C1QBP (also known as p32, gC1qR, HABP1) is a multifunctional, multicompartmental acidic homotrimeric protein with a distinctive donut-shaped structure. It belongs to the MAM33 family and localizes predominantly to the mitochondrial matrix, with additional pools at the cell surface, cytoplasm, and nucleus. The two primary core functions are: (1) mitochondrial translation support through binding mitochondrial RNAs (including m5C-modified RNAs) and association with mitoribosomes, essential for OXPHOS and cellular metabolic fitness; and (2) cell-surface receptor function for complement C1q (gC1qR), binding the globular heads of C1q to modulate complement activation and immune signaling. Biallelic C1QBP mutations cause combined oxidative phosphorylation deficiency 33 (COXPD33), confirming its essential mitochondrial role.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: C1QBP has been documented in the nucleus in specific contexts, including nuclear localization with POLGARF (PMID:32958672), translocation during HCMV infection (deep research), and co-localization with CBF-B for transcriptional corepression (PMID:15243141). Reason: Nuclear localization is well-documented though it represents a minor pool compared to mitochondria. The protein can function in the nucleus as a transcriptional corepressor and during viral infection. Supporting Evidence: PMID:15243141 Cellular localization by immunofluorescence staining revealed that p32 is present in the cell throughout the cytosol and nucleus, whereas CBF is present primarily in the nucleus. A portion of the p32 colocalizes with CBF-B in the nucleus. PMID:11083468 P32 (gClq-R) reactivity is also present... in nuclei of splenic lymphocytes file:human/C1QBP/C1QBP-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0042256 cytosolic ribosome assembly | IBA GO_REF:0000033 | ACCEPT | Summary: C1QBP participates in ribosome biogenesis by regulating binding of Nop52 and fibrillarin to preribosome particles (PMID:21536856). This involves the exchange of FBL for RRP1 in association with pre-ribosome particles. Reason: Supported by direct experimental evidence showing C1QBP involvement in ribosome maturation processes, though this is likely a secondary function compared to mitochondrial roles. Supporting Evidence: PMID:21536856 Splicing factor 2-associated protein p32 participates in ribosome biogenesis by regulating the binding of Nop52 and fibrillarin to preribosome particles. |
| GO:0001849 complement component C1q complex binding | IBA GO_REF:0000033 | ACCEPT | Summary: C1QBP was originally identified as the receptor for the globular heads of complement C1q (gC1qR). This is a core function supported by extensive literature (PMID:8195709, deep research from Ghebrehiwet 2024). Reason: This is one of the two primary core functions of C1QBP. The protein binds specifically to the globular heads of C1q, modulating complement activation and immune signaling at the cell surface. Supporting Evidence: PMID:8195709 This protein designated gC1q-R, was first isolated from Raji cells and was found to bind to the globular "heads" of C1q molecules |
| GO:0003714 transcription corepressor activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: C1QBP interacts with NF-YB (CBF-B) and inhibits CBF-mediated transcription activation in vitro (PMID:15243141). This represents a non-core secondary function. Reason: While experimentally supported, transcriptional corepression is not a core function of C1QBP. The primary functions are mitochondrial translation support and C1q receptor activity. This represents a secondary role when C1QBP is present in the nucleus. Supporting Evidence: PMID:15243141 p32 specifically inhibits CBF-mediated transcription activation. Altogether, our study identified p32 as a novel and specific corepressor of CBF-mediated transcription activation in vitro. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: C1QBP localizes to the plasma membrane as a peripheral membrane protein on the extracellular side, where it functions as the gC1qR receptor (PMID:8195709, PMID:8662673, PMID:12574814). Reason: Cell surface localization is well-established and critical for the receptor function of C1QBP in binding C1q, kininogens, and other plasma proteins. Supporting Evidence: PMID:11083468 strong P32 (gClq-R) reactivity is also present... on the cell surface of microvascular endothelial cells in pancreas and kidney |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Summary: C1QBP is present at the cell surface where it acts as a receptor for C1q and kininogens. Surface expression is enhanced upon platelet and monocyte activation (PMID:12574814). Reason: Cell surface localization is essential for C1QBP's receptor functions in complement and kinin pathways. Supporting Evidence: PMID:11083468 strong P32 (gClq-R) reactivity is also present... on the cell surface of pancreatic acinar cells... on the cell surface of microvascular endothelial cells |
| GO:0030449 regulation of complement activation | IBA GO_REF:0000033 | ACCEPT | Summary: C1QBP regulates complement activation by binding to the globular heads of C1q, thereby inhibiting C1 activation (PMID:8195709). This is a core function of the protein. Reason: This is a well-established core function directly linked to C1QBP's role as the gC1qR receptor. Supporting Evidence: PMID:8195709 This protein designated gC1q-R, was first isolated from Raji cells and was found to bind to the globular "heads" of C1q molecules |
