TTC19

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005743 mitochondrial inner membrane	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred localization of TTC19 to the mitochondrial inner membrane. This is consistent with experimental evidence that TTC19 is an inner-membrane-embedded Complex III assembly factor and is the correct, specific compartment for this protein. Reason: The inner-membrane localization is directly supported by experimental data (PMID:21278747) and by the protein's role as a Complex III assembly factor; the IBA call is appropriate and at the correct level of specificity. Supporting Evidence: PMID:21278747 inner mitochondrial membrane as part of two high-molecular-weight complexes
GO:0034551 mitochondrial respiratory chain complex III assembly	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred involvement of TTC19 in mitochondrial respiratory chain complex III assembly. This matches the experimentally established core function of TTC19 as a Complex III assembly/maintenance factor and is supported by the Drosophila ortholog. Reason: This is the core biological process for TTC19, supported experimentally in humans and flies (PMID:21278747). The IBA term is at the appropriate level of specificity and is retained as a core function. Supporting Evidence: PMID:21278747 TTC19 is a putative cIII assembly factor
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation of inner-membrane localization derived from the UniProt Subcellular Location vocabulary mapping. It agrees with the curated experimental localization. Reason: Correct and consistent with experimental IDA evidence (PMID:21278747); the SubCell-derived IEA is at the correct level of specificity. Supporting Evidence: file:human/TTC19/TTC19-uniprot.txt Mitochondrion inner membrane
GO:0034551 mitochondrial respiratory chain complex III assembly	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation mapping the TTC19 InterPro signature (IPR040395) to mitochondrial respiratory chain complex III assembly. This matches the experimentally established function. Reason: The InterPro family is TTC19-specific (IPR040395 TTC19) and the mapping to Complex III assembly is biologically correct and supported by experimental evidence (PMID:21278747). Supporting Evidence: PMID:21278747 TTC19 is a putative cIII assembly factor
GO:0005515 protein binding	IPI PMID:16713569 A protein-protein interaction network for human inherited at...	MARK AS OVER ANNOTATED	Summary: Binary interaction of TTC19 captured in a yeast two-hybrid interactome for inherited ataxias (partner ATXN1, P54253). Bare "protein binding" is uninformative about molecular function. Reason: GO:0005515 "protein binding" does not convey a specific molecular function and is derived from a large-scale interaction screen. Per curation guidance, bare protein-binding IPIs are retained but flagged as over-annotated rather than removed; the informative function is captured by the Complex III assembly annotations. Supporting Evidence: PMID:16713569 protein-protein interactions using a stringent yeast two-hybrid screen
GO:0005515 protein binding	IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv...	MARK AS OVER ANNOTATED	Summary: Interaction of TTC19 reported in a skeletal-muscle (LGMD) interactome dataset (partner TCAP, O15273). Bare "protein binding" is uninformative about TTC19's molecular function. Reason: A high-throughput interactome-derived protein-binding IPI; retained but marked as over-annotated because it adds no specific functional information beyond the curated Complex III role. Supporting Evidence: PMID:23414517 LGMD interactome
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Interactions of TTC19 captured in a proteome-scale binary interactome map (HuRI-type screen). Bare "protein binding" is uninformative about molecular function. Reason: Large-scale interactome-derived protein-binding IPI; retained but flagged as over-annotated since it provides no specific molecular-function detail. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Interactions of TTC19 from a large-scale interactome ("protein communities and disease networks") study. Bare "protein binding" is uninformative about molecular function. Reason: High-throughput interactome-derived protein-binding IPI; retained but marked as over-annotated because it does not specify a molecular function. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease
GO:0005515 protein binding	IPI PMID:31617661 Global Interactome Mapping of Mitochondrial Intermembrane Sp...	MARK AS OVER ANNOTATED	Summary: TTC19 identified as a proximity/interaction partner (with HTRA2, O43464) in a BioID map of mitochondrial intermembrane-space proteases. Bare "protein binding" is uninformative. Reason: Proximity-labeling-derived protein-binding IPI; retained but flagged as over-annotated. It is consistent with TTC19's mitochondrial localization but adds no specific molecular function. Supporting Evidence: PMID:31617661 biotinylation (BioID) is used to map the interactomes
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Numerous binary interactions of TTC19 captured in a reference human binary interactome map. Bare "protein binding" is uninformative about molecular function. Reason: Large-scale binary-interactome-derived protein-binding IPI (many partners); retained but marked as over-annotated because it provides no specific molecular-function information. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: TTC19 interactions reported in a neurodegenerative-disease protein interaction network. Bare "protein binding" is uninformative about molecular function. Reason: Interactome-derived protein-binding IPI; retained but flagged as over-annotated as it conveys no specific molecular function. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: TTC19 interactions captured in cell-specific proteome-scale interactome networks (BioPlex). Bare "protein binding" is uninformative about molecular function. Reason: Large-scale AP-MS interactome-derived protein-binding IPI; retained but marked as over-annotated because it provides no specific molecular-function information. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: Immunofluorescence-based (Human Protein Atlas) localization of TTC19 to the mitochondrion. Correct but less specific than the inner-membrane annotation. Reason: Consistent with the established mitochondrial localization of TTC19. It is accurate though more general than the mitochondrial inner membrane annotation, which better captures the protein's precise location. Supporting Evidence: PMID:21278747 inner mitochondrial membrane as part of two high-molecular-weight complexes
