Ckmt2 encodes rat mitochondrial creatine kinase S-type, a mitochondrial phosphotransferase that reversibly transfers phosphate between ATP and creatine to support phosphocreatine-based energy buffering in tissues with high energy demand. The review accepts creatine kinase activity and phosphocreatine biosynthesis as core and marks broad kinase/transferase and developmental expression annotations as non-core or over-annotated.
| 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 GO; GO:0004111; F:creatine kinase activity; IBA:GO_Central. 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 GO; GO:0005739; C:mitochondrion; IBA:GO_Central. 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 GO; GO:0046314; P:phosphocreatine biosynthetic process; IBA:GO_Central. 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 GO; GO:0004111; F:creatine kinase activity; IBA:GO_Central. 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 GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell. 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: UniProtKB:P09605 GO; GO:0007519; P:skeletal muscle tissue development; IEP:RGD. |
| 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 GO; GO:0046314; P:phosphocreatine biosynthetic process; IEA:InterPro (InterPro:IPR000749). |
| 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 GO; GO:1901612; F:cardiolipin binding; IDA:RGD. |
| 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 GO; GO:0007507; P:heart development; IEP:RGD. 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 GO; GO:0007519; P:skeletal muscle tissue development; IEP:RGD. 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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