DNAJC19

UniProt ID: Q96DA6
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

DNAJC19 (TIM14/TIMM14; DnaJ homolog subfamily C member 19) is a J-domain co-chaperone of the mitochondrial inner membrane. It is a single-pass inner-membrane protein with a short intermembrane-space N-terminus, one transmembrane helix, and a matrix-facing J-domain. As the J-protein of the presequence translocase-associated import motor (PAM), it stimulates the ATPase activity of matrix mitochondrial HSP70 (mortalin/HSPA9) to drive ATP-dependent translocation of presequence-bearing precursor proteins from the TIM23 channel into the matrix. It forms a regulatory heterodimeric subcomplex with PAM16/Magmas (TIMM16), which restrains its HSP70-stimulating activity, and is tethered to the TIM23 translocase. DNAJC19 also associates with the prohibitin complex via PHB2 and has been implicated in cardiolipin remodeling. Biallelic loss-of-function variants cause dilated cardiomyopathy with ataxia (DCMA) syndrome / 3-methylglutaconic aciduria type 5.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001405 PAM complex, Tim23 associated import motor
IBA
GO_REF:0000033 		ACCEPT
Summary: DNAJC19 is the J-protein component of the presequence translocase-associated import motor (PAM), the matrix-side motor of the TIM23 complex. Well supported for the human protein by co-immunoprecipitation with translocon components.
Reason: The PAM complex is the defining functional context of DNAJC19; human DNAJC19 co-precipitates with Magmas, hTim44 and hTim23 as part of the human translocon, and the orthology-based IBA is corroborated by direct experimental evidence.
Supporting Evidence:
PMID:20053669
Pull down of Magmas along with other translocon components such as hTim44, hTim23, DnaJC19 provides direct evidence for the association of Magmas with the human translocon
GO:0001671 ATPase activator activity
IBA
GO_REF:0000033 		ACCEPT
Summary: As a J-domain protein, DNAJC19 stimulates the ATPase activity of mitochondrial HSP70 (mortalin), the core molecular function that powers presequence import. Directly demonstrated for the human protein.
Reason: Human DNAJC19 directly stimulates human Mortalin (mtHSP70) ATPase activity via its J-domain; this is the central molecular function of the gene and is experimentally supported, not merely inferred.
Supporting Evidence:
PMID:20053669
we have observed upto 70% reduction in ATPase stimulating activity of human Mortalin by Magmas:DnaJC19 complex
PMID:19564938
J-domain containing proteins, DnaJs, usually enhance the ATPase activity of Hsp70 chaperones
GO:0030150 protein import into mitochondrial matrix
IBA
GO_REF:0000033 		ACCEPT
Summary: DNAJC19 participates in ATP-dependent import of precursor proteins across the inner membrane into the matrix, as the J-protein driving the import motor. The core biological process for the gene.
Reason: The motor activity of the PAM complex that DNAJC19 enables drives matrix protein import; this BP is the direct outcome of its ATPase-activator function and is supported by orthology and human experimental work.
Supporting Evidence:
PMID:19564938
The latter role is played by the membrane-bound J-domain-containing protein named Tim14/Pam18
GO:0005743 mitochondrial inner membrane
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic annotation of inner-membrane localization, consistent with the experimentally supported single-pass inner-membrane topology of DNAJC19.
Reason: Correct compartment; agrees with UniProt subcellular location and the IDA inner-membrane annotation.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0098800 inner mitochondrial membrane protein complex
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: DNAJC19 is part of inner-membrane protein complexes (TIM23/PAM). This generic complex term is correct but less informative than the specific PAM/TIM23 complex annotations.
Reason: Correct but generic; the specific PAM complex and TIM23 translocase complex annotations capture the same information more precisely.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0099617 matrix side of mitochondrial inner membrane
IEA
GO_REF:0000107 		ACCEPT
Summary: The J-domain of DNAJC19 faces the matrix side of the inner membrane, consistent with its topology and its role stimulating matrix mtHSP70.
Reason: Accurate sub-membrane localization matching the protein's topology, where the catalytic J-domain projects into the matrix to engage mtHSP70.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
Matrix side
GO:1900208 regulation of cardiolipin metabolic process
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: DNAJC19 has been implicated in cardiolipin remodeling through its association with the prohibitin complex (via PHB2). By-similarity/inferred; relevant to the DCMA disease phenotype but secondary to the import-motor function.
Reason: The cardiolipin-remodeling role is supported only by similarity and the prohibitin interaction; it is disease-relevant but not the core, experimentally established molecular function of DNAJC19.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
forms a complex with prohibitins to regulate cardiolipin remodeling
GO:0005743 mitochondrial inner membrane
NAS
PMID:10339406
Genetic and structural characterization of the human mitocho... 		ACCEPT
Summary: Inner-membrane localization asserted from the structural/genetic characterization of the human inner-membrane translocase. Consistent with all other evidence.
Reason: Correct localization, redundant with the IEA and IDA inner-membrane annotations for the same compartment.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0005744 TIM23 mitochondrial import inner membrane translocase complex
NAS
PMID:10339406
Genetic and structural characterization of the human mitocho... 		ACCEPT
Summary: DNAJC19 is part of the TIM23 inner-membrane presequence translocase, tethered via its subcomplex with PAM16/Magmas. Supported by human translocon co-immunoprecipitation.
Reason: Human DNAJC19 co-precipitates with TIM23 translocon components (hTim23, hTim44, Magmas); membership in the TIM23 translocase complex is well established.
Supporting Evidence:
PMID:20053669
Pull down of Magmas along with other translocon components such as hTim44, hTim23, DnaJC19 provides direct evidence for the association of Magmas with the human translocon
GO:0006886 intracellular protein transport
NAS
PMID:10339406
