245, 687560, 689911, 698945, 700155
-
-
brenda
subunit of presequence translocase-associated motor PAM
-
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
TIG-1 cell, overexpression of mortalin extends the in vitro lifespan of the fibroblasts
brenda
additional information
-
NARF cell, stably transfected with isopropyl beta-D-thiogalactoside-inducible p14ARF
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
cpHsc70-1 and cpHsc70-2 are highly conserved proteins, imported into chloroplasts, analyzed by fluorescence microscopy
brenda
-
YFP-fusion proteins of cpHsc70-1 and cpHsc70-2 are predominantly stromal, analyzed by fluorescence microscopy
brenda
-
low level, analyzed by fluorescence microscopy
brenda
additional information
-
in vitro import of the fusion proteins depends on Gly repeat lengths and folded mature domains. Presequence and Gly repeat function as an mtHsp70 binding site and mtHsp70 avoidance segment, respectively
brenda
-
to study the biochemical functions the components of the mtHsp70 machinery, Hsp70, J-protein, GrpE, and Hep are reconstituted
brenda
-
-
brenda
-
inner mitochondrial membrane
brenda
additional information
-
after expression in yeast, enzyme with presequence of ATPase subunit 9 of Neurospora crassa is targeted to the matrix of mitochondria and interacts in ATP-independent manner with Tim44
-
brenda
additional information
-
mitosomes, despite their advanced state of reductive evolution have retained vestiges of presequence-dependent and -independent protein import pathways akin to those that operate in mammalian mitochondria. Targeting mtHsp70 into mitosomes no longer requires cleavable presequences, a derived feature from their mitochondrial homologues
-
brenda
additional information
Giardia intestinalis WB / CC 30957
-
mitosomes, despite their advanced state of reductive evolution have retained vestiges of presequence-dependent and -independent protein import pathways akin to those that operate in mammalian mitochondria. Targeting mtHsp70 into mitosomes no longer requires cleavable presequences, a derived feature from their mitochondrial homologues
-
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
temperature-sensitive mutants of mitochondrial Hsp70, affected in either ATP-binding and hydrolysis or Tim44 interaction, display defects in matrix protein import and concomitant TOM/TIM23-supercomplex formation when import reactions were performed under non-permissive conditions
metabolism
-
for the ATP-dependent translocation of preproteins into the aqueous matrix, TIM23CORE cooperates with the presequence translocase-associated import motor (PAM) that is composed of mitochondrial heat shock protein 70 (mtHsp70) and five co-chaperones that differentially regulate the import-driving ATPase activity of mtHsp70 and the assembly status of PAM: Tim44, Pam16, Pam17, Pam18, and Mge1. The biogenesis of presequence-carrying polytopic inner membrane proteins requires a close cooperation of the TIM23/PAM machinery with the export translocase Oxa1. Therefore, the TIM23 complex acts as an intricate multipurpose molecular machine in which the coupling of distinct partner proteins to TIM23CORE generates functional specificity
physiological function
additional information
-
quantitative analysis of mitochondrial protein complexes, overview
physiological function
-
in mitochondria, matrix translocation of polypeptides depends on the ATP-powered mitochondrial Hsp70 (mtHsp70), the catalytic constituent of the presequence translocase-associated motor (PAM), at the trans side of the protein-conducting channel. mtHsp70 exists in a soluble pool mediating matrix protein folding and a TIM23-associated pool generating precursor velocity over the inner membrane. During precursor transport, a translocation intermediate is established in which the motor-associated, unfolded precursor simultaneously spans the TOM and TIM23 complexes thereby generating a mitochondrial contact site. For both activities, the soluble co-chaperone Mge1 stimulates ADP/ATP exchange. To