CKB

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005576 extracellular region	IBA GO_REF:0000033	REMOVE	Summary: Phylogenetic (IBA) inference that B-CK is active in the extracellular region. B-CK is a cytosolic enzyme; it is detected in exosomes/secretome but is not active extracellularly. The "is_active_in extracellular region" call is an over-propagation and is biologically incorrect as a site of activity. Reason: Creatine kinase catalysis requires cytosolic ATP/ADP and creatine; the enzyme is not known to function in the extracellular region. Detection in secreted vesicles does not make the extracellular region a site of activity, so an "is_active_in extracellular region" assertion is incorrect. Aligned with the parallel CKM review, which REMOVEs the identical IBA annotation; genuine extracellular/exosome detection is retained separately under the extracellular-exosome annotations.
GO:0004111 creatine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Creatine kinase activity is the core molecular function of CKB, supported phylogenetically (IBA) and experimentally. Accept. Reason: This is the defining, experimentally established activity of CKB (EC 2.7.3.2); the IBA inference is consistent with direct assays. Supporting Evidence: PMID:8186255 The results showed residues Cys-283 and Arg-292 are essential for enzyme catalysis.
GO:0046314 phosphocreatine biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: The biological process corresponding to the forward (ATP -> phosphocreatine) direction of the creatine kinase reaction. Core process for CKB. Accept. Reason: Directly reflects the physiological left-to-right reaction direction catalyzed by CKB; consistent with the experimentally demonstrated activity.
GO:0003824 catalytic activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic root catalytic-activity term assigned by InterPro2GO. Correct but uninformative; subsumed by the specific creatine kinase activity annotation. Reason: A high-level ancestor of GO:0004111; adds no information beyond the specific molecular function and should not be retained as a meaningful annotation.
GO:0004111 creatine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (IEA) assignment of the core creatine kinase activity, consistent with experimental evidence. Accept (redundant with the experimental annotation but correct). Reason: Same correct core molecular function; electronic support via RHEA/EC mapping aligns with direct evidence.
GO:0005739 mitochondrion	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Electronic mitochondrion localization transferred by similarity from the mouse ortholog (Q04447) in the context of thermogenic-fat / futile-creatine-cycle biology. Human CKB is predominantly cytosolic; a mitochondrial pool is not directly demonstrated for human B-CK. Reason: B-CK is the cytosolic creatine kinase isoform; mitochondrial creatine kinase is a distinct gene product (uMtCK/CKMT1). The mitochondrial call is a by-similarity transfer specific to adipocyte thermogenesis and is not the core localization of human CKB.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic cytosol localization from the UniProt subcellular-location mapping. Correct core localization. Accept. Reason: B-CK is a cytosolic enzyme; consistent with IDA (HPA) and Reactome TAS annotations to cytosol.
GO:0005886 plasma membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic plasma-membrane call from UniProt subcellular-location mapping, reflecting peripheral recruitment of B-CK to membrane ATPase microcompartments (e.g. with KCC3). Real but peripheral, not the core compartment. Reason: CKB is not an integral membrane protein; it is recruited to the membrane to supply ATP to transporters such as KCC3 (PMID:18566107). Retain as a non-core peripheral localization.
GO:0016301 kinase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic kinase-activity parent from InterPro2GO; subsumed by the specific creatine kinase activity. Uninformative. Reason: Ancestor of GO:0004111; carries no information beyond the specific molecular function.
GO:0016772 transferase activity, transferring phosphorus-containing groups	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Generic phosphotransferase parent from InterPro2GO; subsumed by the specific creatine kinase activity. Uninformative. Reason: High-level ancestor of GO:0004111; redundant generic term.
GO:0016775 phosphotransferase activity, nitrogenous group as acceptor	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: The immediate parent class of creatine kinase activity (phosphotransfer to a nitrogenous/guanidino acceptor). Correct but redundant with the specific term. Reason: Direct ancestor of GO:0004111; the specific creatine kinase activity term is preferred and makes this generic term redundant.
GO:0046314 phosphocreatine biosynthetic process	IEA GO_REF:0000002	ACCEPT	Summary: Electronic assignment of the core phosphocreatine biosynthetic process, consistent with experimental evidence. Accept. Reason: Correct core process for CKB; redundant with the IDA/IBA annotations but not erroneous.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: Generic 'protein binding' from a high-throughput interactome screen. Uninformative as a molecular function; the biologically meaningful interactions are captured by more specific annotations. Reason: Bare protein binding does not describe a function; retained as non-core evidence of interaction only.
