DNAJC13

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006898 receptor-mediated endocytosis	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic (IBA) annotation reflecting the gene's historical name (RME-8, required for receptor-mediated endocytosis), originally defined in C. elegans yolk uptake. In human cells DNAJC13/RME-8 acts on early endosomes downstream of internalization (sorting, recycling and degradation) rather than at the plasma-membrane internalization step per se, so this is a broadly correct but non-core process annotation. Reason: The family-level receptor-mediated endocytosis term is supported by orthology and the gene's role in endocytic trafficking, but DNAJC13's documented site of action is the endosome (recycling and degradative sorting), not the internalization step; it is a peripheral process relative to its core endosomal co-chaperone function. Supporting Evidence: PMID:18256511 hRME is primarily involved in membrane trafficking through early endosomes, but not through degradative organelles, such as multivesicular bodies and late endosomes.
GO:0005769 early endosome	IEA GO_REF:0000044	ACCEPT	Summary: Automated SubCell localization to early endosome, redundant with and consistent with the experimentally supported (EXP/IDA) early-endosome localization. Reason: DNAJC13 partially colocalizes with early endosomal markers and is its principal site of action; the IEA term agrees with stronger experimental evidence. Supporting Evidence: PMID:18256511 It partially colocalized with several early endosomal markers, but not with late endosomal markers
GO:0007032 endosome organization	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation of endosome organization, redundant with the experimentally supported IMP annotation of the same term (PMID:24643499); DNAJC13 controls endosomal membrane tubulation and SNX1 dynamics. Reason: Corroborated by direct experimental evidence that loss of DNAJC13/RME-8 alters endosomal tubulation and SNX1 membrane association; a core biological process for this gene. Supporting Evidence: PMID:24643499 Loss of RME-8 causes altered kinetics of SNX1 membrane association and a pronounced increase in highly branched endosomal tubules.
GO:0010008 endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Automated SubCell localization to endosome membrane, redundant with the experimentally supported (IDA) endosome-membrane localization. Reason: DNAJC13 is a peripheral endosome-membrane protein; consistent with IDA evidence. Supporting Evidence: file:human/DNAJC13/DNAJC13-uniprot.txt Endosome membrane {ECO:0000269\|PubMed:24643499}.
GO:0031901 early endosome membrane	IEA GO_REF:0000044	ACCEPT	Summary: Automated SubCell localization to early endosome membrane, redundant with the experimentally supported (IDA) annotation of the same term. Reason: DNAJC13 associates peripherally with early endosome membranes; agrees with IDA evidence. Supporting Evidence: file:human/DNAJC13/DNAJC13-uniprot.txt Early endosome membrane {ECO:0000305}; Peripheral membrane protein
GO:2000641 regulation of early endosome to late endosome transport	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation, redundant with the experimentally supported IMP annotation of the same term; DNAJC13 regulates EGF/EGFR transit toward degradation. Reason: Supported by direct evidence that DNAJC13 controls EGF/EGFR sorting from early endosomes toward the degradative pathway; a genuine process for this gene. Supporting Evidence: PMID:18307993 RME-8 depletion leads to decreased levels of epidermal growth factor receptor (EGFR)
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	KEEP AS NON CORE	Summary: High-throughput interaction capturing the DNAJC13-SCAMP1 (O15126) interaction also recorded in the UniProt INTERACTION block. The bare protein binding term is uninformative. Reason: Records a real interaction (with SCAMP1, a secretory carrier membrane protein) but GO:0005515 is uninformative and not part of the core endosomal co-chaperone function; not elevated to core per curation guidelines. Supporting Evidence: file:human/DNAJC13/DNAJC13-uniprot.txt O75165; O15126: SCAMP1; NbExp=3; IntAct=EBI-4324603, EBI-954338;
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 the DNAJC13-SCAMP1 (O15126) interaction. The bare protein binding term is uninformative. Reason: Real but uninformative high-throughput interaction (SCAMP1); not core and not elevated per curation guidelines. Supporting Evidence: file:human/DNAJC13/DNAJC13-uniprot.txt O75165; O15126: SCAMP1; NbExp=3; IntAct=EBI-4324603, EBI-954338;
GO:0005769 early endosome	EXP PMID:18256511 Human RME-8 is involved in membrane trafficking through earl...	ACCEPT	Summary: Experimental (EXP) localization of DNAJC13/RME-8 to early endosomes by colocalization with early endosomal markers and immunoelectron microscopy. Reason: Direct experimental evidence places DNAJC13 at early endosomes, its principal site of action; a core cellular-component annotation. Supporting Evidence: PMID:18256511 It partially colocalized with several early endosomal markers, but not with late endosomal markers, consistent with observations by immunoelectron microscopy.