drive precursor translocation, the Hsp70-import motor associates with the protein-conducting channel of the TIM23 complex, the ATPase cycle of Hsp70 is regulated in the context of a translocating polypeptide chain. The presence of all Hsp70 co-chaperones at the import channel is not sufficient to promote matrix protein import, instead a recharging of the active translocase with Pam18 is required for motor activity. Thus, a replenishment cycle of co-chaperones at the TIM23 complex is an integral part of Hsp70s ATPase cycle at the channel exit site and essential to maintain motor-driven mitochondrial protein import. The association of the membrane-bound co-chaperones with the Tim23 channel unit is a prerequisite for the spatially controlled mtHsp70 regulation in mitochondria. Pam18 needs to be recharged at the translocase in order to maintain progressive mtHsp70 activity, such a replenishment cycle of the translocases co-chaperone Pam18 drives the ATP hydrolysis of the import motor in the precursor-occupied translocase and thus precursor transport along the presequence pathway, overview
physiological function
-
the protein transports heat shock protein 70 into the nucleus to protect cellular homeostasis against heat shock
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). B4NCW8_DROWI
135
0
15503
TrEMBL
Mitochondrion (Reliability: 3)
A0A0B2QYD7_GLYSO
473
0
54394
TrEMBL
Mitochondrion (Reliability: 1)
B4M4X3_DROVI
224
0
24203
TrEMBL
other Location (Reliability: 3)
A0A0B2RFQ0_GLYSO
93
0
10877
TrEMBL
other Location (Reliability: 3)
B4NYA8_DROYA
177
2
18083
TrEMBL
other Location (Reliability: 2)
B3N5Z2_DROER
177
2
18071
TrEMBL
other Location (Reliability: 2)
B4KCL8_DROMO
223
3
24141
TrEMBL
other Location (Reliability: 3)
B5DJL9_DROPS
171
2
17798
TrEMBL
other Location (Reliability: 2)
B3NTT3_DROER
151
0
16711
TrEMBL
Secretory Pathway (Reliability: 5)
B4L6B0_DROMO
171
0
18261
TrEMBL
Mitochondrion (Reliability: 4)
B4PNQ8_DROYA
222
1
24212
TrEMBL
other Location (Reliability: 2)
B4PV79_DROYA
179
0
18738
TrEMBL
other Location (Reliability: 2)
B3M179_DROAN
184
2
19797
TrEMBL
other Location (Reliability: 2)
A0A0J9R3N3_DROSI
177
2
18356
TrEMBL
other Location (Reliability: 2)
B3M175_DROAN
224
1
24384
TrEMBL
other Location (Reliability: 2)
A0A0B2SQD8_GLYSO
175
2
19102
TrEMBL
other Location (Reliability: 3)
B4NB99_DROWI
135
0
15213
TrEMBL
other Location (Reliability: 3)
B4K5Q1_DROMO
138
0
15383
TrEMBL
other Location (Reliability: 4)
A0A0R1E0S2_DROYA
191
0
20247
TrEMBL
other Location (Reliability: 2)
B5DMT4_DROPS
127
0
14343
TrEMBL
Mitochondrion (Reliability: 2)
B4PZ13_DROYA
185
1
18934
TrEMBL
other Location (Reliability: 2)
B3M396_DROAN
142
0
15763
TrEMBL
Mitochondrion (Reliability: 5)
M2XWH6_GALSU
349
0
40515
TrEMBL
Mitochondrion (Reliability: 2)
B3NYB7_DROER
186
1
19073
TrEMBL
other Location (Reliability: 2)
B3ML85_DROAN
206
0
21983
TrEMBL
other Location (Reliability: 2)
B4PRI4_DROYA
141
0
15793
TrEMBL
Mitochondrion (Reliability: 5)
B4LX95_DROVI
139
0
15537
TrEMBL
other Location (Reliability: 4)
B5DN15_DROPS
191
1
20546
TrEMBL
other Location (Reliability: 3)
B4Q0S2_DROYA
157
0
17145
TrEMBL
Secretory Pathway (Reliability: 4)
B4MAF7_DROVI
135
0
15294
TrEMBL
Mitochondrion (Reliability: 3)
B4NI61_DROWI
180
2
19266
TrEMBL
other Location (Reliability: 2)
B3MRB0_DROAN
199
0
22219
TrEMBL
other Location (Reliability: 4)
HSP77_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
654
0
70628
Swiss-Prot
other Location (Reliability: 1)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
18000
18000
-
x * 18000, mass spectrometry, required for import of proteins into mitochondria by presequence translocase-associated motor PAM, stimulates ATPase activity of PAM
18000
-
x * 18000, subunit of presequence translocase-associated motor PAM, stimulates ATPase activity of PAM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
?
-
x * 18000, mass spectrometry, required for import of proteins into mitochondria by presequence translocase-associated motor PAM, stimulates ATPase activity of PAM
?
