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.