DNAJC11

UniProt ID: Q9NVH1
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

DNAJC11 is a mitochondrial protein of the DnaJ/Hsp40 (DNAJC) family with an N-terminal J domain and a C-terminal family-specific beta-barrel/coiled-coil region. Its full-length isoform is a peripheral protein of the mitochondrial outer membrane, and it is a component of the mitochondrial intermembrane space bridging (MIB) complex that links the inner-membrane MICOS (mitochondrial contact site and cristae organizing system) complex with the outer-membrane SAM (sorting and assembly machinery) complex. Through these associations DNAJC11 is required for proper mitochondrial inner-membrane organization and the formation of cristae and cristae junctions. In mice, a hypomorphic splicing mutation in DnaJC11 causes motor neuron pathology with cristae disorganization, muscle weakness, lymphoid abnormalities and early lethality, establishing a link between DNAJC11 and neuromuscular disease.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0042407 cristae formation
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetically inferred role in cristae formation, consistent with DNAJC11's experimentally established function in mitochondrial inner-membrane/cristae organization via the MICOS/MIB complex.
Reason: Cristae formation is a core biological process for DNAJC11, supported by mouse loss-of-function (cristae disorganization) and its MICOS/MIB association.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
Required for mitochondrial inner membrane organization.
GO:0005739 mitochondrion
IEA
GO_REF:0000044 		ACCEPT
Summary: Automated transfer of mitochondrial localization, consistent with DNAJC11's established mitochondrial localization. The mitochondrial outer membrane is the more precise compartment.
Reason: Mitochondrial localization is experimentally established; this is a correct but general compartment annotation.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion
GO:0005741 mitochondrial outer membrane
IEA
GO_REF:0000044 		ACCEPT
Summary: Automated transfer of mitochondrial outer membrane localization, the precise compartment of the full-length DNAJC11 isoform.
Reason: The full-length isoform is a peripheral mitochondrial outer membrane protein, experimentally established (PMID:25111180).
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
[Isoform 1]: Mitochondrion outer membrane
GO:0005515 protein binding
IPI
PMID:17500595
Huntingtin interacting proteins are genetic modifiers of neu... 		KEEP AS NON CORE
Summary: High-throughput interaction (IntAct WITH huntingtin/HTT, P42858). The bare protein binding term records a real interaction but is uninformative.
Reason: Bare protein binding from a high-throughput screen; uninformative and not part of the core MICOS/cristae function.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:17500595 UniProtKB:P42858
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		KEEP AS NON CORE
Summary: High-throughput interactions (IntAct WITH PM20D2 Q8IYS1, VPS52 Q8N1B4, LXN Q9BS40). The bare protein binding term is uninformative.
Reason: Bare protein binding from a high-throughput screen with partners unrelated to DNAJC11's cristae/MICOS function; uninformative.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:Q8IYS1
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		KEEP AS NON CORE
Summary: BioPlex affinity-purification interactome capturing a DNAJC11-ARMC1 (Q9NVT9) interaction. Bare protein binding term.
Reason: Bare protein binding is uninformative; retained as a recorded interaction.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q9NVT9
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce... 		KEEP AS NON CORE
Summary: Interactome dataset capturing a DNAJC11-ARMC1 (Q9NVT9) interaction. Bare protein binding term.