-
x * 18000, subunit of presequence translocase-associated motor PAM, stimulates ATPase activity of PAM
additional information
-
DnaK comprises two main domains: a 44-kDa N-terminal nucleotide-binding domain that contains ATPase activity, and a 25-kDa substrate-binding domain that harbors the substrate-binding site. NMR structure determination and analysis of wild-type,full-length DnaK, complexed with the peptide NRLLLTG and with ADP, using NMR residual dipolar coupling and spin labeling methods in aqueous solution based on available crystal structures of the domains, overview
additional information
-
in absence of nucleotides, Hsp70 also forms oligomeric aggregates of high molecular weight
additional information
-
subunit TIM44 forms a complex with the matrix-heat-shock protein Hsp70
additional information
-
Tim23/17 cooperates with the peripheral membrane protein Tim44, and the matrix heat shock protein mtHsp70 in preprotein import
additional information
-
MIM23, MIM17, MIM33 and MIM14 are constituents of the preprotein import machinery of the inner mitochondria membrane. The MIM complex constitutes a proteinaceous channel that accepts preprotein from the mitochonrial outer membrane complex, MOM, facilitates their reversible transmembrane movement, and mediates unidirectional transport by linkage to the ATP-dependent mtHsp70-MIM44 stystem
additional information
-
the TIM protein complex contains three essential Tim proteins. Tim17 and Tim23 are thought to build a preprotein translocation channel, while Tim44 transiently interacts with the matrix heat shock protein Hsp70 to form an ATP-driven import motor, there also consists a functional interaction between the matrix heat shock protein Hsp70 with Tim17
additional information
-
MIM44 with a MW of 44000 Da is a component of the mitochondrial inner membrane import machinery and interacts with preproteins in an early step of translocation
additional information
-
peripheral membrane protein Tim44 interacts both with the ATPase and peptide-binding domains of enzyme, model for efficient translocation across the mitochondrial inner membrane through regulated interactions
additional information
-
protein Pam16 forms a complex with Pam18 and specifically inhibits the Pam18-mediated stimulation of the ATPase activity of mtHsp70. Pam16 is a new type of cochaperone, part of the presequence translocase-associated motor PAM, and regulates the interaction of mtHsp70 with precursor proteins during import into mitochondria
additional information
the ATPase and peptide binding domain (PBD) of Hsp70 proteins are connected by a linker segment that mediates communication between the domains. The minimal co-chaperone Hep1 binding entity of Ssc1 consists of the ATPase domain and the interdomain linker. The ATPase domain in combination with the interdomain linker is crucial for aggregation of Ssc1, stimulating the ATPase activity. In the absence of Hep1, the ATPase domain with the interdomain linker aggregated
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
the enzyme is phosphorylated within the TPR domain at position S568. Phosphorylation of the enzyme has a negative regulatory effect on protein import
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in complex with the Hsp90, sitting drop vapor diffusion method, using 0.1 M citric acid, pH 3.5, 25% (w/v) PEG 3350
-
study of the structural interactions of Hsc70 ATPase domains with four different NEFs (nucleotide exchange factors) using PDB-ID: 1HPM. Two classes of key residues are distinguished in the domain: highly conserved residues involved in the nucleotide binding and not conserved but co-evolved and highly mobile residues, engaged in specific interactions with NEFs, i.e. N57, R258, R262, E283, And D285. Functional variability accompanied by structural variability at the co-chaperone binding sites and conservation/robustness both in terms of sequence and structural dynamics at the nucleotide binding sites are evolutionary optimized and is essential for adapting to interactions with differnent cofactors while meintaining ATPase activity
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Y196A/N198A/D199A
-
YND mutant, shows 3fold elevated basal activity in comparison with wild-type. The mutant also shows a significant decrease in Hsp70 escort protein Hep stimulation as in comparison to the wild-type protein. The YND mutant also exhibits a decreased stimulation of the J-protein splice variant hTid-1S in comparison of the wild-type further supporting the mutually exclusive nature of Hep and J-protein interaction at the ATPase domain of human mtHsp70
E240A/V241A
-
the mutation is supposed to affect both a cluster of charge interactions with Lys546 and Arg437 of the mtHsp70 substrate-binding domain, as well as hydrophobic interactions at the interface between the two Hsp70 domains, e.g. Ala542 within alpha-helix A of the substrate-binding domain. Lethal mutation due to a defect in allosteric regulation, phenotype, overview. No complementation of a ssc1 null mutant
N175A/D176A
-
the mutation abolishes a salt bridge that is formed between Asp176 of the nucleotide-binding domain and Lys544 of the substrate-binding domain. The mutant shows a temperature-sensitive phenotype with defect growth at 30°C due to a defect in allosteric regulation, phenotype, overview. No complementation of a ssc1 null mutant