GO:0001649 osteoblast differentiation	HDA PMID:16210410 Differential expression profiling of membrane proteins by qu...	MARK AS OVER ANNOTATED	Summary: Annotation derived from a quantitative membrane-proteomics study of a mesenchymal stem-cell line undergoing osteoblast differentiation; DNAJC13 was detected as a differentially expressed membrane protein, not shown to function in osteoblast differentiation. Reason: This is an expression-correlation (HDA) observation from a differentiation proteomics screen, not evidence that DNAJC13 plays a role in osteoblast differentiation; over-annotation relative to the gene's endosomal function. Supporting Evidence: file:human/DNAJC13/DNAJC13-goa.tsv GO:0001649 osteoblast differentiation biological_process ECO:0007005 HDA PMID:16210410
GO:0016020 membrane	HDA PMID:16210410 Differential expression profiling of membrane proteins by qu...	KEEP AS NON CORE	Summary: High-throughput membrane-proteomics detection of DNAJC13 in a membrane fraction. A generic membrane localization consistent with its peripheral endosome-membrane association. Reason: Correct but uninformative generic localization; the precise compartment (early endosome membrane) is captured by more specific annotations. Supporting Evidence: file:human/DNAJC13/DNAJC13-goa.tsv GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:16210410
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6798739	KEEP AS NON CORE	Summary: Reactome annotation from the neutrophil-degranulation pathway placing DNAJC13 at the plasma membrane. This reflects bulk granule/membrane proteome curation, not DNAJC13's core endosomal function. Reason: Curated TAS localization from a neutrophil degranulation pathway; peripheral to and not representative of DNAJC13's principal early-endosome site of action. Supporting Evidence: file:human/DNAJC13/DNAJC13-goa.tsv GO:0005886 plasma membrane cellular_component ECO:0000304 TAS Reactome:R-HSA-6798739
GO:0005886 plasma membrane	TAS Reactome:R-HSA-6798743	KEEP AS NON CORE	Summary: Second Reactome (neutrophil degranulation) plasma-membrane annotation, redundant with the R-HSA-6798739 entry. Reason: Curated TAS localization from neutrophil degranulation; peripheral to the core endosomal function. Supporting Evidence: file:human/DNAJC13/DNAJC13-goa.tsv GO:0005886 plasma membrane cellular_component ECO:0000304 TAS Reactome:R-HSA-6798743
GO:0030667 secretory granule membrane	TAS Reactome:R-HSA-6798743	KEEP AS NON CORE	Summary: Reactome neutrophil-degranulation annotation placing DNAJC13 in the secretory granule membrane. Reflects bulk granule-proteome curation rather than a defined granule function. Reason: Curated TAS localization from a degranulation pathway; specialized context peripheral to DNAJC13's core endosomal co-chaperone role. Supporting Evidence: file:human/DNAJC13/DNAJC13-goa.tsv GO:0030667 secretory granule membrane cellular_component ECO:0000304 TAS Reactome:R-HSA-6798743
GO:0035577 azurophil granule membrane	TAS Reactome:R-HSA-6798739	KEEP AS NON CORE	Summary: Reactome neutrophil-degranulation annotation placing DNAJC13 in the azurophil granule membrane. Reflects bulk granule-proteome curation. Reason: Curated TAS localization from a degranulation pathway; specialized context peripheral to the core endosomal function. Supporting Evidence: file:human/DNAJC13/DNAJC13-goa.tsv GO:0035577 azurophil granule membrane cellular_component ECO:0000304 TAS Reactome:R-HSA-6798739
GO:0005515 protein binding	IPI PMID:24643499 RME-8 coordinates the activity of the WASH complex with the ...	KEEP AS NON CORE	Summary: Curated interactions with WASH-complex subunits (WASHC2C/FAM21 A8K0Z3, WASHC5/strumpellin Q12768, WASHC2A/FAM21A Q9Y4E1). The bare protein binding term is uninformative, but these interactions are biologically meaningful and underpin DNAJC13's coordination of the WASH complex with retromer. Reason: Records real, functionally relevant WASH-complex interactions; however GO:0005515 itself is uninformative and is kept non-core (the functional consequence is captured by the endosome organization process annotation). Supporting Evidence: PMID:24643499 we show that FAM21 also binds to the SNX1-interacting DNAJ protein RME-8.
GO:0007032 endosome organization	IMP PMID:24643499 RME-8 coordinates the activity of the WASH complex with the ...	ACCEPT	Summary: IMP evidence that loss of DNAJC13/RME-8 dysregulates endosomal membrane tubulation and SNX1 dynamics, demonstrating a direct role in organizing the endosomal compartment. Reason: Strong loss-of-function evidence that DNAJC13 controls endosomal tubulation/SNX1 dynamics; a core biological process for this gene. Supporting Evidence: PMID:24643499 Loss of RME-8 causes altered kinetics of SNX1 membrane association and a pronounced increase in highly branched endosomal tubules.
