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Overview

Uniprot IDQ91WS0
Protein NameCDGSH iron-sulfur domain-containing protein 1
Gene NameCisd1
OrganismMus musculus

Kla Sites from experimental identification

Position Flanking peptide
104 NVGPLIIKKKET***
37 AYKKFYAKENRTKAM
55 QIQKDNPKVVHAFDM
68 DMEDLGDKAVYCRCW

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 (By similarity). 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 (By similarity). Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation (PubMed:17376863). 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 (By similarity)

Protein Sequence

10 MGLSSNSAVR 20 VEWIAAVTFA 30 AGTAALGYLA 40 YKKFYAKENR 50 TKAMVNLQIQ 60 KDNPKVVHAF 70 DMEDLGDKAV 80 YCRCWRSKKF 90 PFCDGAHIKH 100 NEETGDNVGP LIIKKKET

Gene Ontology

Classification GO ID Description
Cellular Component GO:0032473 cytoplasmic side of mitochondrial outer membrane
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:0005506 iron ion binding
Molecular Function GO:0047801 L-cysteine transaminase activity
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
Biological Process GO:0043457 regulation of cellular respiration

Reference

[1] Zhuo W, Zhang M, Tan J, Gao Y, Wang Y et al.. Lysine lactylation analysis of proteins in the heart of the Kawasaki disease mouse model.. Front Cell Dev Biol 13:1550220. 2025. PMID: 40114965.

[2] Wu D, Tang Y, Li X, Xiong S, Zhang Z et al.. Characterization of protein lactylation in healthy and ischemic mouse hearts.. Front Cardiovasc Med 12:1644886. 2025. PMID: 41089239.