Genetic and structural characterization of the human mitocho... 		KEEP AS NON CORE
Summary: Generic protein-transport process term. DNAJC19's specific role is import of precursors into the mitochondrial matrix, captured more precisely by GO:0030150.
Reason: Correct but a high-level parent of the specific 'protein import into mitochondrial matrix' process; non-core because a more precise term applies.
Supporting Evidence:
PMID:19564938
The latter role is played by the membrane-bound J-domain-containing protein named Tim14/Pam18
GO:0030150 protein import into mitochondrial matrix
NAS
PMID:16055927
Mutation of DNAJC19, a human homologue of yeast inner mitoch... 		ACCEPT
Summary: The same core import process as the IBA annotation, asserted in the DCMA disease report describing DNAJC19 as an inner-membrane import co-chaperone.
Reason: Matrix protein import is the core biological process of DNAJC19, consistent across orthology, biochemistry and the disease description.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		KEEP AS NON CORE
Summary: High-throughput proteomic detection of DNAJC19 in mitochondria. Correct but less specific than the inner-membrane annotations.
Reason: Accurate but generic organelle localization; the inner-membrane / matrix-side annotations are more informative.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0098800 inner mitochondrial membrane protein complex
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: By-similarity assertion of inner-membrane complex membership, duplicating the IEA annotation of the same term. Correct but generic.
Reason: Correct but generic complex term; more precise PAM/TIM23 complex annotations supersede it.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0099617 matrix side of mitochondrial inner membrane
ISS
GO_REF:0000024 		ACCEPT
Summary: By-similarity assertion of matrix-side localization, duplicating the IEA annotation. Matches the protein's topology.
Reason: Accurate sub-membrane localization consistent with the matrix-facing J-domain topology.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
Matrix side
GO:1900208 regulation of cardiolipin metabolic process
ISS
GO_REF:0000024 		KEEP AS NON CORE
Summary: By-similarity cardiolipin-remodeling annotation, duplicating the IEA version. Implicated through the prohibitin complex; disease-relevant but secondary.
Reason: Supported only by similarity and the prohibitin interaction; not the core experimentally established function.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
forms a complex with prohibitins to regulate cardiolipin remodeling
GO:0005515 protein binding
IPI
PMID:19564938
The mitochondrial protein translocation motor: structural co... 		KEEP AS NON CORE
Summary: IPI interaction with PAM16/Magmas (Q9Y3D7). DNAJC19 forms a heterodimeric J/J-like subcomplex with PAM16; the bare 'protein binding' term is uninformative, but the interaction is real and central to its regulation.
Reason: Per curation guidelines bare protein binding is uninformative and not elevated to core, but the documented DNAJC19-PAM16 interaction (the regulatory module of the import motor) is genuine; the IPI partner Q9Y3D7 is TIMM16/PAM16/Magmas.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
Interacts with TIMM16/PAM16
GO:0005515 protein binding
IPI
PMID:20053669
Role of Magmas in protein transport and human mitochondria b... 		KEEP AS NON CORE
Summary: IPI interaction with PAM16/Magmas (Q9Y3D7) demonstrated in human mitochondria by reciprocal co-immunoprecipitation. The bare term is uninformative but the interaction is genuine and functionally important.
Reason: Bare protein binding is uninformative; the underlying DNAJC19-Magmas subcomplex interaction is real (it regulates DNAJC19's ATPase-stimulating activity) and is retained as non-core.
Supporting Evidence:
PMID:20053669
we have observed upto 70% reduction in ATPase stimulating activity of human Mortalin by Magmas:DnaJC19 complex
GO:0005743 mitochondrial inner membrane
IDA
PMID:20053669
Role of Magmas in protein transport and human mitochondria b... 		ACCEPT
Summary: Direct experimental evidence localizing DNAJC19 to the mitochondrial inner membrane as part of the human translocon. The strongest localization annotation.
Reason: IDA-supported inner-membrane localization, fully consistent with the protein's single-pass inner-membrane topology and translocon membership.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0032991 protein-containing complex
IDA
PMID:19564938
The mitochondrial protein translocation motor: structural co... 		KEEP AS NON CORE
Summary: Generic complex-membership annotation reflecting the DNAJC19-PAM16 heterodimer. Correct but uninformative relative to the specific PAM/TIM23 complex terms.
Reason: Accurate but generic; subsumed by the specific PAM complex and TIM23 translocase annotations.
Supporting Evidence:
PMID:19564938
heterodimeric complexes and that these complexes interact with yeast mtHsp
GO:0032991 protein-containing complex
IDA
PMID:20053669
Role of Magmas in protein transport and human mitochondria b... 		KEEP AS NON CORE
Summary: Generic complex-membership annotation from the human translocon co-IP. Correct but uninformative relative to the specific complex terms.
Reason: Accurate but generic; the specific PAM/TIM23 complex annotations are more informative.
Supporting Evidence:
PMID:20053669
Pull down of Magmas along with other translocon components such as hTim44, hTim23, DnaJC19 provides direct evidence for the association of Magmas with the human translocon
GO:0005739 mitochondrion
IDA
PMID:12592411
Characterization of the human heart mitochondrial proteome. 		KEEP AS NON CORE
Summary: Direct detection of DNAJC19 in the human heart mitochondrial proteome. Correct but less specific than the inner-membrane annotations.
Reason: Accurate but generic organelle localization; the inner-membrane / matrix-side annotations are more precise.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane
GO:0016020 membrane
NAS
PMID:16055927
Mutation of DNAJC19, a human homologue of yeast inner mitoch... 		KEEP AS NON CORE
Summary: High-level membrane localization asserted in the DCMA disease report. Correct but very generic relative to the inner-membrane annotations.
Reason: Correct but a generic parent term; superseded by the specific inner-membrane localization.
Supporting Evidence:
file:human/DNAJC19/DNAJC19-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion inner membrane