| GO:0030984 kininogen binding | IBA GO_REF:0000033 | ACCEPT | Summary: C1QBP binds kininogen as part of its receptor function at the cell surface (PMID:8662673). In complex with KRT1, it serves as a high-affinity receptor for kininogen-1/HMWK. Reason: Kininogen binding is a core receptor function of C1QBP, positioning it at the intersection of complement and kinin pathways. Supporting Evidence: PMID:8662673 Isolation and characterization of the kininogen-binding protein p33 from endothelial cells. Identity with the gC1q receptor. |
| GO:0048025 negative regulation of mRNA splicing, via spliceosome | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: C1QBP (p32) regulates RNA splicing by inhibiting ASF/SF2 RNA binding and phosphorylation (PMID:10022843). This is a well-characterized secondary function. Reason: While experimentally validated, splicing regulation is not a core function of C1QBP. The primary functions are mitochondrial translation support and complement receptor activity. C1QBP was originally co-purified with SF2 but its role is regulatory rather than essential. Supporting Evidence: PMID:10022843 p32 inhibits ASF/SF2 function as both a splicing enhancer and splicing repressor protein by preventing stable ASF/SF2 interaction with RNA... p32 functions as an ASF/SF2 inhibitory factor, regulating ASF/SF2 RNA binding and phosphorylation. |
| GO:0002250 adaptive immune response | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Annotation based on UniProt keyword mapping (Adaptive immunity). C1QBP is involved in immune modulation through its C1q receptor function but is not directly part of adaptive immunity machinery. Reason: C1QBP modulates immune responses through complement pathway but is not directly involved in adaptive immune response mechanisms. The annotation is too general and imprecise. |
| GO:0002376 immune system process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Very broad term based on UniProt keyword. C1QBP participates in immune processes through complement modulation but this term is too general. Reason: While technically accurate that C1QBP participates in immune processes through complement and kinin pathways, this annotation is too broad to be informative. More specific annotations (complement activation, C1q binding) better capture its function. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: C1QBP can be secreted by activated lymphocytes and released from tumor cells as a soluble form (deep research). Reason: Secretion is documented in specific contexts (activated lymphocytes, tumor cells), supporting extracellular localization. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Duplicate of IBA annotation. Nuclear localization is documented. Reason: Consistent with IBA annotation and experimental evidence. Nuclear pools exist under specific conditions. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: C1QBP localizes to the nucleolus when coexpressed with POLGARF (PMID:32958672). This is a conditional localization. Reason: Nucleolar localization is supported by experimental evidence, though it requires interaction with POLGARF to prevent C1QBP maturation. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic pools of C1QBP are documented (PMID:15243141, PMID:11083468). Reason: Cytoplasmic localization is well-supported by immunostaining studies. Supporting Evidence: PMID:15243141 p32 is present in the cell throughout the cytosol and nucleus |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000120 | ACCEPT | Summary: C1QBP localizes predominantly to the mitochondrial matrix where it functions in mitochondrial translation (PMID:9305894, PMID:39019044). Reason: Mitochondrial matrix localization is the primary location of C1QBP and is essential for its core function in supporting OXPHOS. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Duplicate annotation. Plasma membrane localization is well-documented. Reason: Consistent with IBA annotation and receptor function. |
| GO:0006397 mRNA processing | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Based on UniProt mRNA processing keyword. C1QBP regulates splicing but this is a secondary function. Reason: C1QBP regulates splicing through ASF/SF2 inhibition but this is not its core function. Acceptable but should be noted as non-core. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This annotation is based on UniProt Apoptosis keyword. C1QBP interacts with HRK (PMID:15031724) and CDKN2A/smARF but it is NOT an evolved apoptotic factor. Its core functions are mitochondrial translation support and complement receptor activity. Reason: C1QBP is over-annotated for apoptotic process. While it can interact with pro-apoptotic proteins like HRK (PMID:15031724), this represents a downstream/pleiotropic effect rather than a core evolved function. The protein's primary roles are mitochondrial RNA binding/translation support and C1q receptor function. Any effects on apoptosis are indirect. Supporting Evidence: PMID:15031724 small interfering RNA-mediated knockdown of p32 conferred protection against Hrk-induced apoptosis |
| GO:0006958 complement activation, classical pathway | IEA GO_REF:0000043 | ACCEPT | Summary: C1QBP binds C1q and regulates complement activation. This is a core function. Reason: Direct involvement in complement activation through C1q binding is a core function of C1QBP. |
| GO:0006974 DNA damage response | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: C1QBP regulates homologous recombination by inhibiting MRE11 activity (PMID:31353207). In absence of DNA damage, it binds unphosphorylated MRE11 and RAD50, preventing MRN complex formation. Reason: While C1QBP has a documented role in DNA damage response through MRE11 regulation, this is not its primary evolved function. The mitochondrial and complement receptor roles are core. |