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput identification of TTC19 in a high-confidence human mitochondrial proteome (MitoCoP). Confirms mitochondrial localization at the organelle level. Reason: TTC19 is a bona fide mitochondrial protein; this proteomics-based organelle-level localization is correct, though less specific than the inner-membrane annotation. Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
GO:0000281 mitotic cytokinesis	TAS PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr...	MARK AS OVER ANNOTATED	Summary: Proposed role for TTC19 in cytokinesis, as a ZFYVE26 (FYVE-CENT) binding partner interacting with the ESCRT-III subunit CHMP4B at the midbody. This is not the core mitochondrial function of TTC19 and is disputed. Reason: This assignment rests on a single study (PMID:20208530); UniProt records a CAUTION that the midbody localization underpinning this cytokinesis role could not be confirmed by others (PMID:21278747), and the well-established function of TTC19 is as a mitochondrial inner-membrane Complex III assembly factor. The annotation is retained but flagged as an over-annotation rather than removed, since the underlying interaction was experimentally reported. Supporting Evidence: PMID:20208530 TTC19, which in turn interacts with CHMP4B, an endosomal sorting file:human/TTC19/TTC19-uniprot.txt the midbody localization could not be
GO:0005515 protein binding	IPI PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr...	MARK AS OVER ANNOTATED	Summary: Interaction of TTC19 with ZFYVE26/FYVE-CENT (Q68DK2) and CHMP4B (Q9H444) reported in the cytokinesis study. Bare "protein binding" is uninformative about molecular function. Reason: A specific reported interaction, but captured only as the uninformative GO:0005515; retained per curation guidance but marked as over-annotated. The associated cytokinesis role is itself disputed (see UniProt CAUTION, PMID:21278747). Supporting Evidence: PMID:20208530 binding partner TTC19
GO:0005743 mitochondrial inner membrane	IDA PMID:21278747 Mutations in TTC19 cause mitochondrial complex III deficienc...	ACCEPT	Summary: Direct experimental evidence that TTC19 is embedded in the mitochondrial inner membrane, as part of high-molecular-weight complexes one of which coincides with Complex III. Reason: This is the primary experimental source establishing TTC19's inner-membrane localization and is a core, well-supported annotation. Supporting Evidence: PMID:21278747 inner mitochondrial membrane as part of two high-molecular-weight complexes, one of which coincides with cIII
GO:0005813 centrosome	TAS PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr...	MARK AS OVER ANNOTATED	Summary: Reported centrosomal localization of TTC19 during the cell cycle from the cytokinesis study. This is inconsistent with TTC19's established role as a mitochondrial inner-membrane protein. Reason: Based on a single study (PMID:20208530); UniProt notes a CAUTION that the associated midbody localization could not be confirmed by others (PMID:21278747), and TTC19 is firmly established as a mitochondrial inner-membrane protein. Flagged as over-annotation rather than removed, since the localization was experimentally reported. Supporting Evidence: file:human/TTC19/TTC19-uniprot.txt the midbody localization could not be PMID:20208530 recruits a centrosomal protein, FYVE-CENT (ZFYVE26), and its binding partner TTC19
GO:0030496 midbody	TAS PMID:20208530 PtdIns(3)P controls cytokinesis through KIF13A-mediated recr...	MARK AS OVER ANNOTATED	Summary: Reported recruitment of TTC19 to the midbody during cytokinesis. UniProt explicitly notes that this midbody localization could not be confirmed by others. Reason: Single-study localization (PMID:20208530) that is contradicted by follow-up work (PMID:21278747, per the UniProt CAUTION) and is inconsistent with TTC19's mitochondrial inner-membrane biology. Retained but flagged as over-annotation rather than removed. Supporting Evidence: file:human/TTC19/TTC19-uniprot.txt the midbody localization could not be PMID:20208530 Translocation of FYVE-CENT and TTC19 from the centrosome to
GO:0034551 mitochondrial respiratory chain complex III assembly	IMP PMID:21278747 Mutations in TTC19 cause mitochondrial complex III deficienc...	ACCEPT	Summary: Direct genetic/mutational evidence that loss of TTC19 causes Complex III deficiency with accumulation of cIII-specific assembly intermediates in humans and flies, establishing TTC19 as a Complex III assembly factor. Reason: This is the core, experimentally established function of TTC19 and is well supported by the disease-causing loss-of-function mutations and the Drosophila knockout phenotype. It is retained as the primary core function. Supporting Evidence: PMID:21278747 profound cIII deficiency and accumulation of cIII-specific assembly intermediates

Gene Description

Existing Annotations Review

Core Functions

Mitochondrial inner-membrane tetratricopeptide-repeat assembly/maintenance factor for respiratory Complex III (cytochrome bc1); required for turnover of UQCRFS1 (Rieske) N-terminal fragments to preserve Complex III integrity. Non-catalytic scaffold protein.

References

📚 Additional Documentation

Notes

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