Y173A
-
residue Tyr173, that is exposed on the molecular surface and located close to both the nucleotide-binding site and the putative domain interface. The mutant displays normal growth that is indistinguishable from cells expressing wild-type Ssc1. Complementation of a ssc1 null mutant
additional information
additional information
-
a T-DNA insertion line for cpHsc70-1 DELTAcpHsc70-1 has variegated cotyledons, malformed leaves, growth retardation, impaired root growth and sensitivity to heat shock treatment. In addition, under stress conditions, the mutant exhibits unusual sepals, and malformed flowers
additional information
-
construction of chimera of protein with yeast mtHsp70, alpha-helices A and B of the peptide binding domain of mtHsp70 are required to transmit the nucleotide state of the ATPase domain to the peptide domain in yeast mitochondria
additional information
-
recombinant GST-tagged mortalin/mtHsp70 deletion mutants, which demonstrate binding of mortalin via its N-terminal region
additional information
-
construction of fusion proteins consisting of a mitochondrial presequence containing the first mtHsp70 binding site, a spacer sequence containing an Hsp70 avoidance segment followed by the second mtHsp70 binding site, and different folded mature domains. Analysis of the dependence of the import rates of those fusion proteins on the lengths of Hsp70 avoidance segments, overview. Import of radiolabeled fusion proteins into isolated Saccharomyces cerevisiae mitochondria
additional information
-
construction of chimera of protein with yeast mtHsp70, alpha-helices A and B of the peptide binding domain of mtHsp70 are required to transmit the nucleotide state of the ATPase domain to the peptide domain. Tim44 is proposed to coordinate the binding of mtHsp70 to the incoming preprotein and the subsequent release of the mtHsp70-preprotein complex from the translocase of the inner membrane
additional information
-
generation of specific mtHsp70 mutations located within or close to the interface between the nucleotide-binding and the substrate-binding domains. Mitochondria isolated from mtHsp70 mutants display severely reduced import efficiencies in vitro. Two of the mutants exhibit strong growth defects in vivo and are significantly impaired in the generation of an inward-directed, ATP-dependent import force on precursor proteins in transit. Mutants show defects in the transfer of conformational signals to the substrate-binding domain, resulting in a prolonged and enhanced interaction with imported substrate proteins. Furthermore, interference with the allosteric mechanism results in defects of translocation-specific partner protein interaction
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
51.6
-
thermal denaturation of mtHsp70 shows three endotherms centered at 51.6, 67.5 and 76.2°C, the endotherm at 51.6°C may represent the unfolding of a more stable ATPase domain
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
mtHsp70 and Hsp70 ATPase domain remain soluble in the absence of Hep and nucleotides when stored in Tris at pH 8.0. In the case of the ATPase domain, the protein remains soluble at concentrations as high as 0.2 mM even when stored for 24 h at room temperature. However, the mtHsp70 ATPase domain could not be stably stored at high concentrations for a similar period of time in buffers having pH values more closely resembling the physiological environment within Escherichia coli where these proteins are overexpressed, unless it is incubated with equimolar Hep
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by ion exchange, ATP-agarose affinity and hydroxyapatite chromatographies
-
isolation of mitochondria from Saccharomyces cerevisiae cells recombinantly expressing His-tagged mtHsp70, and further purification by nickel affinity chromatography
-
purified on nickel-Sepharose, by ion exchange on a Mono Q column, and by gel filtration
recombinant C-terminally His-tagged enzyme from Triticum aestivum germ lysates by nickel affinity chromatography
-
recombinant His-tagged full-length enzyme and isolated ATPase domain from Escherichia coli by nickel affinity chromatography, ammonium sulfate fractionation, anion exchange chromatography, and gel filtration
-
purified on nickel-Sepharose, by ion exchange on a Mono Q column, and by gel filtration
-
purified on nickel-Sepharose, by ion exchange on a Mono Q column, and by gel filtration
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
chimeric Hsp70s overexpressed in BB1553 cells, mtHsp70 overexpressed in the yeast strain YKN3B
-
cloned in Escherichia coli, expression of ATPase and co-expression of the Hep1 in plasmids containing Ssc1 constructs
cpHsc70-1 and cpHsc70-2 cDNAs are PCR amplified and cloned into NdeI and XhoI sites of pET28a and introduced into Escherichia coli BL21(DE3)
-
expression of mtHsp70 and its isolated ATPase domain, as well as the ATPase fused to the peptide-binding domain of HscA, in Escherichia coli as insoluble proteins
-
for purification of the His-tagged human mtHsp70, coexpression is carried out with yeast Hsp70 escort protein Hep in Escherichia coli BL21(DE3)