GO:0010008 endosome membrane	IDA PMID:24643499 RME-8 coordinates the activity of the WASH complex with the ...	ACCEPT	Summary: Direct (IDA) evidence localizing DNAJC13 to endosome membranes. Reason: Direct experimental localization to the endosome membrane, the site of DNAJC13 action. Supporting Evidence: file:human/DNAJC13/DNAJC13-uniprot.txt Endosome membrane {ECO:0000269\|PubMed:24643499}.
GO:0031901 early endosome membrane	IDA PMID:18256511 Human RME-8 is involved in membrane trafficking through earl...	ACCEPT	Summary: Direct (IDA) localization of DNAJC13/RME-8 to early endosome membranes via its N-terminal membrane-association region. Reason: Direct experimental localization to the early endosome membrane; a core cellular component for this peripheral membrane protein. Supporting Evidence: PMID:18256511 hRME-8 was found to be a peripheral protein that was tightly associated with the membrane via its N-terminal region.
GO:0071203 WASH complex	IDA PMID:24643499 RME-8 coordinates the activity of the WASH complex with the ...	ACCEPT	Summary: Colocalization of DNAJC13 with the WASH complex, consistent with its binding to FAM21 (WASHC2) and its role in coordinating WASH activity with retromer-mediated sorting. Reason: Supported by direct colocalization and FAM21 binding; the colocalizes_with qualifier appropriately reflects that DNAJC13 associates with, but is not a stoichiometric subunit of, the WASH complex. Supporting Evidence: PMID:24643499 we show that FAM21 also binds to the SNX1-interacting DNAJ protein RME-8.
GO:2000641 regulation of early endosome to late endosome transport	IMP PMID:18256511 Human RME-8 is involved in membrane trafficking through earl...	ACCEPT	Summary: IMP evidence that C-terminal truncation of DNAJC13/RME-8 compromises the degradative pathway for EGF/EGFR (early endosome to late endosome transport). Reason: Loss-of-function evidence that DNAJC13 regulates trafficking of cargo from early endosomes toward degradation; a core process for this gene. Supporting Evidence: PMID:18256511 compromised endocytic pathways through early endosomes, i.e., recycling of transferrin and degradation of epidermal growth factor.
GO:2001135 regulation of endocytic recycling	IMP PMID:18256511 Human RME-8 is involved in membrane trafficking through earl...	ACCEPT	Summary: IMP evidence that DNAJC13/RME-8 regulates transferrin recycling (early endosome to recycling endosome transport). Reason: Loss-of-function evidence that DNAJC13 controls endocytic recycling of transferrin; a core process for this gene. Supporting Evidence: PMID:18256511 compromised endocytic pathways through early endosomes, i.e., recycling of transferrin and degradation of epidermal growth factor.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: High-throughput proteomics detection of DNAJC13 in a membrane fraction; generic localization consistent with its peripheral membrane association. Reason: Correct but uninformative generic localization superseded by specific early-endosome membrane annotations. Supporting Evidence: file:human/DNAJC13/DNAJC13-goa.tsv GO:0016020 membrane cellular_component ECO:0007005 HDA PMID:19946888
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: Detection of DNAJC13 in an extracellular-exosome proteomics dataset. Consistent with its endosomal localization (exosomes derive from endosomes) but does not denote a functional exosomal role. Reason: Bulk exosome-proteomics detection; plausible given endosomal origin of exosomes but peripheral to the gene's core function. Supporting Evidence: file:human/DNAJC13/DNAJC13-goa.tsv GO:0070062 extracellular exosome cellular_component ECO:0007005 HDA PMID:19056867
GO:0005765 lysosomal membrane	HDA PMID:17897319 Integral and associated lysosomal membrane proteins.	MARK AS OVER ANNOTATED	Summary: High-throughput lysosomal-membrane proteomics detection of DNAJC13. DNAJC13 acts on early endosomes and is explicitly reported NOT to act on degradative organelles, so this is likely contamination/co-fractionation rather than a genuine lysosomal pool. Reason: DNAJC13/RME-8 colocalizes with early but not late/degradative endosomal markers; a lysosomal-membrane localization from bulk proteomics conflicts with the experimental site of action and is likely co-fractionation. Supporting Evidence: PMID:18256511 It partially colocalized with several early endosomal markers, but not with late endosomal markers

Gene Description

Existing Annotations Review

Core Functions

Endosomal HSC70 (HSPA8) co-chaperone whose internal J domain stimulates HSC70 ATPase activity to drive clathrin dynamics and protein sorting on early endosome membranes.

Regulator of endosomal organization and protein sorting that controls endosomal membrane tubulation, SNX1 dynamics and cargo fate (transferrin recycling versus EGF/EGFR degradation), in part by linking the WASH complex (via FAM21/WASHC2) to the retromer SNX dimer.

References

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Notes

Pn Notes

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