| GO:0008380 RNA splicing | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: C1QBP regulates splicing through ASF/SF2 inhibition (PMID:10022843). Reason: Splicing regulation is a secondary function. The protein was originally co-purified with SF2 but its primary roles are elsewhere. |
| GO:0042254 ribosome biogenesis | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: C1QBP participates in ribosome biogenesis through regulation of nucleolar protein binding to pre-ribosome particles (PMID:21536856). Reason: Ribosome biogenesis involvement is supported but is not the primary function. The mitochondrial translation role is more central. |
| GO:0045087 innate immune response | IEA GO_REF:0000043 | ACCEPT | Summary: C1QBP modulates innate immunity through complement C1q binding and regulation of RIG-I/MDA5 antiviral pathways (PMID:19164550). Reason: Innate immune modulation is well-supported through complement pathway and antiviral response regulation. |
| GO:0005515 protein binding | IPI PMID:10831594 Protein kinase C [micro] is regulated by the multifunctional... | REMOVE | Summary: Generic protein binding annotation from interaction with protein kinase C. The annotation is uninformative. Reason: 'Protein binding' is too general and uninformative. More specific MF terms should be used when available (e.g., protein kinase C binding). Supporting Evidence: PMID:10831594 is regulated by the multifunctional chaperon protein |
| GO:0005515 protein binding | IPI PMID:11086025 Interaction between complement receptor gC1qR and hepatitis ... | REMOVE | Summary: Interaction with HCV core protein documented. Uninformative generic term. Reason: 'Protein binding' is uninformative. The specific interaction with viral proteins could be captured with more specific terms. Supporting Evidence: PMID:11086025 Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. |
| GO:0005515 protein binding | IPI PMID:12034482 The N-terminal conserved domain of rubella virus capsid inte... | REMOVE | Summary: Interaction with Rubella virus capsid protein. Reason: Generic protein binding annotation is uninformative. Supporting Evidence: PMID:12034482 The N-terminal conserved domain of rubella virus capsid interacts with the C-terminal region of cellular p32 and overexpression of p32 enhances the viral infectivity. |
| GO:0005515 protein binding | IPI PMID:12220632 The cytoplasmic tail peptide sequence of membrane type-1 mat... | REMOVE | Summary: Interaction with MT1-MMP cytoplasmic tail. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:12220632 The cytoplasmic tail peptide sequence of membrane type-1 matrix metalloproteinase (MT1-MMP) directly binds to gC1qR, a compartment-specific chaperone-like regulatory protein. |
| GO:0005515 protein binding | IPI PMID:14743216 A physical and functional map of the human TNF-alpha/NF-kapp... | REMOVE | Summary: High-throughput mapping study. Reason: Generic protein binding from HTP study is uninformative. Supporting Evidence: PMID:14743216 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |
| GO:0005515 protein binding | IPI PMID:15031724 Physical and functional interaction between BH3-only protein... | REMOVE | Summary: Interaction with HRK (BH3-only protein). Reason: Generic protein binding. The interaction with HRK is documented but better captured by specific process terms. Supporting Evidence: PMID:15031724 verified specific interaction and colocalization of Hrk and p32, both of which depended on the presence of the highly conserved C-terminal region of p32 |
| GO:0005515 protein binding | IPI PMID:16721827 CDC2L5, a Cdk-like kinase with RS domain, interacts with the... | REMOVE | Summary: Interaction with CDK13 affecting splicing. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:16721827 CDC2L5, a Cdk-like kinase with RS domain, interacts with the ASF/SF2-associated protein p32 and affects splicing in vivo. |
| GO:0005515 protein binding | IPI PMID:17486078 The autophagic inducer smARF interacts with and is stabilize... | REMOVE | Summary: Interaction with CDKN2A/smARF. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:17486078 May 7. The autophagic inducer smARF interacts with and is stabilized by the mitochondrial p32 protein. |
| GO:0005515 protein binding | IPI PMID:18676636 Human p32 is a novel FOXC1-interacting protein that regulate... | REMOVE | Summary: Interaction with FOXC1. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:18676636 Epub 2008 Aug 1. Human p32 is a novel FOXC1-interacting protein that regulates FOXC1 transcriptional activity in ocular cells. |
| GO:0005515 protein binding | IPI PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by... | REMOVE | Summary: Interaction with MAVS for antiviral response regulation. Reason: Generic protein binding is uninformative. The functional consequence (RIG-I/MDA5 pathway inhibition) is better captured by specific BP terms. Supporting Evidence: PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria. |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | REMOVE | Summary: HTP protein interaction study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:21653829 Protein interactome reveals converging molecular pathways among autism disorders. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: HTP liver interactome study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:22118625 NONO and RALY proteins are required for YB-1 oxaliplatin ind... | REMOVE | Summary: Interaction study with YB-1 and related proteins. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:22118625 NONO and RALY proteins are required for YB-1 oxaliplatin induced resistance in colon adenocarcinoma cell lines. |