GO:0005515 protein binding	IPI PMID:19060904 An empirical framework for binary interactome mapping.	KEEP AS NON CORE	Summary: Generic 'protein binding' from a high-throughput binary interactome. Uninformative molecular function. Reason: Bare protein binding is not a core function; retained as non-core.
GO:0005515 protein binding	IPI PMID:19264780 Involvement of creatine kinase B in hepatitis C virus genome...	KEEP AS NON CORE	Summary: Interaction with hepatitis C virus NS4A, recruiting CKB to the viral replication complex. A genuine moonlighting interaction but represented only as generic 'protein binding'. Reason: Biologically real host-factor interaction (PMID:19264780) but a non-core, condition-specific role; the bare term is uninformative as a core function. Supporting Evidence: PMID:19264780 CKB interacts with HCV NS4A protein and forms a complex with NS3-4A, which possesses multiple enzyme activities.
GO:0005515 protein binding	IPI PMID:21145461 Dynamics of cullin-RING ubiquitin ligase network revealed by...	KEEP AS NON CORE	Summary: Generic 'protein binding' from a cullin-RING ligase network proteomic study (CUL3 association). Uninformative as a function. Reason: Bare protein binding; relates to CKB's role as a CRL substrate, retained as non-core.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Generic 'protein binding' from a high-throughput interactome map. Uninformative molecular function. Reason: Bare protein binding is not a core function; retained as non-core.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	KEEP AS NON CORE	Summary: Generic 'protein binding' from a BioPlex interactome (includes CKM and ASB9 partners). Uninformative as a standalone function. Reason: Bare protein binding; the meaningful partners (CKM dimerization, ASB9 E3 ligase) are better captured specifically. Retained as non-core.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Generic 'protein binding' from the HuRI binary interactome (ASB9). Uninformative molecular function. Reason: Bare protein binding is not a core function; retained as non-core.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: Generic 'protein binding' from a dual proteome-scale interactome (CKM, ASB9). Uninformative molecular function. Reason: Bare protein binding is not a core function; retained as non-core.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: Generic 'protein binding' from the OpenCell endogenous-tagging map. Uninformative molecular function. Reason: Bare protein binding is not a core function; retained as non-core.
GO:0005515 protein binding	IPI PMID:37207277 Using brain cell-type-specific protein interactomes to inter...	KEEP AS NON CORE	Summary: Generic 'protein binding' from a brain cell-type interactome (TCF4, CUL3). Uninformative molecular function. Reason: Bare protein binding is not a core function; retained as non-core.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: Generic 'protein binding' from a multimodal cell-map interactome (ASB9). Uninformative molecular function. Reason: Bare protein binding is not a core function; retained as non-core.
GO:0140651 futile creatine cycle	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic transfer (from mouse Q04447) of involvement in the futile creatine cycle (adipocyte thermogenesis). This role is characterized for the thermogenic-fat mitochondrial creatine cycle and has not been demonstrated for human B-CK; retain as a non-core, by-similarity possibility. Reason: The futile creatine cycle is a specialized thermogenic-fat process inferred by orthology; it is plausible but not the core energy-buffering function of cytosolic B-CK in humans.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Direct immunofluorescence (HPA) localization to the cytosol. This is the core, experimentally supported localization of B-CK. Accept. Reason: B-CK is a cytosolic enzyme; IDA from HPA directly supports the core localization.
GO:0005739 mitochondrion	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS mitochondrion localization transferred from mouse Q04447 (thermogenic-fat creatine cycle). Not the core compartment of human cytosolic B-CK. Reason: By-similarity mitochondrial localization tied to adipocyte thermogenesis; human B-CK is the cytosolic isoform and a mitochondrial pool is not directly established.