Core Functions

J-domain co-chaperone that stimulates the ATPase activity of matrix mitochondrial HSP70 (mortalin/HSPA9), the molecular function that powers the presequence translocase-associated import motor (PAM).

Molecular Function:
ATPase activator activity
Cellular Locations:
mitochondrial inner membrane matrix side of mitochondrial inner membrane
Supporting Evidence:
  • PMID:20053669
    we have observed upto 70% reduction in ATPase stimulating activity of human Mortalin by Magmas:DnaJC19 complex
  • PMID:19564938
    J-domain containing proteins, DnaJs, usually enhance the ATPase activity of Hsp70 chaperones

As the J-protein of the TIM23-associated import motor, DNAJC19 drives ATP-dependent translocation of presequence-bearing precursor proteins from the inner membrane into the mitochondrial matrix.

Molecular Function:
ATPase activator activity
Directly Involved In:
protein import into mitochondrial matrix
In Complex:
PAM complex, Tim23 associated import motor
Supporting Evidence:
  • PMID:20053669
    Pull down of Magmas along with other translocon components such as hTim44, hTim23, DnaJC19 provides direct evidence for the association of Magmas with the human translocon

References

GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:10339406
Genetic and structural characterization of the human mitochondrial inner membrane translocase.
  • Characterized the human TIM23/TIM17/TIM44 inner-membrane translocase that drives presequence import in cooperation with mtHSP70.
PMID:12592411
Characterization of the human heart mitochondrial proteome.
  • Detected DNAJC19/TIM14 in the human heart mitochondrial proteome by mass spectrometry.
PMID:16055927
Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition.
  • Biallelic DNAJC19 variants cause dilated cardiomyopathy with ataxia (DCMA) / 3-methylglutaconic aciduria type 5, identifying DNAJC19 as a human inner-membrane import co-chaperone.
PMID:19564938
The mitochondrial protein translocation motor: structural conservation between the human and yeast Tim14/Pam18-Tim16/Pam16 co-chaperones.
  • J-domain proteins such as Tim14/Pam18 enhance the ATPase activity of Hsp70 chaperones to promote tight substrate binding during import; human Tim14/Pam18 and Tim16/Pam16 form heterodimeric complexes that interact with mtHSP70.
PMID:20053669
Role of Magmas in protein transport and human mitochondria biogenesis.
  • Human DNAJC19 stimulates Mortalin (mtHSP70) ATPase activity, which is inhibited by the Magmas:DnaJC19 complex; DNAJC19 co-precipitates with the human TIM23 translocon (hTim44, hTim23, Magmas).
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
file:human/DNAJC19/DNAJC19-uniprot.txt
UniProt entry Q96DA6 (TIM14_HUMAN), Mitochondrial import inner membrane translocase subunit TIM14
  • Mitochondrial co-chaperone of the PAM complex; single-pass inner-membrane protein with matrix-side J-domain; stimulates ATP-dependent import; interacts with PHB2 (prohibitin complex) and TIMM16/PAM16; cause of DCMA syndrome.

Suggested Questions for Experts

Q: Does DNAJC19's prohibitin/cardiolipin-remodeling role represent a function separable from its import-motor activity, and which one underlies the DCMA cardiomyopathy?

Q: How does the DNAJC19-PAM16 (Magmas) heterodimer dynamically regulate mtHSP70 ATPase stimulation during active import versus resting states?

Suggested Experiments

Experiment: Reconstitute the human import motor in vitro with purified DNAJC19, PAM16, mtHSP70 and GRPEL to measure DNAJC19-dependent ATPase stimulation and precursor translocation, including disease-variant proteins.

Experiment: Conditional DNAJC19 depletion in cardiomyocytes followed by mitochondrial import assays and cardiolipin profiling to dissect import-motor versus cardiolipin-remodeling contributions to the DCMA phenotype.

Experiment: Cryo-EM of the human TIM23-PAM holo-translocase to define how the DNAJC19 J-domain engages mtHSP70 at the matrix exit of the channel.

📚 Additional Documentation

Notes

(DNAJC19-notes.md)

DNAJC19 (TIM14 / TIMM14) research notes

Identity

  • UniProt Q96DA6, TIM14_HUMAN, "Mitochondrial import inner membrane translocase subunit TIM14"; DnaJ homolog subfamily C member 19. 116 aa.
  • HGNC:30528. Chromosome 3. Belongs to the TIM14 family.
  • Topology: short intermembrane-space N-terminus (2-3), single transmembrane helix (4-24), then matrix-side J-domain (62-116). So a single-pass inner-membrane protein with its catalytic J-domain projecting into the matrix.