| GO:0005515 protein binding | IPI PMID:22238231 Binding of cellular p32 protein to the rubella virus P150 re... | REMOVE | Summary: Interaction with Rubella virus P150 replicase. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:22238231 Jan 13. Binding of cellular p32 protein to the rubella virus P150 replicase protein via PxxPxR motifs. |
| GO:0005515 protein binding | IPI PMID:23986595 A host YB-1 ribonucleoprotein complex is hijacked by hepatit... | REMOVE | Summary: Interaction with YB-1 in HCV replication context. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:23986595 A host YB-1 ribonucleoprotein complex is hijacked by hepatitis C virus for the control of NS3-dependent particle production. |
| GO:0005515 protein binding | IPI PMID:24955142 Exploration of panviral proteome: high-throughput cloning an... | REMOVE | Summary: Panviral proteome interaction study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:24955142 Exploration of panviral proteome: high-throughput cloning and functional implications in virus-host interactions. |
| GO:0005515 protein binding | IPI PMID:25497084 C1QBP negatively regulates the activation of oncoprotein YBX... | REMOVE | Summary: Interaction with YBX1 in renal cell carcinoma. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:25497084 C1QBP negatively regulates the activation of oncoprotein YBX1 in the renal cell carcinoma as revealed by interactomics analysis. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: TRAIL-induced apoptosis interactome study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy. |
| GO:0005515 protein binding | IPI PMID:26184334 Comprehensive Protein Interactome Analysis of a Key RNA Heli... | REMOVE | Summary: RNA helicase interactome study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:26184334 Comprehensive Protein Interactome Analysis of a Key RNA Helicase: Detection of Novel Stress Granule Proteins. |
| GO:0005515 protein binding | IPI PMID:26816005 Homologous Transcription Factors DUX4 and DUX4c Associate wi... | REMOVE | Summary: Interaction with DUX4. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:26816005 eCollection 2016. Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation. |
| GO:0005515 protein binding | IPI PMID:27499296 Mitochondrial Protein Interaction Mapping Identifies Regulat... | REMOVE | Summary: Mitochondrial protein interaction mapping. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:27499296 2016 Aug 4. Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Human interactome architecture study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:28565870 C1QBP is upregulated in colon cancer and binds to apolipopro... | REMOVE | Summary: Interaction with apolipoprotein A-I in colon cancer. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:28565870 Mar 21. C1QBP is upregulated in colon cancer and binds to apolipoprotein A-I. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: EGFR network rewiring study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D). |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Human binary protein interactome reference map. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Dual proteome-scale network study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: OpenCell endogenous tagging study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0005515 protein binding | IPI PMID:36882853 The double homeodomain protein DUX4c is associated with rege... | REMOVE | Summary: DUX4c interaction study in muscle regeneration. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:36882853 The double homeodomain protein DUX4c is associated with regenerating muscle fibers and RNA-binding proteins. |
| GO:0005515 protein binding | IPI PMID:8710908 Identification of the zinc-dependent endothelial cell bindin... | REMOVE | Summary: Interaction with factor XII and kininogen. Reason: Generic protein binding. The kininogen binding is better captured by GO:0030984 (kininogen binding). Supporting Evidence: PMID:8710908 Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular "heads" of C1q (gC1q-R). |
| GO:0005515 protein binding | IPI PMID:8900153 The binding protein for globular heads of complement C1q, gC... | REMOVE | Summary: Interaction with vitronectin. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:8900153 The binding protein for globular heads of complement C1q, gC1qR. |
| GO:0001849 complement component C1q complex binding | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of IBA annotation. C1q binding is a core function. Reason: Core function supported by multiple evidence lines. |
| GO:0005080 protein kinase C binding | IEA GO_REF:0000107 | ACCEPT | Summary: C1QBP interacts with protein kinase C (PMID:10831594). This represents a specific interaction. Reason: Specific binding annotation is more informative than generic protein binding. |
| GO:0005615 extracellular space | IEA GO_REF:0000107 | ACCEPT | Summary: C1QBP can be secreted and found in extracellular space. Reason: Secretion is documented for activated lymphocytes and tumor cells. |
| GO:0031690 adrenergic receptor binding | IEA GO_REF:0000107 | UNDECIDED | Summary: C1QBP interacts with alpha-1B adrenergic receptor (ADRA1B) based on ortholog transfer from rat. Reason: This annotation is based on ortholog transfer. The functional significance of adrenergic receptor binding for C1QBP is unclear and not validated in human. |
| GO:0048786 presynaptic active zone | IEA GO_REF:0000107 | UNDECIDED | Summary: Localization to presynaptic active zone based on rat ortholog data. Reason: This neuronal localization is based on ortholog transfer and not validated in human. The functional relevance is unclear. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | UNDECIDED | Summary: Localization to glutamatergic synapse based on rat ortholog data. Reason: Synaptic localization based on ortholog transfer. Not validated in human. |
