Ckmt2 encodes the sarcomeric mitochondrial creatine kinase (sMtCK, creatine kinase S-type), expressed in heart and skeletal muscle. It is a phosphotransferase of the ATP:guanido phosphotransferase family that reversibly transfers the gamma-phosphate of ATP to creatine, generating phosphocreatine. Four homodimers assemble into an octamer that sits on the intermembrane-space face of the mitochondrial inner membrane, bound to cardiolipin and associated with VDAC and ANT at contact sites. There it converts newly exported mitochondrial ATP into diffusible phosphocreatine, which carries high-energy phosphate to cytosolic ATPases (the creatine kinase/phosphocreatine shuttle). Its mRNA rises sharply after birth in heart and skeletal muscle, in step with their increasing oxidative energy demand.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004111 creatine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Ckmt2 is a mitochondrial creatine kinase S-type; the creatine kinase activity annotation is supported by the fetched UniProt/GOA evidence (IBA, GO_REF:0000033) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ckmt2 core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:P09605 Reaction=creatine + ATP = N-phosphocreatine + ADP + H(+); file:rat/Ckmt2/Ckmt2-deep-research-falcon.md CKMT2 is a **phosphotransferase** transferring the Ξ³-phosphoryl group of ATP to creatine. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: The mitochondrion annotation is plausible for Ckmt2 but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Ckmt2. Supporting Evidence: UniProtKB:P09605 SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side. file:rat/Ckmt2/Ckmt2-deep-research-falcon.md Mitochondrial CK is localized to the **mitochondrial intermembrane and cristae space** and assembles into **cuboidal homooctamers** that are peripherally membrane-associated. |
| GO:0046314 phosphocreatine biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Ckmt2 is a mitochondrial creatine kinase S-type; the phosphocreatine biosynthetic process annotation is supported by the fetched UniProt/GOA evidence (IBA, GO_REF:0000033) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ckmt2 core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:P09605 Reaction=creatine + ATP = N-phosphocreatine + ADP + H(+); file:rat/Ckmt2/Ckmt2-deep-research-falcon.md In heart, CKMT2 is positioned to convert mitochondrial ATP into PCr, which diffuses to ATPases |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: The catalytic activity annotation is related to Ckmt2 function, but it is too generic compared with the supported specific term(s): creatine kinase activity. Reason: The annotation is directionally related to Ckmt2 but is too broad; the specific catalytic activity is more informative. Proposed replacements: creatine kinase activity Supporting Evidence: UniProtKB:P09605 FUNCTION: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. |
| GO:0004111 creatine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Ckmt2 is a mitochondrial creatine kinase S-type; the creatine kinase activity annotation is supported by the fetched UniProt/GOA evidence (IEA, GO_REF:0000120) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ckmt2 core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:P09605 Reaction=creatine + ATP = N-phosphocreatine + ADP + H(+); file:rat/Ckmt2/Ckmt2-deep-research-falcon.md CKMT2 is a **phosphotransferase** transferring the Ξ³-phosphoryl group of ATP to creatine. |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The mitochondrial inner membrane annotation is plausible for Ckmt2 but should be kept as non-core context rather than used to define the gene product function. Reason: The localization is useful context but is not the core molecular function of Ckmt2. Supporting Evidence: UniProtKB:P09605 SUBCELLULAR LOCATION: Mitochondrion inner membrane; Peripheral membrane protein; Intermembrane side. file:rat/Ckmt2/Ckmt2-deep-research-falcon.md Mitochondrial CK is localized to the **mitochondrial intermembrane and cristae space** and assembles into **cuboidal homooctamers** that are peripherally membrane-associated. |
| GO:0007519 skeletal muscle tissue development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: The skeletal muscle tissue development annotation likely reflects indirect phenotype, expression, or pathway context rather than the direct conserved function of Ckmt2. Reason: This term derives from the developmental mRNA expression pattern (sMtCK mRNA is markedly upregulated postnatally in skeletal muscle, PMID:8086475), which reflects the rising metabolic demand for phosphocreatine buffering as muscle matures rather than a direct instructive role of Ckmt2 in tissue development. Supporting Evidence: PMID:8086475 sMtCK mRNA in skeletal muscle is also extremely low prenatally but is markedly upregulated at birth and doubles by 28 d postnatally. |