Core function

  • J-domain co-chaperone of the mitochondrial presequence translocase-associated import motor (PAM), the matrix-side motor of the TIM23 complex.
  • Stimulates the ATPase activity of mitochondrial HSP70 (mortalin/HSPA9) to drive ATP-dependent import of presequence-bearing precursor proteins across the inner membrane into the matrix.
  • PMID:19564938
  • Human DNAJC19 directly stimulates human mtHSP70 (Mortalin) ATPase activity; this is antagonized by Magmas/PAM16 PMID:20053669.

Partner / complex

  • Forms a stable heterodimeric subcomplex with Magmas (PAM16/TIMM16) through their related J/J-like domains; this is the regulatory module of the import motor. Demonstrated in human mitochondria by reciprocal coIP.
  • PMID:20053669
  • PMID:20053669
  • Part of the human TIM23 translocon: co-IP with Tim17 pulls down hTim44, hTim23, DnaJC19, Magmas PMID:20053669.
  • Human Tim14/Pam18 (DNAJC19) and human Tim16/Pam16 form hetero-oligomers and bind yeast mtHsp70 PMID:19564938.
  • UniProt SUBUNIT: interacts with PHB2 (associates DNAJC19 with prohibitin complex) and with TIMM16/PAM16; may be component of PAM complex (mtHSP70, GRPEL1/2, TIMM44, TIMM16, TIMM14). (By similarity.)

Localization

  • Mitochondrion inner membrane, single-pass, matrix side [UniProt SUBCELLULAR LOCATION]. Confirmed in human heart mito proteome PMID:12592411 and human mito proteome PMID:34800366.

Second function (cardiolipin)

  • UniProt FUNCTION (by similarity): "forms a complex with prohibitins to regulate cardiolipin remodeling." Underlies the 3-methylglutaconic aciduria / DCMA phenotype (a cardiolipin/Barth-like syndrome). This is ISS/by-similarity, kept as non-core but plausible.

Disease

  • DCMA syndrome = dilated cardiomyopathy with ataxia = 3-methylglutaconic aciduria type 5 (MGCA5), autosomal recessive PMID:16055927. Also testicular dysgenesis (genitalia development), optic features. The IMP annotations to "genitalia development" and "visual perception" derive from the human disease phenotype description.

Annotation review reasoning

  • Core MF: GO:0001671 ATPase activator activity (stimulates mtHSP70) - ACCEPT, directly demonstrated for human protein.
  • Core BP: GO:0030150 protein import into mitochondrial matrix - ACCEPT.
  • Core CC: PAM complex (GO:0001405) and mitochondrial inner membrane / matrix side - ACCEPT.
  • TIM23 translocase complex (GO:0005744) part_of - ACCEPT, human translocon coIP.
  • Cardiolipin regulation (GO:1900208) ISS/IEA - KEEP_AS_NON_CORE (by similarity, disease-relevant but secondary).
  • protein binding GO:0005515 IPI with Q9Y3D7 (=PAM16/Magmas) - KEEP_AS_NON_CORE (real interaction, uninformative term; informative is the J-domain/ATPase module).
  • protein-containing complex GO:0032991 IDA - KEEP_AS_NON_CORE (generic, real but redundant with PAM/TIM23 complex).
  • mitochondrion GO:0005739 IDA/HTP - ACCEPT (less specific than inner membrane but correct).
  • membrane GO:0016020 NAS - KEEP_AS_NON_CORE (generic).
  • intracellular protein transport GO:0006886 NAS - KEEP_AS_NON_CORE (generic parent of import into matrix).
  • Note: genitalia development / visual perception IMP terms are in the DR/UniProt GO set but NOT in the GOA tsv stub, so not reviewed here.

Pn Notes

(DNAJC19-pn-notes.md)

DNAJC19 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q96DA6
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07b
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: DNAJC19 (TIM14/TIMM14; DnaJ homolog subfamily C member 19) is a J-domain co-chaperone of the mitochondrial inner membrane. It is a single-pass inner-membrane protein with a short intermembrane-space N-terminus, one transmembrane helix, and a matrix-facing J-domain. As the J-protein of the presequence translocase-associated import motor (PAM), it stimulates the ATPase activity of matrix mitochondrial HSP70 (mortalin/HSPA9) to drive ATP-dependent translocation of presequence-bearing precursor proteins from the TIM23 channel into the matrix. It forms a regulatory heterodimeric subcomplex with PAM16/Magmas (TIMM16), which restrains its HSP70-stimulating activity, and is tethered to the TIM23 translocase. DNAJC19 also associates with the prohibitin complex via PHB2 and has been implicated in cardiolipin remodeling. Biallelic loss-of-function variants cause dilated cardiomyopathy with ataxia (DCMA) syndrome / 3-methylglutaconic aciduria type 5.
  • Existing/core annotation action counts: ACCEPT: 10; KEEP_AS_NON_CORE: 12