| GO:0098982 GABA-ergic synapse | IEA GO_REF:0000107 | UNDECIDED | Summary: Localization to GABAergic synapse based on rat ortholog data. Reason: Synaptic localization based on ortholog transfer. Not validated in human. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | ACCEPT | Summary: Mitochondrial localization confirmed by HPA immunofluorescence. This is the predominant localization of C1QBP. Reason: Mitochondrial localization is the primary location and essential for the core mitochondrial translation support function. Supporting Evidence: PMID:11083468 Immunogold labeling of Raji lymphoma, CHO, human fibroblasts, HeLa and B-SC-1 cells shows reactivity primarily within mitochondria. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane localization confirmed by HPA immunofluorescence. Reason: Consistent with receptor function at cell surface. |
| GO:0000957 mitochondrial RNA catabolic process | IDA PMID:39019044 RNA 5-methylcytosine marks mitochondrial double-stranded RNA... | ACCEPT | Summary: C1QBP recognizes m5C-modified mitochondrial RNAs and promotes their degradation via recruitment of the mitochondrial degradosome complex. This is a recently discovered core function. Reason: This 2024 study reveals a key mechanism by which C1QBP regulates mitochondrial RNA quality control, directly supporting its core mitochondrial function. Supporting Evidence: PMID:39019044 Epub 2024 Jul 16. RNA 5-methylcytosine marks mitochondrial double-stranded RNAs for degradation and cytosolic release. |
| GO:0005759 mitochondrial matrix | IDA PMID:39019044 RNA 5-methylcytosine marks mitochondrial double-stranded RNA... | ACCEPT | Summary: Mitochondrial matrix localization confirmed in this 2024 study. Reason: Consistent with other evidence for predominant mitochondrial matrix localization. Supporting Evidence: PMID:39019044 Epub 2024 Jul 16. RNA 5-methylcytosine marks mitochondrial double-stranded RNAs for degradation and cytosolic release. |
| GO:0062153 C5-methylcytidine-containing RNA reader activity | IDA PMID:39019044 RNA 5-methylcytosine marks mitochondrial double-stranded RNA... | ACCEPT | Summary: C1QBP specifically recognizes and binds m5C-modified mitochondrial RNAs. This is a newly discovered molecular function that is central to its mitochondrial role. Reason: This represents a specific and informative molecular function directly linked to C1QBP's core mitochondrial role. Supporting Evidence: PMID:39019044 Epub 2024 Jul 16. RNA 5-methylcytosine marks mitochondrial double-stranded RNAs for degradation and cytosolic release. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput quantitative mitochondrial proteome study confirms C1QBP as a high-confidence mitochondrial protein. Reason: Consistent with extensive evidence for mitochondrial localization. Supporting Evidence: PMID:34800366 Epub 2021 Nov 19. Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. |
| GO:0004857 enzyme inhibitor activity | IDA PMID:31353207 C1QBP Promotes Homologous Recombination by Stabilizing MRE11... | KEEP AS NON CORE | Summary: C1QBP inhibits MRE11 nuclease activity by binding unphosphorylated MRE11 and preventing MRN complex formation. Reason: While experimentally demonstrated, this enzyme inhibitor activity related to DNA repair is not a core function of C1QBP. Supporting Evidence: PMID:31353207 Epub 2019 Jul 25. C1QBP Promotes Homologous Recombination by Stabilizing MRE11 and Controlling the Assembly and Activation of MRE11/RAD50/NBS1 Complex. |
| GO:2000042 negative regulation of double-strand break repair via homologous recombination | IDA PMID:31353207 C1QBP Promotes Homologous Recombination by Stabilizing MRE11... | KEEP AS NON CORE | Summary: C1QBP negatively regulates HR by inhibiting MRN complex formation and MRE11 activity in the absence of DNA damage. Reason: DNA repair regulation is not a core function of C1QBP. The mitochondrial and complement receptor roles are primary. Supporting Evidence: PMID:31353207 Epub 2019 Jul 25. C1QBP Promotes Homologous Recombination by Stabilizing MRE11 and Controlling the Assembly and Activation of MRE11/RAD50/NBS1 Complex. |
| GO:0005515 protein binding | IPI PMID:32958672 Unusually efficient CUG initiation of an overlapping reading... | REMOVE | Summary: Interaction with POLGARF leading to nucleolar localization. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:32958672 Unusually efficient CUG initiation of an overlapping reading frame in POLG mRNA yields novel protein POLGARF. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9645692 | ACCEPT | Summary: Reactome annotation for C1QBP promoting p14ARF translocation to mitochondrial matrix. Reason: Consistent with mitochondrial matrix localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645692 | ACCEPT | Summary: Reactome annotation for cytosolic pool of C1QBP involved in p14ARF pathway. Reason: Cytosolic localization is documented. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645694 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other evidence. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645766 | ACCEPT | Summary: Duplicate cytosol annotation from Reactome. Reason: Consistent with other evidence. |
| GO:0005515 protein binding | IPI PMID:18191643 Novel tyrosine phosphorylated and cardiolipin-binding protei... | REMOVE | Summary: Interaction with PLEKHN1. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:18191643 Novel tyrosine phosphorylated and cardiolipin-binding protein CLPABP functions as mitochondrial RNA granule. |