Reason: Bare protein binding is uninformative; retained as a recorded interaction.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 UniProtKB:Q9NVT9
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func... 		KEEP AS NON CORE
Summary: Multimodal cell-maps interactome capturing a DNAJC11-ARMC1 (Q9NVT9) interaction. Bare protein binding term.
Reason: Bare protein binding is uninformative; retained as a recorded interaction.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q9NVT9
GO:0042407 cristae formation
IEA
GO_REF:0000120 		ACCEPT
Summary: Automated transfer of the cristae formation process, consistent with experimental and phylogenetic evidence for DNAJC11's role in cristae organization.
Reason: Cristae formation is a core biological process supported by loss-of-function and MICOS/MIB association.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
Required for mitochondrial inner membrane organization.
GO:0140275 MIB complex
IDA
PMID:25997101
QIL1 is a novel mitochondrial protein required for MICOS com... 		ACCEPT
Summary: DNAJC11 is a component of the mitochondrial intermembrane space bridging (MIB) complex linking MICOS and SAM, directly demonstrated.
Reason: Direct experimental evidence establishes DNAJC11 as part of the MIB complex, the structural basis of its cristae-organizing function.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.
GO:0005739 mitochondrion
IDA
GO_REF:0000052 		ACCEPT
Summary: HPA immunofluorescence showing mitochondrial localization, consistent with DNAJC11's established mitochondrial localization.
Reason: Mitochondrial localization is experimentally supported; correct but general relative to the outer-membrane annotation.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion
GO:0005741 mitochondrial outer membrane
EXP
PMID:25111180
A splicing mutation in the novel mitochondrial protein DNAJC... 		ACCEPT
Summary: Experimental evidence that the full-length 63 kDa DNAJC11 isoform localizes to the periphery of the mitochondrial outer membrane.
Reason: Direct experimental evidence establishes the mitochondrial outer membrane as the precise compartment of the principal DNAJC11 isoform.
Supporting Evidence:
PMID:25111180
The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		ACCEPT
Summary: High-throughput proteomics detection of mitochondrial localization, consistent with the established localization.
Reason: Mitochondrial localization is corroborated by direct experimental evidence; correct compartment.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion
GO:0007007 inner mitochondrial membrane organization
IC
PMID:26477565
Evolution and structural organization of the mitochondrial c... 		ACCEPT
Summary: Curator-inferred role (from MIB complex membership) in inner mitochondrial membrane organization, consistent with the cristae-organizing function of the MICOS/MIB system.
Reason: DNAJC11 is required for mitochondrial inner-membrane organization, supported by its MIB-complex membership and mouse loss-of-function phenotype.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
Required for mitochondrial inner membrane organization.
GO:0140275 MIB complex
HDA
PMID:26477565
Evolution and structural organization of the mitochondrial c... 		ACCEPT
Summary: High-throughput proteomics evidence that DNAJC11 is part of the MIB complex, consistent with the IDA annotation.
Reason: MIB-complex membership is corroborated by direct and high-throughput evidence; core to DNAJC11's function.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.
GO:0005739 mitochondrion
IDA
PMID:25997101
QIL1 is a novel mitochondrial protein required for MICOS com... 		ACCEPT
Summary: Direct experimental evidence for mitochondrial localization of DNAJC11.
Reason: Mitochondrial localization is experimentally established; correct compartment.
Supporting Evidence:
file:human/DNAJC11/DNAJC11-uniprot.txt
SUBCELLULAR LOCATION: Mitochondrion