PN Consistency Summary

  • Consistency: Strong agreement. Notes, review and PN node all describe the prototypical TIM23/PAM J-protein that stimulates matrix HSP70 (mortalin/HSPA9). Experimentally established for the human protein (PMID:20053669: ~70% ATPase stimulation in the Magmas:DnaJC19 complex; PMID:19564938). No contradictions. This is the best-supported member of the six (vs DNAJC15's PAM18-orthologue role; correctly distinguished as the genuine TIM23-associated import J-protein).
  • PN story / NEW pressure: PN proposes GO:0030544 Hsp70 protein binding (verified real). The binding is genuine (DNAJC19 directly engages/stimulates mortalin), but the review already records the stronger, more informative GO:0001671 ATPase activator activity (experimentally supported). GO:0030544 is NOT a parent of GO:0001671 — it is the binding axis, broader/less informative than the existing activator-activity annotation. Not an ADD; the function is already captured better.
  • Evidence alignment: Excellent overlap on the import-motor biology. Review anchors on PMID:20053669 and PMID:19564938 (both VERIFIED) plus the DCMA disease paper PMID:16055927 (UNVERIFIED, uncached). PN reference titles align with the J-domain/Hsp70-stimulation framing.
  • Verdict: Consistent and well-supported; PN's Hsp70-binding projection is true but already captured more informatively (ATPase activator activity). No edits required.

Full Consistency Review

  • UniProt: Q96DA6 (TIM14/TIMM14) · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: Mitochondrial proteostasis | Chaperone | HSP70 system | J-domain containing HSP70 cochaperone (branch MI) ; PN-node mapping: type=mapped, scope=ok_for_propagation_to_go, GO:0030544 Hsp70 protein binding (goa_status=more_specific_than_existing_goa)
  • Consistency: Strong agreement. Notes, review and PN node all describe the prototypical TIM23/PAM J-protein that stimulates matrix HSP70 (mortalin/HSPA9). Experimentally established for the human protein (PMID:20053669: ~70% ATPase stimulation in the Magmas:DnaJC19 complex; PMID:19564938). No contradictions. This is the best-supported member of the six (vs DNAJC15's PAM18-orthologue role; correctly distinguished as the genuine TIM23-associated import J-protein).
  • PN story / NEW pressure: PN proposes GO:0030544 Hsp70 protein binding (verified real). The binding is genuine (DNAJC19 directly engages/stimulates mortalin), but the review already records the stronger, more informative GO:0001671 ATPase activator activity (experimentally supported). GO:0030544 is NOT a parent of GO:0001671 — it is the binding axis, broader/less informative than the existing activator-activity annotation. Not an ADD; the function is already captured better.
  • Mapping strategy: No node change warranted. As with DNAJC15, "more_specific_than_existing_goa" is inaccurate — GO:0030544 is not more specific than the existing GO:0001671 ATPase activator activity. The secondary cardiolipin/prohibitin role (ISS, GO:1900208) sits outside this node and is correctly non-core in the review.
  • Evidence alignment: Excellent overlap on the import-motor biology. Review anchors on PMID:20053669 and PMID:19564938 (both VERIFIED) plus the DCMA disease paper PMID:16055927 (UNVERIFIED, uncached). PN reference titles align with the J-domain/Hsp70-stimulation framing.
  • Verdict: Consistent and well-supported; PN's Hsp70-binding projection is true but already captured more informatively (ATPase activator activity). No edits required.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJC19/DNAJC19-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Mitochondrial proteostasis | Chaperone | HSP70 system | J-domain containing HSP70 cochaperone

  • UniProt: Q96DA6
  • In branches: MI
  • PN-node mapping records (path + ancestors):
    • [type] Mitochondrial proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0030544 Hsp70 protein binding]
      rationale: In the PN hierarchy, this type denotes J-domain cochaperones assigned to the HSP70 system. Their shared mechanistic role is direct interaction with HSP70-family chaperones, making Hsp70 protein binding the most defensible GO target in the current cache.
    • [group] Mitochondrial proteostasis|Chaperone|HSP70 system
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a specific GO class. The member genes span multiple activities, complexes, or contexts, so propagation from this node would overstate the shared biology; use narrower child or gene-level curations.
    • [class] Mitochondrial proteostasis|Chaperone
      status=no_mapping scope= GO=[]
      rationale: This PN class is too heterogeneous for a single safe GO mapping. In the workbook it mixes HSP70, HSP60, and HSP90 systems, small intermembrane-space chaperones, membrane-protein chaperones, and other mitochondrial-specific factors.
    • [branch] Mitochondrial proteostasis
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (1)