| GO:0005759 mitochondrial matrix | IDA PMID:9305894 p32 protein, a splicing factor 2-associated protein, is loca... | ACCEPT | Summary: Original demonstration of C1QBP mitochondrial matrix localization and importance for OXPHOS maintenance. Reason: This landmark study established the mitochondrial function of C1QBP. Supporting Evidence: PMID:9305894 p32 protein, a splicing factor 2-associated protein, is localized in mitochondrial matrix and is functionally important in maintaining oxidative phosphorylation. |
| GO:0005739 mitochondrion | IDA PMID:11083468 Localization of P32 protein (gC1q-R) in mitochondria and at ... | ACCEPT | Summary: Immunogold electron microscopy confirming primary mitochondrial localization with specific extramitochondrial locations. Reason: Strong experimental support for predominant mitochondrial localization. Supporting Evidence: PMID:11083468 Immunogold labeling of Raji lymphoma, CHO, human fibroblasts, HeLa and B-SC-1 cells shows reactivity primarily within mitochondria. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158218 | ACCEPT | Summary: Reactome annotation for kinin pathway at plasma membrane. Reason: Plasma membrane localization for receptor function is well-established. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158251 | ACCEPT | Summary: Duplicate Reactome annotation for kinin pathway. Reason: Consistent with other evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158311 | ACCEPT | Summary: Duplicate Reactome annotation for kinin pathway. Reason: Consistent with other evidence. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158313 | ACCEPT | Summary: Reactome annotation for factor XII activation. Reason: Consistent with C1QBP role in kinin/complement pathways. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-158354 | ACCEPT | Summary: Reactome annotation for kininogen binding. Reason: Consistent with receptor function. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:15243141 Human p32, interacts with B subunit of the CCAAT-binding fac... | KEEP AS NON CORE | Summary: C1QBP inhibits CBF/NF-Y mediated transcription activation in vitro. Reason: Transcriptional regulation is a secondary function when C1QBP is present in the nucleus. Not a core function. Supporting Evidence: PMID:15243141 p32 specifically inhibits CBF-mediated transcription activation |
| GO:0003714 transcription corepressor activity | IDA PMID:15243141 Human p32, interacts with B subunit of the CCAAT-binding fac... | KEEP AS NON CORE | Summary: C1QBP acts as transcriptional corepressor for CBF/NF-Y. Reason: Secondary function in nucleus. Not a core function. Supporting Evidence: PMID:15243141 our study identified p32 as a novel and specific corepressor of CBF-mediated transcription activation in vitro |
| GO:0005634 nucleus | IDA PMID:15243141 Human p32, interacts with B subunit of the CCAAT-binding fac... | ACCEPT | Summary: Nuclear localization demonstrated by immunofluorescence. Reason: Consistent with other evidence for nuclear pools. Supporting Evidence: PMID:15243141 p32 is present in the cell throughout the cytosol and nucleus |
| GO:0005829 cytosol | IDA PMID:15243141 Human p32, interacts with B subunit of the CCAAT-binding fac... | ACCEPT | Summary: Cytosolic localization demonstrated by immunofluorescence. Reason: Consistent with other evidence. Supporting Evidence: PMID:15243141 Human p32, interacts with B subunit of the CCAAT-binding factor, CBF/NF-Y, and inhibits CBF-mediated transcription activation in vitro. |
| GO:0008134 transcription factor binding | IDA PMID:15243141 Human p32, interacts with B subunit of the CCAAT-binding fac... | KEEP AS NON CORE | Summary: C1QBP binds to NF-YB (CBF-B) transcription factor subunit. Reason: Transcription factor binding is related to the secondary transcriptional corepressor function. Supporting Evidence: PMID:15243141 Human p32, interacts with B subunit of the CCAAT-binding factor, CBF/NF-Y, and inhibits CBF-mediated transcription activation in vitro. |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:15031724 Physical and functional interaction between BH3-only protein... | MARK AS OVER ANNOTATED | Summary: C1QBP interaction with HRK leads to positive regulation of apoptosis when HRK is expressed. However, p32 knockdown actually protected against Hrk-induced apoptosis, suggesting p32 facilitates HRK-mediated apoptosis rather than being a direct apoptotic factor. Reason: This annotation overstates C1QBP's role in apoptosis. C1QBP is not an evolved apoptotic factor. It interacts with HRK and may facilitate HRK-induced apoptosis in specific contexts, but its core functions are mitochondrial translation support and complement receptor activity. Any apoptotic effects are downstream/pleiotropic. Supporting Evidence: PMID:15031724 small interfering RNA-mediated knockdown of p32 conferred protection against Hrk-induced apoptosis |
| GO:0048025 negative regulation of mRNA splicing, via spliceosome | IDA PMID:10022843 The splicing factor-associated protein, p32, regulates RNA s... | KEEP AS NON CORE | Summary: C1QBP inhibits ASF/SF2 RNA binding and phosphorylation, negatively regulating splicing. Reason: Splicing regulation is a well-documented secondary function but not the core role of C1QBP. Supporting Evidence: PMID:10022843 p32 inhibits ASF/SF2 function as both a splicing enhancer and splicing repressor protein by preventing stable ASF/SF2 interaction with RNA |
| GO:0001849 complement component C1q complex binding | IDA PMID:8195709 Isolation, cDNA cloning, and overexpression of a 33-kD cell ... | ACCEPT | Summary: Original identification of C1QBP as gC1qR, binding globular heads of C1q. Reason: This is a core function established in the seminal paper. Supporting Evidence: PMID:8195709 Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q. |