-
HEK-293 cells are transiently transfected with pHep-EGFP, expression of C-terminally His-tagged Hsp70 without its N-terminal mitochondrial targeting sequence in Escherichia coli, the enzyme is insoluble in absence of human escort protein Hep, also as isolated ATPase domain and a chimera having this domain fused to the peptide-binding domain of HscA, a soluble monomeric chaperone
-
recombinant production of the C-terminally His-tagged enzyme by Triticum aestivum germ lysates, co-expression with the proteins of the interactome of the TIM23 core complex
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression patterns for cpHsc70-1 and cpHsc70-2 genes analyzed using the GUS (beta-gucuronidase) reporter gene. High Expression determined throughout seedlings, in all tissues of mature plants, unaltered in the drak or low light. Both genes are ubiquitously expressed at high levels, cpHsc70-1 slightly higher than cpHsc70-2, especially in roots
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
additional information
medicine
-
import of the enteropathogenic Escherichia coli effector protein Map into mitochondria, which alters organelle morphology, is dependent on mtHsp70
medicine
-
in vivo binding of mortalin/mtHsp70 with HSP60, involvment in tumorigenesis, functional distinction in pathways involved in senescence
medicine
-
mtHsp70 forms complexes with wild-type DJ-1 and its mutants, DJ-1 is an oncogene and causative gene for familial form of the Parkinson's disease, translocation of DJ-1 to mitochondria after oxidative stress is carried out in association with chaperones like mtHsp70
additional information
-
mtHsp70 and Escherichia coli DnaK display different conformational and biochemical properties, chimeric Hsp70s can not complement DnaK function in vivo
additional information
-
Pam16 is selectively required for preprotein translocation into the matrix, but not for protein insertion into the inner membrane, Pam16 interacts with Pam18 and is needed for the association of Pam18 with the presequence translocase and for formation of a mtHsp70-Tim44 complex
additional information
-
Pam16's J-like domain strongly interacts with Pam18's J domain, leading to a productive interaction of Pam18 with mtHsp70 at the import channel
additional information
-
Pam16-Pam18 complex regulates the ATpase activity of mtHsp70, Pam17 is required for the correct organization of the Pam16-Pam18 complex and thus contributes to regulation of mtHsp70 activity
additional information
-
Tam41 faciliates mitochondrial protein import by maintaining the functional integrity of the TIM23 protein translocator complex, TIM44 provides an anchor for mtHsp70 to bind to the translocating polypeptide that emerges from the outlet of the TIM23 channel
additional information
-
the TIM23 complex is not a static complex but switches between TOM tethering and PAM binding, including the subunit mtHsp70, in a reaction cycle involving Tim21 and Tim17
additional information
-
Tim15/Zim17 cooperates with mtHsp70 to faciliate import of presequence-containing proteins into the matrix
additional information
-
TIM44 binds to the peptide-binding domain of Hsp70 and thereby recruits it to the outlet of the translocation pore, so that mtHsp70 can bind to the incoming polypeptide chain as soon as it emerges from the channel
additional information
-
truncation of the N terminus of TIM17, a subunit of the TIM23 complex, severely diminishes mitochondrial import of preproteins, mitochondrial Hsp70 mediates the vectorial translocation of the preprotein into the matrix
additional information
-
truncation of the N terminus of TIM17, a subunit of the TIM23 complex, severely diminishes mitochondrial import of preproteins, mitochondrial Hsp70 mediates the vectorial translocation of the preprotein into the matrix
-
additional information
-
Tim15/Zim17 cooperates with mtHsp70 to faciliate import of presequence-containing proteins into the matrix
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Boemer, U.; Maarse, A.C.; Martin, F.; Geissler, A.; Merlin, A.; Schoenfisch, B.; Meijer, M.; Pfanner, N.; Rassow, J.
Separation of structural and dynamic functions of the mitochondrial translocase: Tim44 is crucial for the inner membrane import sites in translocation of tightly folded domains, but not of loosely folded preproteins
EMBO J.
17
4226-4237
1998
Saccharomyces cerevisiae
brenda
Boemer, U.; Meijer, M.; Maarse, A.C.; Hoenlinger, A.; Dekker, P.J.T.; Pfanner, N.; Rassow, J.
Multiple interactions of components mediating preprotein translocation across the inner mitochondrial membrane
EMBO J.
16
2205-2216
1997
Saccharomyces cerevisiae
brenda
Hwang, S.T.; Schatz, G.
Translocation of proteins across the mitochondrial inner membrane, but not into the outer membrane, required nucleoside triphosphates in the matrix
Proc. Natl. Acad. Sci. USA
86
8432-8436
1989
Saccharomyces cerevisiae
brenda
Blom, J.; Kuebrich, M.; Rassow, J.; Voos, W.; Dekker, P.J.T.; Maarse, A.C.; Meijer, M.; Pfanner, N.
The essential yeast protein MIM44 (encoded by MP1I1) is involved in an early step of preprotein translocation across the mitochondrial inner membrane
Mol. Cell. Biol.