  • GO:0030544 Hsp70 protein binding | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Mitochondrial proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: Q96DA6
gene_symbol: DNAJC19
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DNAJC19 (TIM14/TIMM14; DnaJ homolog subfamily C member 19) is a J-domain co-chaperone of the mitochondrial inner membrane. It is a single-pass inner-membrane protein with a short intermembrane-space N-terminus, one transmembrane helix, and a matrix-facing J-domain. As the J-protein of the presequence translocase-associated import motor (PAM), it stimulates the ATPase activity of matrix mitochondrial HSP70 (mortalin/HSPA9) to drive ATP-dependent translocation of presequence-bearing precursor proteins from the TIM23 channel into the matrix. It forms a regulatory heterodimeric subcomplex with PAM16/Magmas (TIMM16), which restrains its HSP70-stimulating activity, and is tethered to the TIM23 translocase. DNAJC19 also associates with the prohibitin complex via PHB2 and has been implicated in cardiolipin remodeling. Biallelic loss-of-function variants cause dilated cardiomyopathy with ataxia (DCMA) syndrome / 3-methylglutaconic aciduria type 5.
alternative_products:
- name: '1'
  id: Q96DA6-1
- name: '2'
  id: Q96DA6-2
  sequence_note: VSP_047119
existing_annotations:
- term:
    id: GO:0001405
    label: PAM complex, Tim23 associated import motor
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: DNAJC19 is the J-protein component of the presequence translocase-associated import motor (PAM), the matrix-side motor of the TIM23 complex. Well supported for the human protein by co-immunoprecipitation with translocon components.
    action: ACCEPT
    reason: The PAM complex is the defining functional context of DNAJC19; human DNAJC19 co-precipitates with Magmas, hTim44 and hTim23 as part of the human translocon, and the orthology-based IBA is corroborated by direct experimental evidence.
    supported_by:
    - reference_id: PMID:20053669
      supporting_text: Pull down of Magmas along with other translocon components such as hTim44, hTim23, DnaJC19 provides direct evidence for the association of Magmas with the human translocon
- term:
    id: GO:0001671
    label: ATPase activator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: As a J-domain protein, DNAJC19 stimulates the ATPase activity of mitochondrial HSP70 (mortalin), the core molecular function that powers presequence import. Directly demonstrated for the human protein.
    action: ACCEPT
    reason: Human DNAJC19 directly stimulates human Mortalin (mtHSP70) ATPase activity via its J-domain; this is the central molecular function of the gene and is experimentally supported, not merely inferred.
    supported_by:
    - reference_id: PMID:20053669
      supporting_text: we have observed upto 70% reduction in ATPase stimulating activity of human Mortalin by Magmas:DnaJC19 complex
    - reference_id: PMID:19564938
      supporting_text: 'J-domain containing proteins, DnaJs, usually enhance the ATPase activity of Hsp70 chaperones'
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: DNAJC19 participates in ATP-dependent import of precursor proteins across the inner membrane into the matrix, as the J-protein driving the import motor. The core biological process for the gene.
    action: ACCEPT
    reason: The motor activity of the PAM complex that DNAJC19 enables drives matrix protein import; this BP is the direct outcome of its ATPase-activator function and is supported by orthology and human experimental work.
    supported_by:
    - reference_id: PMID:19564938
      supporting_text: 'The latter role is played by the membrane-bound J-domain-containing protein named Tim14/Pam18'
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic annotation of inner-membrane localization, consistent with the experimentally supported single-pass inner-membrane topology of DNAJC19.
    action: ACCEPT
    reason: Correct compartment; agrees with UniProt subcellular location and the IDA inner-membrane annotation.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion inner membrane'
- term:
    id: GO:0098800
    label: inner mitochondrial membrane protein complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: part_of
  review:
    summary: DNAJC19 is part of inner-membrane protein complexes (TIM23/PAM). This generic complex term is correct but less informative than the specific PAM/TIM23 complex annotations.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific PAM complex and TIM23 translocase complex annotations capture the same information more precisely.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion inner membrane'
- term:
    id: GO:0099617
    label: matrix side of mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: The J-domain of DNAJC19 faces the matrix side of the inner membrane, consistent with its topology and its role stimulating matrix mtHSP70.
    action: ACCEPT
    reason: Accurate sub-membrane localization matching the protein's topology, where the catalytic J-domain projects into the matrix to engage mtHSP70.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:1900208
    label: regulation of cardiolipin metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: DNAJC19 has been implicated in cardiolipin remodeling through its association with the prohibitin complex (via PHB2). By-similarity/inferred; relevant to the DCMA disease phenotype but secondary to the import-motor function.
    action: KEEP_AS_NON_CORE
    reason: The cardiolipin-remodeling role is supported only by similarity and the prohibitin interaction; it is disease-relevant but not the core, experimentally established molecular function of DNAJC19.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: forms a complex with prohibitins to regulate cardiolipin remodeling
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: NAS
  original_reference_id: PMID:10339406
  qualifier: located_in
  review:
    summary: Inner-membrane localization asserted from the structural/genetic characterization of the human inner-membrane translocase. Consistent with all other evidence.
    action: ACCEPT
    reason: Correct localization, redundant with the IEA and IDA inner-membrane annotations for the same compartment.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion inner membrane'
- term:
    id: GO:0005744
    label: TIM23 mitochondrial import inner membrane translocase complex
  evidence_type: NAS
  original_reference_id: PMID:10339406
  qualifier: part_of
  review:
    summary: DNAJC19 is part of the TIM23 inner-membrane presequence translocase, tethered via its subcomplex with PAM16/Magmas. Supported by human translocon co-immunoprecipitation.
