Search Results
Overview
| Uniprot ID | Q9NZ45 |
|---|---|
| Protein Name | CDGSH iron-sulfur domain-containing protein 1 |
| Gene Name | CISD1 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 104 | NVGPLIIKKKET*** |
| 37 | AYKRFYVKDHRNKAM |
| 42 | YVKDHRNKAMINLHI |
| 51 | MINLHIQKDNPKIVH |
| 55 | HIQKDNPKIVHAFDM |
| 68 | DMEDLGDKAVYCRCW |
| 79 | CRCWRSKKFPFCDGA |
| 89 | FCDGAHTKHNEETGD |
Function
L-cysteine transaminase that catalyzes the reversible transfer of the amino group from L-cysteine to the alpha-keto acid 2-oxoglutarate to respectively form 2-oxo-3-sulfanylpropanoate and L-glutamate (PubMed:36194135). The catalytic cycle occurs in the presence of pyridoxal 5'-phosphate (PLP) cofactor that facilitates transamination by initially forming an internal aldimine with the epsilon-amino group of active site Lys-55 residue on the enzyme (PLP-enzyme aldimine), subsequently displaced by formation of an external aldimine with the substrate amino group (PLP-L-cysteine aldimine). The external aldimine is further deprotonated to form a carbanion intermediate, which in the presence of 2-oxoglutarate regenerates PLP yielding final products 2-oxo-3-sulfanylpropanoate and L-glutamate. The proton transfer in carbanion intermediate is suggested to be controlled by the active site lysine residue, whereas PLP stabilizes carbanion structure through electron delocalization, also known as the electron sink effect (PubMed:36194135). Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation (By similarity). May be involved in iron-sulfur cluster shuttling and/or in redox reactions. Can transfer the [2Fe-2S] cluster to an apo-acceptor protein only when in the oxidation state, likely serving as a redox sensor that regulates mitochondrial iron-sulfur cluster assembly and iron trafficking upon oxidative stress (PubMed:17584744, PubMed:21788481, PubMed:23758282)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005741 | mitochondrial outer membrane |
| Cellular Component | GO:0005739 | mitochondrion |
| Molecular Function | GO:0051537 | 2 iron, 2 sulfur cluster binding |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0047801 | L-cysteine transaminase activity |
| Molecular Function | GO:0046872 | metal ion binding |
| Molecular Function | GO:0042803 | protein homodimerization activity |
| Molecular Function | GO:0030170 | pyridoxal phosphate binding |
| Biological Process | GO:0006879 | intracellular iron ion homeostasis |
| Biological Process | GO:0051604 | protein maturation |
| Biological Process | GO:0010506 | regulation of autophagy |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[4] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.
[5] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[6] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.