ISCU [The Human Chemical-Genetic Interaction Map Project]

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======= ISCU =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: ISCU
  * **<color #00a2e8>Official Name</color>**: iron-sulfur cluster assembly enzyme
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=23479|23479]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9H1K1|Q9H1K1]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=ISCU&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ISCU|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/611911|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a component of the iron-sulfur (Fe-S) cluster scaffold. Fe-S clusters are cofactors that play a role in the function of a diverse set of enzymes, including those that regulate metabolism, iron homeostasis, and oxidative stress response. Alternative splicing results in transcript variants encoding different protein isoforms that localize either to the cytosol or to the mitochondrion. Mutations in this gene have been found in patients with hereditary myopathy with lactic acidosis. A disease-associated mutation in an intron may activate a cryptic splice site, resulting in the production of a splice variant encoding a putatively non-functional protein. A pseudogene of this gene is present on chromosome 1. [provided by RefSeq, Feb 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Scaffold protein for the de novo synthesis of iron- sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins (PubMed:11060020). First, a [2Fe-2S] cluster is transiently assembled on the scaffold protein ISCU. In a second step, the cluster is released from ISCU, transferred to a glutaredoxin GLRX5, followed by the formation of mitochondrial [2Fe-2S] proteins, the synthesis of [4Fe-4S] clusters and their target-specific insertion into the recipient apoproteins. Cluster assembly on ISCU depends on the function of the cysteine desulfurase complex NFS1-LYRM4/ISD11, which serves as the sulfur donor for cluster synthesis, the iron-binding protein frataxin as the putative iron donor, and the electron transfer chain comprised of ferredoxin reductase and ferredoxin, which receive their electrons from NADH (By similarity). {ECO:0000250|UniProtKB:Q03020, ECO:0000269|PubMed:11060020}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|NifU N|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of iron ion import across plasma membrane|
|regulation of iron ion import across plasma membrane|
|negative regulation of iron ion transmembrane transport|
|positive regulation of mitochondrial electron transport, NADH to ubiquinone|
|negative regulation of iron ion transport|
|positive regulation of aconitate hydratase activity|
|regulation of aconitate hydratase activity|
|regulation of iron ion transmembrane transport|
|positive regulation of mitochondrial ATP synthesis coupled electron transport|
|regulation of mitochondrial electron transport, NADH to ubiquinone|
|regulation of mitochondrial ATP synthesis coupled electron transport|
|regulation of iron ion transport|
|positive regulation of cellular respiration|
|positive regulation of oxidative phosphorylation|