Core Functions

Structural component of the mitochondrial intermembrane space bridging (MIB) complex that connects the inner-membrane MICOS complex to the outer-membrane SAM complex, organizing the mitochondrial inner membrane and cristae junctions.

Cellular Locations:
mitochondrial outer membrane
In Complex:
MIB complex
Supporting Evidence:
  • file:human/DNAJC11/DNAJC11-uniprot.txt
    The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.

Required for mitochondrial inner-membrane organization and cristae formation, acting via its MICOS/MIB associations; loss of function causes cristae disorganization.

Directly Involved In:
cristae formation
Cellular Locations:
mitochondrial outer membrane
Supporting Evidence:
  • file:human/DNAJC11/DNAJC11-uniprot.txt
    Required for mitochondrial inner membrane organization.
  • PMID:25111180
    motor neuron pathology associated with cristae disorganization

References

GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:17500595
Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
PMID:25111180
A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor neuron pathology associated with cristae disorganization, and lymphoid abnormalities in mice.
  • The full-length 63 kDa DNAJC11 isoform localizes to the periphery of the mitochondrial outer membrane and is assembled into a high-molecular-weight complex; mitofilin/SAM50 downregulation reduces DNAJC11 levels.
  • A hypomorphic DnaJC11 splicing mutation in mice causes motor neuron pathology with mitochondrial cristae disorganization and loss of proper inner-membrane organization.
PMID:25997101
QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology.
  • DNAJC11 associates with the MICOS complex and SAM complex as part of the mitochondrial intermembrane space bridging (MIB) complex regulating cristae junction structure.
PMID:26477565
Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex.
  • DNAJC11 is a component of the MICOS/MIB assembly that organizes the mitochondrial inner membrane and cristae.
PMID:32296183
A reference map of the human binary protein interactome.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
file:human/DNAJC11/DNAJC11-uniprot.txt
UniProt entry Q9NVH1 (DJC11_HUMAN), DnaJ homolog subfamily C member 11
  • Required for mitochondrial inner membrane organization; functions through association with the MICOS and SAM complexes as part of the MIB complex; full-length isoform is a peripheral mitochondrial outer membrane protein.

Suggested Questions for Experts

Q: Does the J domain of DNAJC11 recruit a mitochondrial HSP70 (e.g. HSPA9/mortalin) to the MIB complex, and is any co-chaperone activity required for cristae organization?

Q: What are the distinct functions of the differentially localized DNAJC11 isoforms (outer membrane vs inner-membrane/IMS forms)?

Suggested Experiments

Experiment: Reconstitute or immunopurify the MIB complex with wild-type versus J-domain-mutant DNAJC11 and assess MICOS/SAM assembly, cristae junction morphology (by electron microscopy), and recruitment of mitochondrial HSP70.

Experiment: Isoform-specific knockout/rescue in human cells followed by quantitative proteomics and cryo-EM tomography to define which DNAJC11 isoform supports cristae architecture and MICOS stability.

📚 Additional Documentation

Notes

(DNAJC11-notes.md)

DNAJC11 research notes

Identity

  • UniProt Q9NVH1 (DJC11_HUMAN), 559 aa. HGNC:25570. N-terminal J domain (14-82); C-terminal
    DNAJC11-specific beta-barrel + coiled-coil. Belongs to the DNAJC11 family.
  • Note: unlike canonical J proteins, DNAJC11's functional role is structural (cristae/MICOS) rather than
    a classic cytosolic HSP70 co-chaperone; no demonstrated HSP70 ATPase stimulation. HSPA9 (mortalin) is
    part of the larger MIB assembly but DNAJC11's MF is not well-defined as a co-chaperone.

Localization

  • Mitochondrion; isoform 1 (full-length, 63 kDa) is in the mitochondrial OUTER membrane (peripheral
    membrane protein); other isoforms differential submitochondrial.
    PMID:25111180
    [file:human/DNAJC11/DNAJC11-uniprot.txt "SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion outer membrane
    ...; Peripheral membrane protein"]

Function: MICOS/SAM/MIB & cristae

  • Required for mitochondrial inner membrane organization; functions through association with MICOS and
    the SAM complex. [file:human/DNAJC11/DNAJC11-uniprot.txt "Required for mitochondrial inner membrane
    organization. Seems to function through its association with the MICOS complex and the mitochondrial
    outer membrane sorting assembly machinery (SAM) complex."]
  • Part of the MIB (mitochondrial intermembrane space bridging) complex spanning both mito membranes.
    [uniprot SUBUNIT "The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex
    spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB)
    complex."]
  • Originally found in mitofilin (IMMT)/SAM50/metaxin complex. [PMID:17624330 - mitofilin complex with
    SAM50, metaxins 1/2, CHCHD3/6 and DnaJC11] (uniprot ref, not in GOA).
  • Mouse hypomorph: motor neuron pathology with cristae disorganization, mitochondria losing proper inner
    membrane organization. [PMID:25111180 "motor neuron pathology associated with cristae disorganization"
    ; "mitochondria that had lost their proper inner membrane organization"]
  • DNAJC11 assembled in a high MW complex; mitofilin/SAM50 downregulation affects DNAJC11 levels.
    PMID:25111180
  • MICOS subunit context [PMID:25997101 QIL1/MICOS]; DNAJC11 associates with the MICOS complex.

GOA WITH-partner key (bare protein binding rows)

  • P42858=HTT (huntingtin), Q8IYS1=PM20D2, Q8N1B4=VPS52, Q9BS40=LXN, Q9NVT9=ARMC1. These are mostly
    isolated high-throughput interactors not clearly tied to the MICOS/cristae function.