GO:0005886 plasma membrane	EXP PMID:18566107 HMSN/ACC truncation mutations disrupt brain-type creatine ki...	KEEP AS NON CORE	Summary: Experimental co-localization of CK-B with KCC3 at the plasma membrane, consistent with recruitment of B-CK to membrane ATPase microcompartments. Real but peripheral, not the core cytosolic compartment. Reason: CKB associates with the membrane via interaction with the KCC3 transporter to supply ATP locally; it is not an integral membrane protein. Retain as a non-core peripheral localization. Supporting Evidence: PMID:18566107 immunofluorescence labeling showed that CK-B co-localizes with wild-type KCC3
GO:0004111 creatine kinase activity	IDA PMID:8186255 Determination of the catalytic site of creatine kinase by si...	ACCEPT	Summary: Direct experimental evidence (site-directed mutagenesis of human B-CK) for creatine kinase activity, including identification of essential catalytic residues. The strongest support for the core molecular function. Accept. Reason: Direct assay of human CKB enzymatic activity; defines the core molecular function (EC 2.7.3.2). Supporting Evidence: PMID:8186255 The results showed residues Cys-283 and Arg-292 are essential for enzyme catalysis.
GO:0046314 phosphocreatine biosynthetic process	IDA PMID:8186255 Determination of the catalytic site of creatine kinase by si...	ACCEPT	Summary: Direct evidence for the phosphocreatine-forming (forward) direction of the creatine kinase reaction. Core process for CKB. Accept. Reason: Reflects the physiological left-to-right reaction catalyzed by CKB, directly demonstrated for the human enzyme.
GO:0004111 creatine kinase activity	ISS GO_REF:0000024	ACCEPT	Summary: ISS support (from ortholog) for the core creatine kinase activity. Consistent with direct evidence. Accept. Reason: Correct core molecular function; redundant with the experimental annotation but not erroneous.
GO:0005739 mitochondrion	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS 'is_active_in mitochondrion' transferred from mouse Q04447. Human B-CK is the cytosolic isoform; an active mitochondrial pool is not directly established. Reason: By-similarity mitochondrial activity tied to thermogenic-fat biology; not the core localization or site of activity of human cytosolic B-CK.
GO:0070062 extracellular exosome	HDA PMID:11487543 Intestinal epithelial cells secrete exosome-like vesicles.	KEEP AS NON CORE	Summary: High-throughput proteomic detection of CKB in exosomes. A real observation but reflects passive secretion/vesicle loading rather than a functional compartment. Reason: Exosome detection is common for abundant cytosolic enzymes; retain as a non-core localization, not a site of creatine kinase function.
GO:0005576 extracellular region	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS extracellular-region localization transferred from an ortholog. B-CK is a cytosolic enzyme; extracellular detection (exosomes/secretome) does not establish a functional extracellular localization. Reason: Over-propagated localization for a cytosolic enzyme; not a site of activity. Exosomal detection is better captured by the exosome annotation.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:19725078 Proteomic analysis of increased Parkin expression and its in...	KEEP AS NON CORE	Summary: CKB binds an E3 ubiquitin ligase component (Parkin/E3 interactant proteomics), consistent with CKB being a substrate of the ECS(ASB9) Cullin-RING E3 ligase that targets it for degradation. A real binding activity but reflecting CKB's role as a degradation substrate rather than a core enzyme function. Reason: Informative interaction (E3 ligase/degradation axis) but not part of CKB's core energy-metabolism function; retain as non-core.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of CKB in prostatic-secretion exosomes. Same interpretation as other exosome detections. Reason: Proteomic exosome detection; non-core localization, not a functional compartment for catalysis.
GO:0021762 substantia nigra development	HEP PMID:22926577 Quantitative proteomic analysis of human substantia nigra in...	MARK AS OVER ANNOTATED	Summary: HEP annotation derived from a disease-state differential-abundance proteomic survey of human substantia nigra. Differential expression in neurodegenerative disease does not establish a role in substantia nigra development. Reason: The supporting study compares protein abundance in disease vs control substantia nigra; it does not provide evidence that CKB is involved in the developmental process. Over-interpretation of an expression observation.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of CKB in urinary exosomes. Same interpretation as other exosome detections. Reason: Proteomic exosome detection; non-core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-200318	ACCEPT	Summary: Traceable author statement (Reactome) placing the creatine kinase reaction in the cytosol. Consistent with the core cytosolic localization. Accept. Reason: Correct core localization; the creatine kinase reaction catalyzed by CKB occurs in the cytosol.
GO:0004111 creatine kinase activity	TAS PMID:3034271 Human creatine kinase: isolation and sequence analysis of cD...	ACCEPT	Summary: Traceable author statement (original CKB cDNA cloning paper) for creatine kinase activity. Core molecular function. Accept. Reason: Correct core molecular function, supported by the foundational cloning/characterization reference.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

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