| GO:0003729 mRNA binding | ISS GO_REF:0000024 | ACCEPT | Summary: mRNA binding inferred from mouse ortholog. C1QBP binds mitochondrial RNAs to support translation. Reason: RNA binding is part of the core mitochondrial translation support function. |
| GO:0005540 hyaluronic acid binding | IDA PMID:8567680 Molecular cloning of human fibroblast hyaluronic acid-bindin... | KEEP AS NON CORE | Summary: C1QBP (HABP1) was identified as a hyaluronic acid-binding protein. Reason: Hyaluronic acid binding is documented but not a core function. May be relevant in specific extracellular contexts. Supporting Evidence: PMID:8567680 Molecular cloning of human fibroblast hyaluronic acid-binding protein confirms its identity with P-32, a protein co-purified with splicing factor SF2. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasmic localization from ortholog inference. Reason: Consistent with experimental evidence for cytoplasmic pools. |
| GO:0005739 mitochondrion | IDA PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by... | ACCEPT | Summary: Mitochondrial localization confirmed in context of antiviral response study (MAVS interaction). Reason: Consistent with predominant mitochondrial localization. Supporting Evidence: PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria. |
| GO:0009986 cell surface | IDA PMID:17881511 HCV core protein interaction with gC1q receptor inhibits Th1... | ACCEPT | Summary: Cell surface localization in context of HCV core protein interaction study. Reason: Cell surface localization is essential for receptor function. Supporting Evidence: PMID:17881511 HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production. |
| GO:0016020 membrane | IDA PMID:8662673 Isolation and characterization of the kininogen-binding prot... | ACCEPT | Summary: Membrane association documented in kininogen binding study. Reason: Consistent with peripheral membrane protein localization. Supporting Evidence: PMID:8662673 Isolation and characterization of the kininogen-binding protein p33 from endothelial cells. |
| GO:0030449 regulation of complement activation | IDA PMID:8195709 Isolation, cDNA cloning, and overexpression of a 33-kD cell ... | ACCEPT | Summary: C1QBP regulates complement by binding C1q globular heads. Reason: Core function established in seminal paper. Supporting Evidence: PMID:8195709 Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q. |
| GO:0030984 kininogen binding | IDA PMID:8662673 Isolation and characterization of the kininogen-binding prot... | ACCEPT | Summary: C1QBP/p33 identified as kininogen-binding protein on endothelial cells. Reason: Kininogen binding is a core receptor function. Supporting Evidence: PMID:8662673 Isolation and characterization of the kininogen-binding protein p33 from endothelial cells. |
| GO:0031690 adrenergic receptor binding | ISS GO_REF:0000024 | UNDECIDED | Summary: Adrenergic receptor binding from ortholog inference. Reason: Functional significance in human is unclear. |
| GO:0032689 negative regulation of type II interferon production | IDA PMID:17881511 HCV core protein interaction with gC1q receptor inhibits Th1... | KEEP AS NON CORE | Summary: C1QBP (via HCV core protein interaction) suppresses IFN-gamma production. Reason: Immune modulation is documented but represents downstream effect of C1QBP's receptor function rather than a core role. Supporting Evidence: PMID:17881511 HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production. |
| GO:0032695 negative regulation of interleukin-12 production | IDA PMID:16177118 gC1q receptor ligation selectively down-regulates human IL-1... | KEEP AS NON CORE | Summary: gC1qR ligation downregulates IL-12 production through PI3K pathway. Reason: IL-12 regulation is a downstream consequence of receptor function. Supporting Evidence: PMID:16177118 gC1q receptor ligation selectively down-regulates human IL-12 production through activation of the phosphoinositide 3-kinase pathway. |
| GO:0032695 negative regulation of interleukin-12 production | IDA PMID:17881511 HCV core protein interaction with gC1q receptor inhibits Th1... | KEEP AS NON CORE | Summary: Duplicate annotation for IL-12 regulation. Reason: Same as above - downstream effect of receptor function. Supporting Evidence: PMID:17881511 HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production. |
| GO:0039534 negative regulation of MDA-5 signaling pathway | IDA PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by... | KEEP AS NON CORE | Summary: C1QBP inhibits MDA5 (IFIH1) antiviral signaling through MAVS interaction. Reason: Antiviral response modulation is a documented secondary function. Supporting Evidence: PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria. |
| GO:0039536 negative regulation of RIG-I signaling pathway | IDA PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by... | KEEP AS NON CORE | Summary: C1QBP inhibits RIG-I antiviral signaling through MAVS interaction. Reason: Antiviral response modulation is a documented secondary function. Supporting Evidence: PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria. |