|metallo-sulfur cluster assembly|
|iron-sulfur cluster assembly|
|2 iron, 2 sulfur cluster binding|
|positive regulation of lyase activity|
|ferrous iron binding|
|regulation of oxidative phosphorylation|
|regulation of cellular respiration|
|4 iron, 4 sulfur cluster binding|
|regulation of lyase activity|
|positive regulation of ATP metabolic process|
|molecular adaptor activity|
|cellular iron ion homeostasis|
|iron ion homeostasis|
|negative regulation of cation transmembrane transport|
|negative regulation of ion transmembrane transport|
|cellular transition metal ion homeostasis|
|negative regulation of transmembrane transport|
|regulation of ATP metabolic process|
|transition metal ion homeostasis|
|iron ion binding|
|negative regulation of ion transport|
|regulation of generation of precursor metabolites and energy|
|cofactor biosynthetic process|
|regulation of cation transmembrane transport|
|sulfur compound metabolic process|
|mitochondrial matrix|
|regulation of metal ion transport|
|cofactor metabolic process|
|regulation of ion transmembrane transport|
|negative regulation of transport|
|cellular metal ion homeostasis|
|regulation of transmembrane transport|
|metal ion homeostasis|
|cellular cation homeostasis|
|cellular ion homeostasis|
|regulation of ion transport|
|cation homeostasis|
|inorganic ion homeostasis|
|cellular chemical homeostasis|
|ion homeostasis|
|cellular homeostasis|
|regulation of cellular localization|
|positive regulation of phosphorylation|
|chemical homeostasis|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|mitochondrion|
|positive regulation of catalytic activity|
|regulation of phosphorylation|
|homeostatic process|
|small molecule metabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp435|JQ1 0.8μM R08 exp435]]|-2.67|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|-2.43|
|[[:results:exp532|TIC10 10μM R08 exp532]]|-2.05|
|[[:results:exp256|HMS-I1 10μM R06 exp256]]|-1.91|
|[[:results:exp64|Nocodazole 0.2μM R02 exp64]]|-1.88|
|[[:results:exp392|PT-1 25μM R07 exp392]]|1.7|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|1.72|
|[[:results:exp185|L-BMAA 500 to 750μM on day4 R04 exp185]]|1.74|
|[[:results:exp1|5-Fluorouracil 2μM R00 exp1]]|1.75|
|[[:results:exp300|VE-822 0.04μM R06 exp300]]|1.8|
|[[:results:exp235|Geldanamycin 0.01μM R05 exp235]]|1.83|
|[[:results:exp125|GSK461364A 0.005μM R03 exp125]]|1.85|
|[[:results:exp418|Tunicamycin 0.04μM R07 exp418]]|1.86|
|[[:results:exp301|VER-155008 3.9μM R06 exp301]]|1.87|
|[[:results:exp37|Wortmannin 0.5μM R00 exp37]]|1.88|
|[[:results:exp340|BN82002 4μM R07 exp340]]|1.97|
|[[:results:exp5|Alpha-Amanitin 0.5μM R00 exp5]]|1.99|
|[[:results:exp114|A-196 10μM R03 exp114]]|2.11|
|[[:results:exp222|Betulinic acid 10 to 15μM on day4 R05 exp222]]|2.25|
|[[:results:exp238|Parthenolide 2.5μM R05 exp238]]|2.29|
|[[:results:exp140|Nicotinate 1000μM R03 exp140]]|2.49|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:psmb4|PSMB4]]|0.555|
|[[:human genes:n:napa|NAPA]]|0.544|
|[[:human genes:t:tceb3cl2|TCEB3CL2]]|0.544|
|[[:human genes:n:nupl1|NUPL1]]|0.537|
|[[:human genes:p:polr2j3|POLR2J3]]|0.524|
