ALAD [The Human Chemical-Genetic Interaction Map Project]

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======= ALAD =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: ALAD
  * **<color #00a2e8>Official Name</color>**: aminolevulinate dehydratase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=210|210]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P13716|P13716]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=ALAD&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ALAD|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/125270|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The ALAD enzyme is composed of 8 identical subunits and catalyzes the condensation of 2 molecules of delta-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). ALAD catalyzes the second step in the porphyrin and heme biosynthetic pathway; zinc is essential for enzymatic activity. ALAD enzymatic activity is inhibited by lead and a defect in the ALAD structural gene can cause increased sensitivity to lead poisoning and acute hepatic porphyria. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen. {ECO:0000269|PubMed:11032836, ECO:0000269|PubMed:19812033}.

<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'>
|ALAD|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|porphobilinogen synthase activity|
|response to platinum ion|
|proteasome core complex binding|
|response to vitamin B1|
|response to aluminum ion|
|cellular response to lead ion|
|response to methylmercury|
|protoporphyrinogen IX biosynthetic process|
|response to cobalt ion|
|protoporphyrinogen IX metabolic process|
|response to selenium ion|
|response to mercury ion|
|response to vitamin E|
|response to herbicide|
|heme biosynthetic process|
|response to lead ion|
|porphyrin-containing compound biosynthetic process|
|cellular response to interleukin-4|
|tetrapyrrole biosynthetic process|
|response to interleukin-4|
|heme metabolic process|
|response to arsenic-containing substance|
|response to iron ion|
|porphyrin-containing compound metabolic process|
|catalytic activity|
|pigment biosynthetic process|
|response to zinc ion|
|negative regulation of proteasomal protein catabolic process|
|tetrapyrrole metabolic process|
|response to cadmium ion|
|pigment metabolic process|
|response to activity|
|negative regulation of proteolysis involved in cellular protein catabolic process|
|response to fatty acid|
|response to vitamin|
|negative regulation of cellular protein catabolic process|
|response to amino acid|
|secretory granule lumen|
|ficolin-1-rich granule lumen|
|response to ethanol|
|negative regulation of protein catabolic process|
|response to glucocorticoid|
|response to ionizing radiation|
|response to corticosteroid|
|regulation of proteasomal protein catabolic process|
|cellular response to metal ion|
|cofactor biosynthetic process|
|response to nutrient|
|regulation of proteolysis involved in cellular protein catabolic process|
|cellular response to inorganic substance|
|response to alcohol|
|regulation of cellular protein catabolic process|
|negative regulation of cellular catabolic process|
|response to antibiotic|
|negative regulation of catabolic process|
|response to lipopolysaccharide|
|response to molecule of bacterial origin|
|response to steroid hormone|
|protein homooligomerization|
|response to hypoxia|
|response to acid chemical|
|negative regulation of proteolysis|
|response to decreased oxygen levels|
|response to metal ion|
|response to oxygen levels|
|regulation of protein catabolic process|
|response to oxidative stress|
|cofactor metabolic process|
|response to radiation|
|neutrophil degranulation|
|neutrophil activation involved in immune response|
|response to nutrient levels|
|neutrophil mediated immunity|
|neutrophil activation|
|granulocyte activation|
|response to toxic substance|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|protein complex oligomerization|
|myeloid cell activation involved in immune response|
|response to extracellular stimulus|
|response to inorganic substance|
|myeloid leukocyte activation|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|response to bacterium|
|regulated exocytosis|
|regulation of proteolysis|
|leukocyte mediated immunity|
|exocytosis|
|regulation of cellular catabolic process|
|zinc ion binding|
|response to lipid|
|response to hormone|
|response to organic cyclic compound|
|leukocyte activation|
|regulation of catabolic process|
|response to organonitrogen compound|
|secretion by cell|
|cellular response to cytokine stimulus|
|response to drug|
|negative regulation of cellular protein metabolic process|
|export from cell|
|identical protein binding|
|cell activation|
|response to nitrogen compound|
|immune effector process|
|response to cytokine|
|negative regulation of protein metabolic process|
|secretion|
|response to abiotic stimulus|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|response to biotic stimulus|
|organonitrogen compound biosynthetic process|
|response to endogenous stimulus|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|cellular nitrogen compound biosynthetic process|
|protein-containing complex subunit organization|
|immune response|
|extracellular region|
|vesicle-mediated 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:exp148|SB202190 10μM R03 exp148]]|-2.3|
|[[:results:exp114|A-196 10μM R03 exp114]]|-2.13|
|[[:results:exp306|Rapamycin 2μM R07 exp306]]|1.7|
|[[:results:exp422|Wiskostatin 3μM R07 exp422]]|1.71|
|[[:results:exp224|CB-839 10μM R05 exp224]]|1.77|
|[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|1.8|
|[[:results:exp187|proTAME 5μM R04 exp187]]|1.82|
|[[:results:exp423|Zebularine 20μM R07 exp423]]|1.83|
|[[:results:exp332|Adefovir 20μM R07 exp332]]|1.85|
|[[:results:exp160|Ribavirin 10 to 15μM on day4 R04 exp160]]|1.85|
|[[:results:exp529|Thimerosal 0.85μM R08 exp529]]|1.85|
|[[:results:exp227|Cryptotanshinone 12μM R05 exp227]]|1.86|
|[[:results:exp363|GSK-J4 1-1.25μM to day4 R07 exp363]]|1.86|
|[[:results:exp362|GSK-J4 1μM R07 exp362]]|1.86|
|[[:results:exp343|Centrinone 0.5μM R07 exp343]]|1.87|
|[[:results:exp431|Rotenone 0.07μM R08 exp431]]|1.89|
|[[:results:exp351|Dexamethasone 0.006μM R07 exp351]]|1.95|
|[[:results:exp391|Pomalidomide 20μM R07 exp391]]|1.96|
|[[:results:exp321|ABT-702 5μM plus Deferoxamine 11μM R07 exp321]]|1.97|
|[[:results:exp177|Apcin 25μM plus proTAME 2μM R04 exp177]]|2.04|
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|2.09|
|[[:results:exp344|Chlorpromazine 10μM R07 exp344]]|2.09|
|[[:results:exp180|Dynasore 10μM R04 exp180]]|2.19|
|[[:results:exp275|Citral 75μM R06 exp275]]|2.24|
|[[:results:exp436|Dynasore 7μM R08 exp436]]|2.26|
|[[:results:exp348|Cyclosporin-A 3μM R07 exp348]]|2.29|
|[[:results:exp84|UM0125461 0.74μM R02 exp84]]|2.45|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|3.02|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|3.26|
|[[:results:exp450|Artemisinin 50μM R08 exp450]]|8.42|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hmbs|HMBS]]|0.64|
|[[:human genes:p:ppox|PPOX]]|0.519|
|[[:human genes:a:alas1|ALAS1]]|0.519|
|[[:human genes:c:cpox|CPOX]]|0.477|
|[[:human genes:f:fech|FECH]]|0.45|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 2/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1582
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.31 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='ALAD Expression in NALM6 Cells: 5.31'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>