Review logic

CORE:
- MIB complex (GO:0140275, IDA part_of PMID:25997101): ACCEPT, CORE CC.
- cristae formation (GO:0042407, IBA/IEA): ACCEPT, CORE BP.
- inner mitochondrial membrane organization (GO:0007007, IC): ACCEPT, CORE BP.
- mitochondrial outer membrane (GO:0005741, EXP/IEA isoform 1): ACCEPT, CORE CC.
- mitochondrion (GO:0005739, IDA/IEA/HTP): ACCEPT (general, but mito OM is more precise).
Non-core / over-annotated:
- protein binding (GO:0005515, IPI x several HTT/PM20D2/VPS52/LXN/ARMC1): bare term KEEP_AS_NON_CORE.
- No classic HSP70 co-chaperone MF to assign; J domain present but cristae role is structural.

Pn Notes

(DNAJC11-pn-notes.md)

DNAJC11 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9NVH1
  • 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: DNAJC11 is a mitochondrial protein of the DnaJ/Hsp40 (DNAJC) family with an N-terminal J domain and a C-terminal family-specific beta-barrel/coiled-coil region. Its full-length isoform is a peripheral protein of the mitochondrial outer membrane, and it is a component of the mitochondrial intermembrane space bridging (MIB) complex that links the inner-membrane MICOS (mitochondrial contact site and cristae organizing system) complex with the outer-membrane SAM (sorting and assembly machinery) complex. Through these associations DNAJC11 is required for proper mitochondrial inner-membrane organization and the formation of cristae and cristae junctions. In mice, a hypomorphic splicing mutation in DnaJC11 causes motor neuron pathology with cristae disorganization, muscle weakness, lymphoid abnormalities and early lethality, establishing a link between DNAJC11 and neuromuscular disease.
  • Existing/core annotation action counts: ACCEPT: 11; KEEP_AS_NON_CORE: 5

PN Consistency Summary

  • Consistency: Contradiction. PN classifies DNAJC11 as a J-domain HSP70 co-chaperone and projects GO:0030544 Hsp70 binding. The review and notes explicitly state the opposite: DNAJC11's role is structural (MIB/MICOS/SAM, cristae organization); "no demonstrated HSP70 ATPase stimulation" and "DNAJC11's MF is not well-defined as a co-chaperone." The review deliberately assigns NO molecular-function/Hsp70-binding term and frames the gene around GO:0140275 (MIB complex), GO:0042407 (cristae formation), GO:0007007. GOA contains no GO:0030544 or even GO:0031072.
  • PN story / NEW pressure: PN asserts an HSP70-cochaperone role that is NOT in GOA and NOT supported by literature. This is the classic over-broad J-domain holdase/cochaperone inference flagged in the task. There is no defensible NEW Hsp70-binding term here; the gene's verified biology (cristae/MIB) is already captured. The PN goa_status=more_specific_than_existing_goa is also factually wrong — GOA lacks the parent GO:0031072, so it could at best be new_to_goa, but the assertion itself is unsupported.
  • Evidence alignment: PN row carries no titles; review anchors on PMID:25111180, 25997101, 26477565 (all verified, MIB/cristae). None supports Hsp70 binding. Full divergence from the PN cochaperone framing.
  • Verdict: PN over-reaches — DNAJC11 is a structural MIB/cristae protein, not a demonstrated HSP70 cochaperone. Recommended edits: [MAP] remove/exempt DNAJC11 from GO:0030544 propagation under the "J-domain containing HSP70 cochaperone" type; its propagating terms are GO:0140275 / GO:0042407.