|[[:human genes:p:psma6|PSMA6]]|0.518|
|[[:human genes:e:eif4a3|EIF4A3]]|0.512|
|[[:human genes:r:rbm39|RBM39]]|0.511|
|[[:human genes:t:tceb3c|TCEB3C]]|0.504|
|[[:human genes:s:supt5h|SUPT5H]]|0.5|
|[[:human genes:o:orc1|ORC1]]|0.485|
|[[:human genes:s:sf3a1|SF3A1]]|0.483|
|[[:human genes:t:tfip11|TFIP11]]|0.481|
|[[:human genes:r:rbbp5|RBBP5]]|0.476|
|[[:human genes:d:dnm2|DNM2]]|0.476|
|[[:human genes:v:vasn|VASN]]|0.475|
|[[:human genes:p:psmd11|PSMD11]]|0.471|
|[[:human genes:c:cactin|CACTIN]]|0.47|
|[[:human genes:t:tceb3cl|TCEB3CL]]|0.469|
|[[:human genes:a:akirin2|AKIRIN2]]|0.466|
|[[:human genes:p:pola1|POLA1]]|0.465|
|[[:human genes:s:snrpa1|SNRPA1]]|0.465|
|[[:human genes:r:rps12|RPS12]]|0.463|
|[[:human genes:r:rps5|RPS5]]|0.462|
|[[:human genes:e:exosc5|EXOSC5]]|0.458|
|[[:human genes:p:pole2|POLE2]]|0.458|
|[[:human genes:t:tbc1d3h|TBC1D3H]]|0.456|
|[[:human genes:g:gga3|GGA3]]|0.454|
|[[:human genes:s:setd1a|SETD1A]]|0.454|
|[[:human genes:r:rpl35|RPL35]]|0.453|
|[[:human genes:p:paf1|PAF1]]|0.452|
|[[:human genes:z:znf148|ZNF148]]|0.452|
|[[:human genes:r:rps28|RPS28]]|0.451|
|[[:human genes:s:supt6h|SUPT6H]]|0.451|
|[[:human genes:n:nup155|NUP155]]|0.451|
|[[:human genes:p:psmc2|PSMC2]]|0.45|
|[[:human genes:p:pole|POLE]]|0.45|
|[[:human genes:t:ticrr|TICRR]]|0.449|
|[[:human genes:r:rps2|RPS2]]|0.449|
|[[:human genes:f:fam25b|FAM25B]]|0.447|
|[[:human genes:c:chd4|CHD4]]|0.446|
|[[:human genes:c:cdc45|CDC45]]|0.445|
|[[:human genes:s:stil|STIL]]|0.445|
|[[:human genes:a:aqr|AQR]]|0.445|
|[[:human genes:a:atp6v1c1|ATP6V1C1]]|0.445|
|[[:human genes:r:rnf113a|RNF113A]]|0.444|
|[[:human genes:a:atp6v0c|ATP6V0C]]|0.443|
|[[:human genes:c:ccna2|CCNA2]]|0.443|
|[[:human genes:p:psmd1|PSMD1]]|0.443|
|[[:human genes:d:ddtl|DDTL]]|0.443|
|[[:human genes:n:nufip2|NUFIP2]]|0.442|
|[[:human genes:e:exosc6|EXOSC6]]|0.441|
|[[:human genes:o:orc6|ORC6]]|0.44|
|[[:human genes:p:psap|PSAP]]|0.44|
|[[:human genes:k:krt78|KRT78]]|0.439|
|[[:human genes:n:nup160|NUP160]]|0.439|
|[[:human genes:g:golga8o|GOLGA8O]]|0.437|
|[[:human genes:c:copg1|COPG1]]|0.437|
|[[:human genes:c:cwc22|CWC22]]|0.437|
|[[:human genes:c:chaf1a|CHAF1A]]|0.436|
|[[:human genes:c:cnpy3|CNPY3]]|0.433|
|[[:human genes:p:psmb3|PSMB3]]|0.433|
|[[:human genes:t:tuba8|TUBA8]]|0.433|
|[[:human genes:m:mt1e|MT1E]]|0.433|
|[[:human genes:s:sart1|SART1]]|0.432|
|[[:human genes:p:psmd14|PSMD14]]|0.432|
|[[:human genes:z:zfand5|ZFAND5]]|0.431|
|[[:human genes:a:arcn1|ARCN1]]|0.431|
|[[:human genes:c:cbwd5|CBWD5]]|0.43|
|[[:human genes:t:terf2|TERF2]]|0.429|
|[[:human genes:e:egr2|EGR2]]|0.428|
|[[:human genes:c:cgb2|CGB2]]|0.426|
|[[:human genes:p:plk4|PLK4]]|0.425|
|[[:human genes:p:plk1|PLK1]]|0.425|
|[[:human genes:h:hnrnpa1|HNRNPA1]]|0.424|
|[[:human genes:n:nbpf16|NBPF16]]|0.424|
|[[:human genes:x:xylt2|XYLT2]]|0.424|
|[[:human genes:k:kctd17|KCTD17]]|0.424|
|[[:human genes:o:or10g3|OR10G3]]|0.424|
|[[:human genes:a:atp6v1a|ATP6V1A]]|0.423|
|[[:human genes:t:tbc1d3l|TBC1D3L]]|0.423|
|[[:human genes:p:psmc1|PSMC1]]|0.423|
|[[:human genes:a:acsf2|ACSF2]]|0.423|
|[[:human genes:c:cdc73|CDC73]]|0.423|
|[[:human genes:t:tbc1d3e|TBC1D3E]]|0.422|
