ProtNLM2 External predictions
View prediction review YAML · CDK7-protnlm-predictions-review.yaml · Review status: COMPLETE
Assessment of 2 ProtNLM GO predictions for the selected horse CDK7 protein, using mammalian experimental findings and an explicit comparison of the horse sequence.
Source documents: genes/human/CDK7/CDK7-uniprot.txt · genes/HORSE/CDK7/CDK7-bioinformatics/RESULTS.md · projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv
Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.
CNN — Correct but not novel Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: The cyclin-dependent kinase activity is supported by human CDK7 structural and biochemical work (PMID:15530371), the conserved horse catalytic Asp137 and ATP-binding residues, and 95.38% identity over the complete human reference; the horse gene is the CDK7 ortholog in PANTHER subfamily PTHR24056:SF0. The horse protein has an additional segment, but the catalytic domain is retained. The exact term is already in horse GOA, where the gene review accepts it as a core activity, so the prediction is correct but not novel. Training-set membership is unknown.
Supporting Evidence:
- file:human/CDK7/CDK7-uniprot.txt: "CC -!- FUNCTION: Serine/threonine kinase involved in cell cycle control and in CC RNA polymerase II-mediated RNA transcription (PubMed:9852112, CC PubMed:19136461, PubMed:26257281, PubMed:28768201). As a cyclin- CC dependent kinase, CDK7 is activated by the binding to cyclin-H/CCNH and CC the CDK-activating kinase assembly factor MAT1 (PubMed:41100585). CC Catalytic subunit of the CDK-activating kinase (CAK) complex, a master CC regulator of CDK activity by catalyzing the activating threonine CC phosphorylation of CDKs (PubMed:41100585). CAK activates major CC mediators of cell cycle control, including CDK1, CDK2, CDK4 and CDK6, CC and plays a key role in regulating cell cycle progression CC (PubMed:41100585). CAK complexed to the core-TFIIH basal transcription CC factor activates RNA polymerase II by serine phosphorylation of the CTD CC of POLR2A, allowing its escape from the promoter and elongation of the CC transcripts (PubMed:9852112). Initiates transcription by RNA polymerase CC II by mediating phosphorylation of POLR2A at 'Ser-5' of the repetitive CC C-terminal domain (CTD) when POLR2A is in complex with DNA, promoting CC dissociation from DNA and initiation (PubMed:19136461, PubMed:26257281, CC PubMed:28768201). Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, CC p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11 (PubMed:9372954, CC PubMed:9840937, PubMed:19136461, PubMed:26257281, PubMed:28768201, CC PubMed:41100585, PubMed:41100585). Its expression and activity are CC constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 CC activation by phosphorylation, but is inactivated in turn by p53/TP53; CC this feedback loop may lead to an arrest of the cell cycle and of the CC transcription, helping in cell recovery, or to apoptosis. Required for CC DNA-bound peptides-mediated transcription and cellular growth CC inhibition. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:11113184, CC ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:17373709, CC ECO:0000269|PubMed:17386261, ECO:0000269|PubMed:17901130, CC ECO:0000269|PubMed:19015234, ECO:0000269|PubMed:19071173, CC ECO:0000269|PubMed:19136461, ECO:0000269|PubMed:19450536, CC ECO:0000269|PubMed:19667075, ECO:0000269|PubMed:20360007, CC ECO:0000269|PubMed:26257281, ECO:0000269|PubMed:28768201, CC ECO:0000269|PubMed:41100585, ECO:0000269|PubMed:9372954, CC ECO:0000269|PubMed:9840937, ECO:0000269|PubMed:9852112}."
- file:HORSE/CDK7/CDK7-bioinformatics/RESULTS.md: "The horse sequence A0A9L0R074 (415 residues) aligns to human P50613 (346 residues) with 95.38% identity across 346 paired residues. Paired coverage is 100.0% of the human sequence and 83.37% of the horse sequence."
- PMID:15530371: "CDK7, a member of the cyclin-dependent protein kinase family, regulates the activities of other CDKs through phosphorylation on their activation segment and hence contributes to control of the eukaryotic cell cycle. CDK7 also assists in the regulation of transcription as part of the transcription factor TFIIH complex. For maximum activity and stability, CDK7 requires phosphorylation, association with cyclin H, and association with a third protein, MAT1."