Full Consistency Review

  • UniProt: Q9NVH1 · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: Mitochondrial proteostasis|Chaperone|HSP70 system|J-domain containing HSP70 cochaperone ; PN-node mapping: type=mapped, scope=ok_for_propagation_to_go, GO:0030544 Hsp70 protein binding (group/class/branch = no_mapping)
  • Consistency: Contradiction. PN classifies DNAJC11 as a J-domain HSP70 co-chaperone and projects GO:0030544 Hsp70 binding. The review and notes explicitly state the opposite: DNAJC11's role is structural (MIB/MICOS/SAM, cristae organization); "no demonstrated HSP70 ATPase stimulation" and "DNAJC11's MF is not well-defined as a co-chaperone." The review deliberately assigns NO molecular-function/Hsp70-binding term and frames the gene around GO:0140275 (MIB complex), GO:0042407 (cristae formation), GO:0007007. GOA contains no GO:0030544 or even GO:0031072.
  • PN story / NEW pressure: PN asserts an HSP70-cochaperone role that is NOT in GOA and NOT supported by literature. This is the classic over-broad J-domain holdase/cochaperone inference flagged in the task. There is no defensible NEW Hsp70-binding term here; the gene's verified biology (cristae/MIB) is already captured. The PN goa_status=more_specific_than_existing_goa is also factually wrong — GOA lacks the parent GO:0031072, so it could at best be new_to_goa, but the assertion itself is unsupported.
  • Mapping strategy: DNAJC11 should be treated as an exception to the J-domain-cochaperone type mapping (like the structural/non-canonical cases). Propagating GO:0030544 to DNAJC11 would assert an undemonstrated function. The node mapping is fine for genuine cochaperones but mis-includes DNAJC11.
  • Evidence alignment: PN row carries no titles; review anchors on PMID:25111180, 25997101, 26477565 (all verified, MIB/cristae). None supports Hsp70 binding. Full divergence from the PN cochaperone framing.
  • Verdict: PN over-reaches — DNAJC11 is a structural MIB/cristae protein, not a demonstrated HSP70 cochaperone. Recommended edits: [MAP] remove/exempt DNAJC11 from GO:0030544 propagation under the "J-domain containing HSP70 cochaperone" type; its propagating terms are GO:0140275 / GO:0042407.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/DNAJC11/DNAJC11-ai-review.yaml
  • PN workbook rows: 1