13
7364-7371
1993
Saccharomyces cerevisiae
brenda
Voos, W.; Martin, H.; Krimmer, T.; Pfanner, N.
Mechanism of protein translocation into mitochondria
Biochim. Biophys. Acta
1422
235-254
1999
Saccharomyces cerevisiae
brenda
Berthold, J.; Bauer, M.F.; Schneider, H.C.; Klaus, C.; Dietmeier, K.; Neupert, W.; Brunner, M.
The MIM complex mediates preprotein translocation across the mitochondrial inner membrane and couples it to the mt-Hsp70/ATP driving system
Cell
81
1085-1093
1995
Saccharomyces cerevisiae
brenda
Moro, F.; Okamoto, K.; Donzeau, M.; Neupert, W.; Brunner, M.
Mitochondrial protein import: Molecular basis of the ATP-dependent interaction of MtHsp70 with Tim44
J. Biol. Chem.
277
6874-6880
2002
Saccharomyces cerevisiae, Escherichia coli
brenda
Li, Y.; Dudek, J.; Guiard, B.; Pfanner, N.; Rehling, P.; Voos, W.
The presequence translocase-associated protein import motor of mitochondria. Pam16 functions in an antagonistic manner to Pam18
J. Biol. Chem.
279
38047-38054
2004
Saccharomyces cerevisiae
brenda
Truscott, K.N.; Voos, W.; Frazier, A.E.; Lind, M.; Li, Y.; Geissler, A.; Dudek, J.; Muller, H.; Sickmann, A.; Meyer, H.E.; Meisinger, C.; Guiard, B.; Rehling, P.; Pfanner, N.
A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria
J. Cell Biol.
163
707-713
2003
Saccharomyces cerevisiae
brenda
D'Silva, P.; Liu, Q.; Walter, W.; Craig, E.A.
Regulated interactions of mtHsp70 with Tim44 at the translocon in the mitochondrial inner membrane
Nat. Struct. Mol. Biol.
11
1084-1091
2004
Saccharomyces cerevisiae
brenda
D'Silva, P.D.; Schilke, B.; Walter, W.; Andrew, A.; Craig, E.A.
J protein cochaperone of the mitochondrial inner membrane required for protein import into the mitochondrial matrix
Proc. Natl. Acad. Sci. USA
100
13839-13844
2003
Saccharomyces cerevisiae
brenda
Wadhwa, R.; Takano, S.; Kaur, K.; Aida, S.; Yaguchi, T.; Kaul, Z.; Hirano, T.; Taira, K.; Kaul, S.C.
Identification and characterization of molecular interactions between mortalin/mtHsp70 and HSP60
Biochem. J.
391
185-190
2005
Homo sapiens
brenda
Moro, F.; Fernandez-Saiz, V.; Slutsky, O.; Azem, A.; Muga, A.
Conformational properties of bacterial DnaK and yeast mitochondrial Hsp70. Role of the divergent C-terminal alpha-helical subdomain
FEBS J.
272
3184-3196
2005
Saccharomyces cerevisiae
brenda
Mokranjac, D.; Neupert, W.
Protein import into mitochondria
Biochem. Soc. Trans.
33
1019-1023
2005
Homo sapiens
brenda
Chacinska, A.; Lind, M.; Frazier, A.E.; Dudek, J.; Meisinger, C.; Geissler, A.; Sickmann, A.; Meyer, H.E.; Truscott, K.N.; Guiard, B.; Pfanner, N.; Rehling, P.
Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17
Cell
120
817-829
2005
Saccharomyces cerevisiae
brenda
Papatheodorou, P.; Doma?ska, G.; Oxle, M.; Mathieu, J.; Selchow, O.; Kenny, B.; Rassow, J.
The enteropathogenic Escherichia coli (EPEC) Map effector is imported into the mitochondrial matrix by the TOM/Hsp70 system and alters organelle morphology
Cell. Microbiol.
8
677-689
2006
Saccharomyces cerevisiae
brenda
Mokranjac, D.; Bourenkov, G.; Hell, K.; Neupert, W.; Groll, M.
Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor
EMBO J.
25
4675-4685
2006
Saccharomyces cerevisiae, Saccharomyces cerevisiae YPH499
brenda
Yamamoto, H.; Momose, T.; Yatsukawa, Y.; Ohshima, C.; Ishikawa, D.; Sato, T.; Tamura, Y.; Ohwa, Y.; Endo, T.
Identification of a novel member of yeast mitochondrial Hsp70-associated motor and chaperone proteins that facilitates protein translocation across the inner membrane
FEBS Lett.
