CIA Targeting Complex transfers 4Fe-4S cluster to apoproteins

Stable Identifier
R-HSA-2564828
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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CIA Targeting Complex transfers 4Fe-4S cluster to apoproteins
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A complex of four proteins termed CIA targeting complex is involved in the delivery of the NUBP1-NUBP2-bound Fe/S cluster to specific target apoproteins. NARFL (IOP1, Nar1 in yeast) is similar in sequence to iron-only hydrogenases and binds two [4Fe-4S] clusters. These cofactors are essential for biogenesis but their molecular function is unknown. The WD40 domain protein CIAO1 (Cia1 in yeast) forms a propeller-like structure which may serve as a docking site for the other members of the CIA targeting complex. The role of FAM96B (YHR122W, CIA2 in yeast) and MMS19 is still unclear, but they show some specificity for the delivery of Fe/S clusters into certain target apoproteins. They directly interact with numerous Fe/S target proteins including many proteins involved in nuclear DNA integrity and maintenance such as DNA polymerases (POLD1), helicases of the DNA repair pathway (XPD or FANCJ) or of telomere maintenance (RTEL1), and primases. Cells with mutated MMS19 are hypersensitive to DNA damage and have elongated telomeres therefore these target proteins are relevant to various cancer-related diseases and aging.
Literature References
PubMed ID Title Journal Year
22678362 MMS19 assembles iron-sulfur proteins required for DNA metabolism and genomic integrity

Netz, DJ, Pierik, AJ, Lill, R, Sharma, T, Vashisht, AA, Stehling, O, Mascarenhas, J, Wohlschlegel, JA, Jonsson, ZO

Science 2012
22678361 MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism

Flynn, H, Boulton, SJ, León Ortiz, AM, Gari, K, Skehel, JM, Borel, V

Science 2012
23150669 The Mammalian Proteins MMS19, MIP18, and ANT2 Are Involved in Cytoplasmic Iron-Sulfur Cluster Protein Assembly

Uringa, EJ, Lansdorp, PM, van Wietmarschen, N, Moradian, A, Morin, GB

J. Biol. Chem. 2012
Participants
Input
Output
Participates
as an event of
Catalyst Activity

iron-sulfur transferase activity of NARFL:CIAO1:FAM96B:MMS19 [cytosol]

Physical Entity
NARFL:CIAO1:FAM96B:MMS19 [cytosol] (Homo sapiens)
Activity
iron-sulfur transferase activity (GO:0036455)
Inferred From
CIA Targeting Complex transfers 4Fe-4S clusters to apoproteins (Saccharomyces cerevisiae)
Authored
Lill, R  (2012-11-07)
Reviewed
Uringa, EJ  (2013-02-05)
Created
May, B  (2012-11-08)
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