| GO:0016301 kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: The kinase activity annotation is related to Ckmt2 function, but it is too generic compared with the supported specific term(s): creatine kinase activity. Reason: The annotation is directionally related to Ckmt2 but is too broad; the specific catalytic activity is more informative. Proposed replacements: creatine kinase activity Supporting Evidence: UniProtKB:P09605 FUNCTION: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | IEA GO_REF:0000002 | MODIFY | Summary: The transferase activity, transferring phosphorus-containing groups annotation is related to Ckmt2 function, but it is too generic compared with the supported specific term(s): creatine kinase activity. Reason: The annotation is directionally related to Ckmt2 but is too broad; the specific catalytic activity is more informative. Proposed replacements: creatine kinase activity Supporting Evidence: UniProtKB:P09605 FUNCTION: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. |
| GO:0016775 phosphotransferase activity, nitrogenous group as acceptor | IEA GO_REF:0000002 | MODIFY | Summary: The phosphotransferase activity, nitrogenous group as acceptor annotation is related to Ckmt2 function, but it is too generic compared with the supported specific term(s): creatine kinase activity. Reason: The annotation is directionally related to Ckmt2 but is too broad; the specific catalytic activity is more informative. Proposed replacements: creatine kinase activity Supporting Evidence: UniProtKB:P09605 FUNCTION: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa. |
| GO:0046314 phosphocreatine biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: Ckmt2 is a mitochondrial creatine kinase S-type; the phosphocreatine biosynthetic process annotation is supported by the fetched UniProt/GOA evidence (IEA, GO_REF:0000002) and represents a core or direct activity/process. Reason: This term captures a directly supported part of Ckmt2 core biochemistry or the closest GO process for that activity. Supporting Evidence: UniProtKB:P09605 Reaction=creatine + ATP = N-phosphocreatine + ADP + H(+); file:rat/Ckmt2/Ckmt2-deep-research-falcon.md In heart, CKMT2 is positioned to convert mitochondrial ATP into PCr, which diffuses to ATPases |
| GO:1901612 cardiolipin binding | IDA PMID:3972849 Cardiolipin is the membrane receptor for mitochondrial creat... | KEEP AS NON CORE | Summary: The cardiolipin binding annotation is plausible for Ckmt2 but should be kept as non-core context rather than used to define the gene product function. Reason: This is plausible biochemical context for Ckmt2, but it is not the defining evolved activity. Supporting Evidence: UniProtKB:P09605 MISCELLANEOUS: Mitochondrial creatine kinase binds cardiolipin. PMID:3972849 mt-CK was bound by liposomes but only if they contained cardiolipin. |
| GO:0007507 heart development | IEP PMID:8086475 Developmental expression of sarcomeric and ubiquitous mitoch... | MARK AS OVER ANNOTATED | Summary: The heart development annotation likely reflects indirect phenotype, expression, or pathway context rather than the direct conserved function of Ckmt2. Reason: This IEP term derives from the developmental mRNA expression pattern reported in PMID:8086475, where sMtCK mRNA in heart is undetectable prenatally but dramatically upregulated postnatally. This pattern reflects the maturing heart's increasing metabolic demand for phosphocreatine buffering, not a direct instructive role of Ckmt2 in heart morphogenesis. Supporting Evidence: UniProtKB:P09605 TISSUE SPECIFICITY: Sarcomere-specific. Found only in heart and skeletal muscles. PMID:8086475 sMtCK mRNA in heart is undetectable prenatally but is dramatically upregulated by 28 d postnatally. |
| GO:0007519 skeletal muscle tissue development | IEP PMID:8086475 Developmental expression of sarcomeric and ubiquitous mitoch... | MARK AS OVER ANNOTATED | Summary: The skeletal muscle tissue development annotation likely reflects indirect phenotype, expression, or pathway context rather than the direct conserved function of Ckmt2. Reason: This IEP term derives from the developmental mRNA expression pattern reported in PMID:8086475, where sMtCK mRNA in skeletal muscle is extremely low prenatally but markedly upregulated at birth and doubles by 28 d postnatally. This reflects the maturing muscle's rising demand for phosphocreatine buffering, not a direct instructive role of Ckmt2 in tissue development. Supporting Evidence: UniProtKB:P09605 TISSUE SPECIFICITY: Sarcomere-specific. Found only in heart and skeletal muscles. PMID:8086475 sMtCK mRNA in skeletal muscle is also extremely low prenatally but is markedly upregulated at birth and doubles by 28 d postnatally. |
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