    action: ACCEPT
    reason: Human DNAJC19 co-precipitates with TIM23 translocon components (hTim23, hTim44, Magmas); membership in the TIM23 translocase complex is well established.
    supported_by:
    - reference_id: PMID:20053669
      supporting_text: Pull down of Magmas along with other translocon components such as hTim44, hTim23, DnaJC19 provides direct evidence for the association of Magmas with the human translocon
- term:
    id: GO:0006886
    label: intracellular protein transport
  evidence_type: NAS
  original_reference_id: PMID:10339406
  qualifier: involved_in
  review:
    summary: Generic protein-transport process term. DNAJC19's specific role is import of precursors into the mitochondrial matrix, captured more precisely by GO:0030150.
    action: KEEP_AS_NON_CORE
    reason: Correct but a high-level parent of the specific 'protein import into mitochondrial matrix' process; non-core because a more precise term applies.
    supported_by:
    - reference_id: PMID:19564938
      supporting_text: 'The latter role is played by the membrane-bound J-domain-containing protein named Tim14/Pam18'
- term:
    id: GO:0030150
    label: protein import into mitochondrial matrix
  evidence_type: NAS
  original_reference_id: PMID:16055927
  qualifier: involved_in
  review:
    summary: The same core import process as the IBA annotation, asserted in the DCMA disease report describing DNAJC19 as an inner-membrane import co-chaperone.
    action: ACCEPT
    reason: Matrix protein import is the core biological process of DNAJC19, consistent across orthology, biochemistry and the disease description.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput proteomic detection of DNAJC19 in mitochondria. Correct but less specific than the inner-membrane annotations.
    action: KEEP_AS_NON_CORE
    reason: Accurate but generic organelle localization; the inner-membrane / matrix-side annotations are more informative.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion inner membrane'
- term:
    id: GO:0098800
    label: inner mitochondrial membrane protein complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: part_of
  review:
    summary: By-similarity assertion of inner-membrane complex membership, duplicating the IEA annotation of the same term. Correct but generic.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic complex term; more precise PAM/TIM23 complex annotations supersede it.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion inner membrane'
- term:
    id: GO:0099617
    label: matrix side of mitochondrial inner membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: By-similarity assertion of matrix-side localization, duplicating the IEA annotation. Matches the protein's topology.
    action: ACCEPT
    reason: Accurate sub-membrane localization consistent with the matrix-facing J-domain topology.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: Matrix side
- term:
    id: GO:1900208
    label: regulation of cardiolipin metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: By-similarity cardiolipin-remodeling annotation, duplicating the IEA version. Implicated through the prohibitin complex; disease-relevant but secondary.
    action: KEEP_AS_NON_CORE
    reason: Supported only by similarity and the prohibitin interaction; not the core experimentally established function.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: forms a complex with prohibitins to regulate cardiolipin remodeling
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19564938
  qualifier: enables
  review:
    summary: IPI interaction with PAM16/Magmas (Q9Y3D7). DNAJC19 forms a heterodimeric J/J-like subcomplex with PAM16; the bare 'protein binding' term is uninformative, but the interaction is real and central to its regulation.
    action: KEEP_AS_NON_CORE
    reason: Per curation guidelines bare protein binding is uninformative and not elevated to core, but the documented DNAJC19-PAM16 interaction (the regulatory module of the import motor) is genuine; the IPI partner Q9Y3D7 is TIMM16/PAM16/Magmas.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: Interacts with TIMM16/PAM16
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20053669
  qualifier: enables
  review:
    summary: IPI interaction with PAM16/Magmas (Q9Y3D7) demonstrated in human mitochondria by reciprocal co-immunoprecipitation. The bare term is uninformative but the interaction is genuine and functionally important.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding is uninformative; the underlying DNAJC19-Magmas subcomplex interaction is real (it regulates DNAJC19's ATPase-stimulating activity) and is retained as non-core.
    supported_by:
    - reference_id: PMID:20053669
      supporting_text: we have observed upto 70% reduction in ATPase stimulating activity of human Mortalin by Magmas:DnaJC19 complex
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IDA
  original_reference_id: PMID:20053669
  qualifier: located_in
  review:
    summary: Direct experimental evidence localizing DNAJC19 to the mitochondrial inner membrane as part of the human translocon. The strongest localization annotation.
    action: ACCEPT
    reason: IDA-supported inner-membrane localization, fully consistent with the protein's single-pass inner-membrane topology and translocon membership.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion inner membrane'
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:19564938
  qualifier: part_of
  review:
    summary: Generic complex-membership annotation reflecting the DNAJC19-PAM16 heterodimer. Correct but uninformative relative to the specific PAM/TIM23 complex terms.
    action: KEEP_AS_NON_CORE
    reason: Accurate but generic; subsumed by the specific PAM complex and TIM23 translocase annotations.
    supported_by:
    - reference_id: PMID:19564938
      supporting_text: heterodimeric complexes and that these complexes interact with yeast mtHsp
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IDA
  original_reference_id: PMID:20053669
  qualifier: part_of
  review:
    summary: Generic complex-membership annotation from the human translocon co-IP. Correct but uninformative relative to the specific complex terms.
    action: KEEP_AS_NON_CORE
    reason: Accurate but generic; the specific PAM/TIM23 complex annotations are more informative.
    supported_by:
    - reference_id: PMID:20053669
      supporting_text: Pull down of Magmas along with other translocon components such as hTim44, hTim23, DnaJC19 provides direct evidence for the association of Magmas with the human translocon
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:12592411
  qualifier: located_in