| GO:0042256 cytosolic ribosome assembly | IMP PMID:21536856 Splicing factor 2-associated protein p32 participates in rib... | KEEP AS NON CORE | Summary: C1QBP participates in ribosome biogenesis by regulating nucleolar protein binding to pre-ribosome particles. Reason: Ribosome biogenesis is a secondary function. Supporting Evidence: PMID:21536856 Epub 2011 May 2. Splicing factor 2-associated protein p32 participates in ribosome biogenesis by regulating the binding of Nop52 and fibrillarin to preribosome particles. |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:16177118 gC1q receptor ligation selectively down-regulates human IL-1... | KEEP AS NON CORE | Summary: gC1qR ligation activates PI3K-AKT pathway. Reason: PI3K signaling is a downstream consequence of receptor ligation. Supporting Evidence: PMID:16177118 gC1q receptor ligation selectively down-regulates human IL-12 production through activation of the phosphoinositide 3-kinase pathway. |
| GO:0045785 positive regulation of cell adhesion | IMP PMID:20810993 An alternative role of C1q in cell migration and tissue remo... | KEEP AS NON CORE | Summary: C1q-C1QBP interaction promotes cell adhesion in trophoblast invasion. Reason: Cell adhesion regulation is a downstream consequence of C1q binding. Supporting Evidence: PMID:20810993 Sep 1. An alternative role of C1q in cell migration and tissue remodeling: contribution to trophoblast invasion and placental development. |
| GO:0050687 negative regulation of defense response to virus | IMP PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by... | KEEP AS NON CORE | Summary: C1QBP inhibits RIG-I and MDA5 antiviral pathways. Reason: Antiviral response modulation is a secondary function. Supporting Evidence: PMID:19164550 Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:16177118 gC1q receptor ligation selectively down-regulates human IL-1... | KEEP AS NON CORE | Summary: gC1qR ligation activates PI3K-AKT signaling. Reason: Downstream signaling consequence of receptor function. Supporting Evidence: PMID:16177118 gC1q receptor ligation selectively down-regulates human IL-12 production through activation of the phosphoinositide 3-kinase pathway. |
| GO:0070131 positive regulation of mitochondrial translation | ISS GO_REF:0000024 | ACCEPT | Summary: C1QBP supports mitochondrial translation through RNA binding and mitoribosome association. This is a core function. Reason: This is one of the two core functions of C1QBP - essential for OXPHOS and confirmed by disease mutations causing COXPD33. |
| GO:0090023 positive regulation of neutrophil chemotaxis | IDA PMID:9461517 C1q-mediated chemotaxis by human neutrophils: involvement of... | KEEP AS NON CORE | Summary: C1q-mediated chemotaxis of neutrophils involves gC1qR and G-protein signaling. Reason: Chemotaxis regulation is a downstream consequence of C1q receptor function. Supporting Evidence: PMID:9461517 C1q-mediated chemotaxis by human neutrophils: involvement of gClqR and G-protein signalling mechanisms. |
| GO:0097177 mitochondrial ribosome binding | ISS GO_REF:0000024 | ACCEPT | Summary: C1QBP associates with mitoribosomes to support mitochondrial translation. Reason: Mitoribosome binding is integral to the core mitochondrial translation support function. |
| GO:1900026 positive regulation of substrate adhesion-dependent cell spreading | IMP PMID:11859136 Cooperation of C1q receptors and integrins in C1q-mediated e... | KEEP AS NON CORE | Summary: C1q receptors including C1QBP cooperate with integrins in endothelial cell adhesion and spreading. Reason: Cell spreading regulation is a downstream effect of C1q binding. Supporting Evidence: PMID:11859136 Cooperation of C1q receptors and integrins in C1q-mediated endothelial cell adhesion and spreading. |
| GO:1901165 positive regulation of trophoblast cell migration | IMP PMID:20810993 An alternative role of C1q in cell migration and tissue remo... | KEEP AS NON CORE | Summary: C1q-C1QBP axis promotes trophoblast migration in placental development. Reason: Trophoblast migration is a developmental context-specific consequence of C1q binding. Supporting Evidence: PMID:20810993 Sep 1. An alternative role of C1q in cell migration and tissue remodeling: contribution to trophoblast invasion and placental development. |
| GO:2000510 positive regulation of dendritic cell chemotaxis | IMP PMID:16140380 Chemotaxis of human monocyte-derived dendritic cells to comp... | KEEP AS NON CORE | Summary: C1q-mediated dendritic cell chemotaxis involves gC1qR. Reason: Chemotaxis regulation is a downstream consequence of C1q receptor function. Supporting Evidence: PMID:16140380 2005 Sep 2. Chemotaxis of human monocyte-derived dendritic cells to complement component C1q is mediated by the receptors gC1qR and cC1qR. |
| GO:0016020 membrane | IDA PMID:11290596 Expression and colocalization of cytokeratin 1 and urokinase... | ACCEPT | Summary: Membrane localization with cytokeratin 1 and urokinase receptor on endothelial cells. Reason: Membrane association is consistent with cell surface receptor function. Supporting Evidence: PMID:11290596 Expression and colocalization of cytokeratin 1 and urokinase plasminogen activator receptor on endothelial cells. |
| GO:0005886 plasma membrane | TAS PMID:8195709 Isolation, cDNA cloning, and overexpression of a 33-kD cell ... | ACCEPT | Summary: Original description of C1QBP as cell surface glycoprotein. Reason: Foundational evidence for cell surface localization. Supporting Evidence: PMID:8195709 Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q. |
| GO:0006955 immune response | TAS PMID:8195709 Isolation, cDNA cloning, and overexpression of a 33-kD cell ... | KEEP AS NON CORE | Summary: General immune response annotation from seminal paper. Reason: Very broad term. More specific annotations (complement activation, C1q binding) better capture the function. Supporting Evidence: PMID:8195709 Isolation, cDNA cloning, and overexpression of a 33-kD cell surface glycoprotein that binds to the globular "heads" of C1q. |
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