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

  • UniProt: Q9NVH1
  • 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: Q9NVH1
gene_symbol: DNAJC11
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: DNAJC11 is a mitochondrial protein of the DnaJ/Hsp40 (DNAJC) family with an N-terminal J domain and a C-terminal family-specific beta-barrel/coiled-coil region. Its full-length isoform is a peripheral protein of the mitochondrial outer membrane, and it is a component of the mitochondrial intermembrane space bridging (MIB) complex that links the inner-membrane MICOS (mitochondrial contact site and cristae organizing system) complex with the outer-membrane SAM (sorting and assembly machinery) complex. Through these associations DNAJC11 is required for proper mitochondrial inner-membrane organization and the formation of cristae and cristae junctions. In mice, a hypomorphic splicing mutation in DnaJC11 causes motor neuron pathology with cristae disorganization, muscle weakness, lymphoid abnormalities and early lethality, establishing a link between DNAJC11 and neuromuscular disease.
alternative_products:
- name: '1'
  id: Q9NVH1-1
- name: '2'
  id: Q9NVH1-2
  sequence_note: VSP_019933
- name: '3'
  id: Q9NVH1-3
  sequence_note: VSP_019932
existing_annotations:
- term:
    id: GO:0042407
    label: cristae formation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetically inferred role in cristae formation, consistent with DNAJC11's experimentally established function in mitochondrial inner-membrane/cristae organization via the MICOS/MIB complex.
    action: ACCEPT
    reason: Cristae formation is a core biological process for DNAJC11, supported by mouse loss-of-function (cristae disorganization) and its MICOS/MIB association.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: Required for mitochondrial inner membrane organization.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated transfer of mitochondrial localization, consistent with DNAJC11's established mitochondrial localization. The mitochondrial outer membrane is the more precise compartment.
    action: ACCEPT
    reason: Mitochondrial localization is experimentally established; this is a correct but general compartment annotation.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion'
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated transfer of mitochondrial outer membrane localization, the precise compartment of the full-length DNAJC11 isoform.
    action: ACCEPT
    reason: The full-length isoform is a peripheral mitochondrial outer membrane protein, experimentally established (PMID:25111180).
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: '[Isoform 1]: Mitochondrion outer membrane'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17500595
  qualifier: enables
  review:
    summary: High-throughput interaction (IntAct WITH huntingtin/HTT, P42858). The bare protein binding term records a real interaction but is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding from a high-throughput screen; uninformative and not part of the core MICOS/cristae function.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:17500595 UniProtKB:P42858
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: High-throughput interactions (IntAct WITH PM20D2 Q8IYS1, VPS52 Q8N1B4, LXN Q9BS40). The bare protein binding term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding from a high-throughput screen with partners unrelated to DNAJC11's cristae/MICOS function; uninformative.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:Q8IYS1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-purification interactome capturing a DNAJC11-ARMC1 (Q9NVT9) interaction. Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding is uninformative; retained as a recorded interaction.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:Q9NVT9
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: Interactome dataset capturing a DNAJC11-ARMC1 (Q9NVT9) interaction. Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding is uninformative; retained as a recorded interaction.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 UniProtKB:Q9NVT9
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-maps interactome capturing a DNAJC11-ARMC1 (Q9NVT9) interaction. Bare protein binding term.
    action: KEEP_AS_NON_CORE
    reason: Bare protein binding is uninformative; retained as a recorded interaction.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:40205054 UniProtKB:Q9NVT9
- term:
    id: GO:0042407
    label: cristae formation
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Automated transfer of the cristae formation process, consistent with experimental and phylogenetic evidence for DNAJC11's role in cristae organization.
    action: ACCEPT
    reason: Cristae formation is a core biological process supported by loss-of-function and MICOS/MIB association.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: Required for mitochondrial inner membrane organization.
- term:
    id: GO:0140275
    label: MIB complex
  evidence_type: IDA
  original_reference_id: PMID:25997101
  qualifier: part_of
  review:
    summary: DNAJC11 is a component of the mitochondrial intermembrane space bridging (MIB) complex linking MICOS and SAM, directly demonstrated.
    action: ACCEPT
    reason: Direct experimental evidence establishes DNAJC11 as part of the MIB complex, the structural basis of its cristae-organizing function.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence showing mitochondrial localization, consistent with DNAJC11's established mitochondrial localization.
    action: ACCEPT
    reason: Mitochondrial localization is experimentally supported; correct but general relative to the outer-membrane annotation.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion'
- term:
    id: GO:0005741
    label: mitochondrial outer membrane
  evidence_type: EXP
  original_reference_id: PMID:25111180
  qualifier: located_in
  review:
    summary: Experimental evidence that the full-length 63 kDa DNAJC11 isoform localizes to the periphery of the mitochondrial outer membrane.
    action: ACCEPT
    reason: Direct experimental evidence establishes the mitochondrial outer membrane as the precise compartment of the principal DNAJC11 isoform.
    supported_by:
    - reference_id: PMID:25111180
      supporting_text: The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput proteomics detection of mitochondrial localization, consistent with the established localization.
    action: ACCEPT
    reason: Mitochondrial localization is corroborated by direct experimental evidence; correct compartment.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion'
- term:
    id: GO:0007007
    label: inner mitochondrial membrane organization
  evidence_type: IC
  original_reference_id: PMID:26477565
  qualifier: involved_in
  review:
    summary: Curator-inferred role (from MIB complex membership) in inner mitochondrial membrane organization, consistent with the cristae-organizing function of the MICOS/MIB system.
    action: ACCEPT
    reason: DNAJC11 is required for mitochondrial inner-membrane organization, supported by its MIB-complex membership and mouse loss-of-function phenotype.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: Required for mitochondrial inner membrane organization.
- term:
    id: GO:0140275
    label: MIB complex
  evidence_type: HDA
  original_reference_id: PMID:26477565
  qualifier: part_of
  review:
    summary: High-throughput proteomics evidence that DNAJC11 is part of the MIB complex, consistent with the IDA annotation.
    action: ACCEPT
    reason: MIB-complex membership is corroborated by direct and high-throughput evidence; core to DNAJC11's function.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:25997101
  qualifier: located_in
  review:
    summary: Direct experimental evidence for mitochondrial localization of DNAJC11.
    action: ACCEPT
    reason: Mitochondrial localization is experimentally established; correct compartment.
    supported_by:
    - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Mitochondrion'
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:17500595
  title: Huntingtin interacting proteins are genetic modifiers of neurodegeneration.
  findings: []
- id: PMID:25111180
  title: A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor neuron pathology associated with cristae disorganization, and lymphoid abnormalities in mice.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; body confirms DNAJC11 localizes to the mitochondrial outer membrane in a high-MW complex and that a hypomorphic mutation causes cristae disorganization. GOA anchors this PMID to GO:0005741 (mitochondrial outer membrane, EXP) - the core localization/function.
  findings:
  - statement: The full-length 63 kDa DNAJC11 isoform localizes to the periphery of the mitochondrial outer membrane and is assembled into a high-molecular-weight complex; mitofilin/SAM50 downregulation reduces DNAJC11 levels.
    reference_section_type: ABSTRACT
  - statement: A hypomorphic DnaJC11 splicing mutation in mice causes motor neuron pathology with mitochondrial cristae disorganization and loss of proper inner-membrane organization.
    reference_section_type: ABSTRACT
- id: PMID:25997101
  title: QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication title matches PubMed; body confirms DNAJC11 associates with the MICOS/SAM (MIB) complex. GOA anchors this PMID to GO:0140275 (MIB complex, IDA) and GO:0005739, supporting DNAJC11's MIB-complex membership.
  findings:
  - statement: DNAJC11 associates with the MICOS complex and SAM complex as part of the mitochondrial intermembrane space bridging (MIB) complex regulating cristae junction structure.
    reference_section_type: RESULTS
- id: PMID:26477565
  title: Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached publication confirms DNAJC11 as a MICOS/MIB component; GOA anchors this PMID to GO:0140275 (MIB complex, HDA). Title corrected to verbatim PubMed.
  findings:
  - statement: DNAJC11 is a component of the MICOS/MIB assembly that organizes the mitochondrial inner membrane and cristae.
    reference_section_type: RESULTS
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: file:human/DNAJC11/DNAJC11-uniprot.txt
  title: UniProt entry Q9NVH1 (DJC11_HUMAN), DnaJ homolog subfamily C member 11
  findings:
  - statement: Required for mitochondrial inner membrane organization; functions through association with the MICOS and SAM complexes as part of the MIB complex; full-length isoform is a peripheral mitochondrial outer membrane protein.
    reference_section_type: OTHER
core_functions:
- description: Structural component of the mitochondrial intermembrane space bridging (MIB) complex that connects the inner-membrane MICOS complex to the outer-membrane SAM complex, organizing the mitochondrial inner membrane and cristae junctions.
  locations:
  - id: GO:0005741
    label: mitochondrial outer membrane
  supported_by:
  - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
    supporting_text: The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.
  in_complex:
    id: GO:0140275
    label: MIB complex
- description: Required for mitochondrial inner-membrane organization and cristae formation, acting via its MICOS/MIB associations; loss of function causes cristae disorganization.
  locations:
  - id: GO:0005741
    label: mitochondrial outer membrane
  supported_by:
  - reference_id: file:human/DNAJC11/DNAJC11-uniprot.txt
    supporting_text: Required for mitochondrial inner membrane organization.
  - reference_id: PMID:25111180
    supporting_text: motor neuron pathology associated with cristae disorganization
  directly_involved_in:
  - id: GO:0042407
    label: cristae formation
proposed_new_terms: []
suggested_questions:
- question: Does the J domain of DNAJC11 recruit a mitochondrial HSP70 (e.g. HSPA9/mortalin) to the MIB complex, and is any co-chaperone activity required for cristae organization?
- question: What are the distinct functions of the differentially localized DNAJC11 isoforms (outer membrane vs inner-membrane/IMS forms)?
suggested_experiments:
- description: Reconstitute or immunopurify the MIB complex with wild-type versus J-domain-mutant DNAJC11 and assess MICOS/SAM assembly, cristae junction morphology (by electron microscopy), and recruitment of mitochondrial HSP70.
- description: Isoform-specific knockout/rescue in human cells followed by quantitative proteomics and cryo-EM tomography to define which DNAJC11 isoform supports cristae architecture and MICOS stability.