579
507-511
2005
Saccharomyces cerevisiae, Saccharomyces cerevisiae PK81
brenda
Li, H.M.; Niki, T.; Taira, T.; Iguchi-Ariga, S.M.; Ariga, H.
Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress
Free Radic. Res.
39
1091-1099
2005
Mus musculus
brenda
Regoes, A.; Zourmpanou, D.; Leon-Avila, G.; van der Giezen, M.; Tovar, J.; Hehl, A.B.
Protein import, replication, and inheritance of a vestigial mitochondrion
J. Biol. Chem.
280
30557-30563
2005
Giardia intestinalis, Giardia intestinalis WB / CC 30957
brenda
Mokranjac, D.; Sichting, M.; Popov-Celeketi?, D.; Berg, A.; Hell, K.; Neupert, W.
The import motor of the yeast mitochondrial TIM23 preprotein translocase contains two different J proteins, Tim14 and Mdj2
J. Biol. Chem.
280
31608-31614
2005
Saccharomyces cerevisiae
brenda
Meier, S.; Neupert, W.; Herrmann, J.M.
Conserved N-terminal negative charges in the Tim17 subunit of the TIM23 translocase play a critical role in the import of preproteins into mitochondria
J. Biol. Chem.
280
7777-7785
2005
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4743
brenda
Tamura, Y.; Harada, Y.; Yamano, K.; Watanabe, K.; Ishikawa, D.; Ohshima, C.; Nishikawa, S.; Yamamoto, H.; Endo, T.
Identification of Tam41 maintaining integrity of the TIM23 protein translocator complex in mitochondria
J. Cell Biol.
174
631-637
2006
Saccharomyces cerevisiae
brenda
van der Laan, M.; Chacinska, A.; Lind, M.; Perschil, I.; Sickmann, A.; Meyer, H.E.; Guiard, B.; Meisinger, C.; Pfanner, N.; Rehling, P.
Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor
Mol. Cell. Biol.
25
7449-7458
2005
Saccharomyces cerevisiae
brenda
Frazier, A.E.; Dudek, J.; Guiard, B.; Voos, W.; Li, Y.; Lind, M.; Meisinger, C.; Geissler, A.; Sickmann, A.; Meyer, H.E.; Bilanchone, V.; Cumsky, M.G.; Truscott, K.N.; Pfanner, N.; Rehling, P.
Pam16 has an essential role in the mitochondrial protein import motor
Nat. Struct. Mol. Biol.
11
226-233
2004
Saccharomyces cerevisiae
brenda
DSilva, P.R.; Schilke, B.; Walter, W.; Craig, E.A.
Role of Pam16s degenerate J domain in protein import across the mitochondrial inner membrane
Proc. Natl. Acad. Sci. USA
102
12419-12424
2005
Saccharomyces cerevisiae
brenda
van der Laan, M.; Wiedemann, N.; Mick, D.U.; Guiard, B.; Rehling, P.; Pfanner, N.
A role for Tim21 in membrane-potential-dependent preprotein sorting in mitochondria
Curr. Biol.
16
2271-2276
2006
Saccharomyces cerevisiae
brenda
Sherman, E.L.; Taylor, R.D.; Go, N.E.; Nargang, F.E.
Effect of mutations in Tom40 on stability of the translocase of the outer mitochondrial membrane (TOM) complex, assembly of Tom40, and import of mitochondrial preproteins
J. Biol. Chem.
281
22554-22565
2006
Neurospora crassa
brenda
Mokranjac, D.; Berg, A.; Adam, A.; Neupert, W.; Hell, K.
Association of the Tim14.Tim16 subcomplex with the TIM23 translocase is crucial for function of the mitochondrial protein import motor
J. Biol. Chem.
282
18037-18045
2007
Saccharomyces cerevisiae
brenda
Bhangoo, M.K.; Tzankov, S.; Fan, A.C.; Dejgaard, K.; Thomas, D.Y.; Young, J.C.
Multiple 40-kDa heat-shock protein chaperones function in Tom70-dependent mitochondrial import
Mol. Biol. Cell
18
3414-3428
2007
Rattus norvegicus, Homo sapiens (P11142)
brenda
Iosefson, O.; Levy, R.; Marom, M.; Slutsky-Leiderman, O.; Azem, A.
The Pam18/Tim14-Pam16/Tim16 complex of the mitochondrial translocation motor: the formation of a stable complex from marginally stable proteins
Protein Sci.
16
316-322
2007
Saccharomyces cerevisiae
brenda
Zhai, P.; Stanworth, C.; Liu, S.; Silberg, J.J.