COR — Correct novel prediction Review score: 2/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08
Review rationale: Human CDK7, in the cyclin H-MAT1 complex, phosphorylates CDKs, the RNA polymerase II CTD and Spt5 (PMID:16327805, chemical-genetic substrate identification), and the horse ortholog (PTHR24056:SF0) retains the catalytic domain and ATP-binding features at 95.38% identity. Protein phosphorylation is therefore a justified orthology transfer of a process the kinase itself performs. Horse GOA carries kinase MF terms but no protein phosphorylation term or descendant, and the gene review proposes none, so the BP term adds coverage; it is novel for the target annotation set, not a new biochemical discovery. Training-set membership is unknown.
Supporting Evidence:
- file:human/CDK7/CDK7-uniprot.txt: "CC -!- FUNCTION: Serine/threonine kinase involved in cell cycle control and in CC RNA polymerase II-mediated RNA transcription (PubMed:9852112, CC PubMed:19136461, PubMed:26257281, PubMed:28768201). As a cyclin- CC dependent kinase, CDK7 is activated by the binding to cyclin-H/CCNH and CC the CDK-activating kinase assembly factor MAT1 (PubMed:41100585). CC Catalytic subunit of the CDK-activating kinase (CAK) complex, a master CC regulator of CDK activity by catalyzing the activating threonine CC phosphorylation of CDKs (PubMed:41100585). CAK activates major CC mediators of cell cycle control, including CDK1, CDK2, CDK4 and CDK6, CC and plays a key role in regulating cell cycle progression CC (PubMed:41100585). CAK complexed to the core-TFIIH basal transcription CC factor activates RNA polymerase II by serine phosphorylation of the CTD CC of POLR2A, allowing its escape from the promoter and elongation of the CC transcripts (PubMed:9852112). Initiates transcription by RNA polymerase CC II by mediating phosphorylation of POLR2A at 'Ser-5' of the repetitive CC C-terminal domain (CTD) when POLR2A is in complex with DNA, promoting CC dissociation from DNA and initiation (PubMed:19136461, PubMed:26257281, CC PubMed:28768201). Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, CC p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11 (PubMed:9372954, CC PubMed:9840937, PubMed:19136461, PubMed:26257281, PubMed:28768201, CC PubMed:41100585, PubMed:41100585). Its expression and activity are CC constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 CC activation by phosphorylation, but is inactivated in turn by p53/TP53; CC this feedback loop may lead to an arrest of the cell cycle and of the CC transcription, helping in cell recovery, or to apoptosis. Required for CC DNA-bound peptides-mediated transcription and cellular growth CC inhibition. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:11113184, CC ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:17373709, CC ECO:0000269|PubMed:17386261, ECO:0000269|PubMed:17901130, CC ECO:0000269|PubMed:19015234, ECO:0000269|PubMed:19071173, CC ECO:0000269|PubMed:19136461, ECO:0000269|PubMed:19450536, CC ECO:0000269|PubMed:19667075, ECO:0000269|PubMed:20360007, CC ECO:0000269|PubMed:26257281, ECO:0000269|PubMed:28768201, CC ECO:0000269|PubMed:41100585, ECO:0000269|PubMed:9372954, CC ECO:0000269|PubMed:9840937, ECO:0000269|PubMed:9852112}."
- file:HORSE/CDK7/CDK7-bioinformatics/RESULTS.md: "The horse sequence A0A9L0R074 (415 residues) aligns to human P50613 (346 residues) with 95.38% identity across 346 paired residues. Paired coverage is 100.0% of the human sequence and 83.37% of the horse sequence."
- PMID:15530371: "CDK7, a member of the cyclin-dependent protein kinase family, regulates the activities of other CDKs through phosphorylation on their activation segment and hence contributes to control of the eukaryotic cell cycle. CDK7 also assists in the regulation of transcription as part of the transcription factor TFIIH complex. For maximum activity and stability, CDK7 requires phosphorylation, association with cyclin H, and association with a third protein, MAT1."
- PMID:16327805: "Cdk7-AS-cyclin H-Mat1 phosphorylates approximately 10-15 endogenous polypeptides in nuclear extracts. We identify seven of these as known and previously unknown Cdk7 substrates"