  review:
    summary: Direct detection of DNAJC19 in the human heart mitochondrial proteome. Correct but less specific than the inner-membrane annotations.
    action: KEEP_AS_NON_CORE
    reason: Accurate but generic organelle localization; the inner-membrane / matrix-side annotations are more precise.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion inner membrane'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: NAS
  original_reference_id: PMID:16055927
  qualifier: located_in
  review:
    summary: High-level membrane localization asserted in the DCMA disease report. Correct but very generic relative to the inner-membrane annotations.
    action: KEEP_AS_NON_CORE
    reason: Correct but a generic parent term; superseded by the specific inner-membrane localization.
    supported_by:
    - reference_id: file:human/DNAJC19/DNAJC19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion inner membrane'
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10339406
  title: Genetic and structural characterization of the human mitochondrial inner membrane translocase.
  findings:
  - statement: Characterized the human TIM23/TIM17/TIM44 inner-membrane translocase that drives presequence import in cooperation with mtHSP70.
    reference_section_type: RESULTS
- id: PMID:12592411
  title: Characterization of the human heart mitochondrial proteome.
  findings:
  - statement: Detected DNAJC19/TIM14 in the human heart mitochondrial proteome by mass spectrometry.
    reference_section_type: RESULTS
- id: PMID:16055927
  title: Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition.
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: "Publication not cached in publications/; the title (the original DCMA-syndrome gene-discovery paper linking DNAJC19 to disease) is plausible and directly relevant to the gene's biology, but cannot be confirmed against a checkable source here, so left UNVERIFIED rather than asserting VERIFIED from the title alone."
  findings:
  - statement: Biallelic DNAJC19 variants cause dilated cardiomyopathy with ataxia (DCMA) / 3-methylglutaconic aciduria type 5, identifying DNAJC19 as a human inner-membrane import co-chaperone.
    reference_section_type: RESULTS
- id: PMID:19564938
  title: 'The mitochondrial protein translocation motor: structural conservation between the human and yeast Tim14/Pam18-Tim16/Pam16 co-chaperones.'
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication title matches the YAML title; the text explicitly describes the J-domain protein human Tim14/Pam18 (DNAJC19) enhancing mtHsp70 ATPase activity and forming heterodimers with Tim16/Pam16, supporting the ATPase-activator core MF. Cited in core_functions.supported_by."
  findings:
  - statement: J-domain proteins such as Tim14/Pam18 enhance the ATPase activity of Hsp70 chaperones to promote tight substrate binding during import; human Tim14/Pam18 and Tim16/Pam16 form heterodimeric complexes that interact with mtHSP70.
    reference_section_type: RESULTS
- id: PMID:20053669
  title: Role of Magmas in protein transport and human mitochondria biogenesis.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publication title matches the YAML title; Results show human DNAJC19 stimulates Mortalin (mtHSP70) ATPase activity (reduced ~70% by the Magmas:DnaJC19 complex) and co-precipitates with the human TIM23 translocon, directly supporting both the ATPase-activator MF and the matrix-import process. Cited in core_functions.supported_by."
  findings:
  - statement: Human DNAJC19 stimulates Mortalin (mtHSP70) ATPase activity, which is inhibited by the Magmas:DnaJC19 complex; DNAJC19 co-precipitates with the human TIM23 translocon (hTim44, hTim23, Magmas).
    reference_section_type: RESULTS
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
  findings: []
- id: file:human/DNAJC19/DNAJC19-uniprot.txt
  title: UniProt entry Q96DA6 (TIM14_HUMAN), Mitochondrial import inner membrane translocase subunit TIM14
  findings:
  - statement: Mitochondrial co-chaperone of the PAM complex; single-pass inner-membrane protein with matrix-side J-domain; stimulates ATP-dependent import; interacts with PHB2 (prohibitin complex) and TIMM16/PAM16; cause of DCMA syndrome.
    reference_section_type: OTHER
core_functions:
- description: J-domain co-chaperone that stimulates the ATPase activity of matrix mitochondrial HSP70 (mortalin/HSPA9), the molecular function that powers the presequence translocase-associated import motor (PAM).
  molecular_function:
    id: GO:0001671
    label: ATPase activator activity
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  - id: GO:0099617
    label: matrix side of mitochondrial inner membrane
  supported_by:
  - reference_id: PMID:20053669
    supporting_text: we have observed upto 70% reduction in ATPase stimulating activity of human Mortalin by Magmas:DnaJC19 complex
  - reference_id: PMID:19564938
    supporting_text: 'J-domain containing proteins, DnaJs, usually enhance the ATPase activity of Hsp70 chaperones'
- description: As the J-protein of the TIM23-associated import motor, DNAJC19 drives ATP-dependent translocation of presequence-bearing precursor proteins from the inner membrane into the mitochondrial matrix.
  molecular_function:
    id: GO:0001671
    label: ATPase activator activity
  in_complex:
    id: GO:0001405
    label: PAM complex, Tim23 associated import motor
  supported_by:
  - reference_id: PMID:20053669
    supporting_text: Pull down of Magmas along with other translocon components such as hTim44, hTim23, DnaJC19 provides direct evidence for the association of Magmas with the human translocon
  directly_involved_in:
  - id: GO:0030150
    label: protein import into mitochondrial matrix
proposed_new_terms: []
suggested_questions:
- question: Does DNAJC19's prohibitin/cardiolipin-remodeling role represent a function separable from its import-motor activity, and which one underlies the DCMA cardiomyopathy?
- question: How does the DNAJC19-PAM16 (Magmas) heterodimer dynamically regulate mtHSP70 ATPase stimulation during active import versus resting states?
suggested_experiments:
- description: Reconstitute the human import motor in vitro with purified DNAJC19, PAM16, mtHSP70 and GRPEL to measure DNAJC19-dependent ATPase stimulation and precursor translocation, including disease-variant proteins.
- description: Conditional DNAJC19 depletion in cardiomyocytes followed by mitochondrial import assays and cardiolipin profiling to dissect import-motor versus cardiolipin-remodeling contributions to the DCMA phenotype.
- description: Cryo-EM of the human TIM23-PAM holo-translocase to define how the DNAJC19 J-domain engages mtHSP70 at the matrix exit of the channel.