The human escort protein Hep binds to the ATPase domain of mitochondrial hsp70 and regulates ATP hydrolysis
J. Biol. Chem.
283
26098-26106
2008
Homo sapiens
brenda
Yamano, K.; Kuroyanagi-Hasegawa, M.; Esaki, M.; Yokota, M.; Endo, T.
Step-size analyses of the mitochondrial Hsp70 import motor reveal the Brownian ratchet in operation
J. Biol. Chem.
283
27325-27332
2008
Homo sapiens
brenda
Becker, D.; Krayl, M.; Strub, A.; Li, Y.; Mayer, M.P.; Voos, W.
Impaired interdomain communication in mitochondrial Hsp70 results in the loss of inward-directed translocation force
J. Biol. Chem.
284
2934-2946
2009
Saccharomyces cerevisiae
brenda
Schiller, D.; Cheng, Y.C.; Liu, Q.; Walter, W.; Craig, E.A.
Residues of Tim44 involved in both association with the translocon of the inner mitochondrial membrane and regulation of mitochondrial Hsp70 tethering
Mol. Cell. Biol.
28
4424-4433
2008
Saccharomyces cerevisiae
brenda
Bertelsen, E.B.; Chang, L.; Gestwicki, J.E.; Zuiderweg, E.R.
Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate
Proc. Natl. Acad. Sci. USA
106
8471-8476
2009
Escherichia coli
brenda
Hong, W.; Chen, L.; Liu, Y.; Gao, W.
ATP hydrolysis is essential for Bag-1M-mediated inhibition of the DNA binding by the glucocorticoid receptor
Biochem. Biophys. Res. Commun.
390
77-81
2009
Chlorocebus aethiops
brenda
Goswami, A.V.; Chittoor, B.; DSilva, P.
Understanding the functional interplay between mammalian mitochondrial Hsp70 chaperone machine components
J. Biol. Chem.
285
19472-19482
2010
Homo sapiens
brenda
Blamowska, M.; Sichting, M.; Mapa, K.; Mokranjac, D.; Neupert, W.; Hell, K.
ATPase domain and interdomain linker play a key role in aggregation of mitochondrial Hsp70 chaperone Ssc1
J. Biol. Chem.
285
4423-4431
2010
Saccharomyces cerevisiae (P0CS90)
brenda
Latijnhouwers, M.; Xu, X.M.; Moller, S.G.
Arabidopsis stromal 70-kDa heat shock proteins are essential for chloroplast development
Planta
232
567-578
2010
Arabidopsis thaliana
brenda
Liu, Y.; Gierasch, L.M.; Bahar, I.
Role of Hsp70 ATPase domain intrinsic dynamics and sequence evolution in enabling its functional interactions with NEFs
PLoS Comput. Biol.
6
e1000931
2010
Bos taurus
brenda
Mehnert, C.S.; Rampelt, H.; Gebert, M.; Oeljeklaus, S.; Schrempp, S.G.; Kochbeck, L.; Guiard, B.; Warscheid, B.; van der Laan, M.
The mitochondrial ADP/ATP carrier associates with the inner membrane presequence translocase in a stoichiometric manner
J. Biol. Chem.
289
27352-27362
2014
Saccharomyces cerevisiae
brenda
Schulz, C.; Rehling, P.
Remodelling of the active presequence translocase drives motor-dependent mitochondrial protein translocation
Nat. Commun.
5
4349
2014
Saccharomyces cerevisiae
brenda
Schendzielorz, A.B.; Schulz, C.; Lytovchenko, O.; Clancy, A.; Guiard, B.; Ieva, R.; van der Laan, M.; Rehling, P.
Two distinct membrane potential-dependent steps drive mitochondrial matrix protein translocation
J. Cell Biol.
216
83-92
2017
Saccharomyces cerevisiae
brenda
Nickel, C.; Horneff, R.; Heermann, R.; Neumann, B.; Jung, K.; Soll, J.; Schwenkert, S.
Phosphorylation of the outer membrane mitochondrial protein OM64 influences protein import into mitochondria
Mitochondrion
44
93-102
2019
Arabidopsis thaliana
brenda
Yanoma, T.; Ogata, K.; Yokobori, T.; Ide, M.; Mochiki, E.; Toyomasu, Y.; Yanai, M.; Kogure, N.; Kimura, A.; Suzuki, M.; Nakazawa, N.; Bai, T.; Oyama, T.; Asao, T.; Shirabe, K.; Kuwano, H.
Heat shock-induced HIKESHI protects cell viability via nuclear translocation of heat shock protein 70
Oncol. Rep.
38
1500-1506
2017
Homo sapiens
brenda
Select items on the left to see more content.
EXTERNAL LINKS (specific for EC-Number 7.4.2.3)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