|[[:human genes:c:cope|COPE]]|0.422|
|[[:human genes:g:golga6l3|GOLGA6L3]]|0.422|
|[[:human genes:n:nup205|NUP205]]|0.422|
|[[:human genes:t:tbc1d3k|TBC1D3K]]|0.422|
|[[:human genes:g:golga8j|GOLGA8J]]|0.421|
|[[:human genes:a:ankle2|ANKLE2]]|0.421|
|[[:human genes:u:utp20|UTP20]]|0.421|
|[[:human genes:c:c14orf93|C14orf93]]|0.421|
|[[:human genes:t:tbc1d3i|TBC1D3I]]|0.421|
|[[:human genes:r:rnf4|RNF4]]|0.421|
|[[:human genes:p:psmd3|PSMD3]]|0.42|
|[[:human genes:p:pcf11|PCF11]]|0.419|
|[[:human genes:s:srsf1|SRSF1]]|0.419|
|[[:human genes:c:cbwd3|CBWD3]]|0.419|
|[[:human genes:t:top1mt|TOP1MT]]|0.419|
|[[:human genes:c:casc3|CASC3]]|0.418|
|[[:human genes:r:rps19bp1|RPS19BP1]]|0.418|
|[[:human genes:s:syt9|SYT9]]|0.418|
|[[:human genes:p:pola2|POLA2]]|0.417|
|[[:human genes:t:tgfbrap1|TGFBRAP1]]|0.417|
|[[:human genes:t:traip|TRAIP]]|0.417|
|[[:human genes:c:cdrt15|CDRT15]]|0.416|
|[[:human genes:r:rps19|RPS19]]|0.416|
|[[:human genes:r:riok2|RIOK2]]|0.416|
|[[:human genes:s:ssh2|SSH2]]|0.415|
|[[:human genes:t:tbc1d3g|TBC1D3G]]|0.415|
|[[:human genes:x:xab2|XAB2]]|0.414|
|[[:human genes:t:tbc1d3f|TBC1D3F]]|0.414|
|[[:human genes:f:fancm|FANCM]]|0.413|
|[[:human genes:g:gar1|GAR1]]|0.413|
|[[:human genes:k:kif3c|KIF3C]]|0.413|
|[[:human genes:c:cdc6|CDC6]]|0.412|
|[[:human genes:p:polr2f|POLR2F]]|0.411|
|[[:human genes:c:crnkl1|CRNKL1]]|0.411|
|[[:human genes:d:dido1|DIDO1]]|0.411|
|[[:human genes:b:brd2|BRD2]]|0.41|
|[[:human genes:c:cox8a|COX8A]]|0.409|
|[[:human genes:s:sf3b2|SF3B2]]|0.409|
|[[:human genes:n:nop16|NOP16]]|0.409|
|[[:human genes:i:ints6|INTS6]]|0.408|
|[[:human genes:c:cyb561a3|CYB561A3]]|0.408|
|[[:human genes:s:snrnp70|SNRNP70]]|0.408|
|[[:human genes:c:clpx|CLPX]]|0.407|
|[[:human genes:p:pde4dip|PDE4DIP]]|0.407|
|[[:human genes:p:psmb1|PSMB1]]|0.407|
|[[:human genes:n:npipb5|NPIPB5]]|0.407|
|[[:human genes:h:hist1h2be|HIST1H2BE]]|0.407|
|[[:human genes:c:cbwd6|CBWD6]]|0.406|
|[[:human genes:m:mylk3|MYLK3]]|0.405|
|[[:human genes:s:sf3a2|SF3A2]]|0.405|
|[[:human genes:r:rad21|RAD21]]|0.404|
|[[:human genes:f:fbxo5|FBXO5]]|0.404|
|[[:human genes:s:sf3a3|SF3A3]]|0.404|
|[[:human genes:r:rrp7a|RRP7A]]|0.403|
|[[:human genes:r:rpl30|RPL30]]|0.403|
|[[:human genes:g:gprin2|GPRIN2]]|0.401|
|[[:human genes:p:pan3|PAN3]]|0.401|
|[[:human genes:r:rps14|RPS14]]|0.4|
|[[:human genes:u:ube2q2l|UBE2Q2L]]|0.4|
|[[:human genes:r:rps9|RPS9]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 732/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|28/28|
|blood|28/28|
|bone|26/26|
|breast|33/33|
|central nervous system|56/56|
|cervix|4/4|
|colorectal|16/17|
|esophagus|13/13|
|fibroblast|1/1|
|gastric|16/16|
|kidney|21/21|
|liver|20/20|
|lung|75/75|
|lymphocyte|16/16|
|ovary|25/26|
|pancreas|24/24|
|peripheral nervous system|15/16|
|plasma cell|15/15|
|prostate|1/1|
|skin|24/24|
|soft tissue|9/9|
|thyroid|2/2|
|upper aerodigestive|22/22|
|urinary tract|27/29|
|uterus|5/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 121
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.05 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='ISCU Expression in NALM6 Cells: 6.05'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>