RAG1 [The Human Chemical-Genetic Interaction Map Project]

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======= RAG1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RAG1
  * **<color #00a2e8>Official Name</color>**: recombination activating 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5896|5896]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P15918|P15918]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RAG1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RAG1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/179615|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is involved in activation of immunoglobulin V-D-J recombination. The encoded protein is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG2. Defects in this gene can be the cause of several diseases. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T- lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'- hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'- phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1 (By similarity). {ECO:0000250}.

<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'>
|zf-RAG1|
|RAG1|
|zf-C3HC4|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|double-stranded DNA endodeoxyribonuclease activity|
|endodeoxyribonuclease complex|
|DNA recombinase complex|
|pre-B cell allelic exclusion|
|pre-B cell differentiation|
|negative regulation of thymocyte apoptotic process|
|regulation of behavioral fear response|
|immature B cell differentiation|
|regulation of fear response|
|regulation of thymocyte apoptotic process|
|V(D)J recombination|
|negative regulation of T cell apoptotic process|
|negative regulation of lymphocyte apoptotic process|
|histone monoubiquitination|
|regulation of T cell apoptotic process|
|T cell homeostasis|
|somatic diversification of immune receptors via germline recombination within a single locus|
|somatic cell DNA recombination|
|endonuclease activity|
|histone ubiquitination|
|thymus development|
|negative regulation of leukocyte apoptotic process|
|T cell differentiation in thymus|
|visual learning|
|somatic diversification of immune receptors|
|regulation of lymphocyte apoptotic process|
|visual behavior|
|lymphocyte homeostasis|
|protein monoubiquitination|
|protein autoubiquitination|
|leukocyte homeostasis|
|regulation of behavior|
|associative learning|
|negative regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of T cell differentiation|
|regulation of leukocyte apoptotic process|
|negative regulation of cysteine-type endopeptidase activity|
|positive regulation of lymphocyte differentiation|
|B cell differentiation|
|histone binding|
|T cell differentiation|
|regulation of T cell differentiation|
|learning|
|positive regulation of leukocyte differentiation|
|B cell activation|
|regulation of lymphocyte differentiation|
|positive regulation of hemopoiesis|
|homeostasis of number of cells|
|positive regulation of T cell activation|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of leukocyte cell-cell adhesion|
|ubiquitin protein ligase activity|
|DNA recombination|
|T cell activation|
|lymphocyte differentiation|
|regulation of cysteine-type endopeptidase activity|
|negative regulation of endopeptidase activity|
|ubiquitin-protein transferase activity|
|positive regulation of cell-cell adhesion|
|negative regulation of peptidase activity|
|learning or memory|
|regulation of leukocyte differentiation|
|regulation of leukocyte cell-cell adhesion|
|nucleic acid phosphodiester bond hydrolysis|
|cognition|
|response to light stimulus|
|regulation of T cell activation|
|leukocyte differentiation|
|negative regulation of proteolysis|
|positive regulation of lymphocyte activation|
|histone modification|
|covalent chromatin modification|
|lymphocyte activation|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of leukocyte activation|
|gland development|
|regulation of endopeptidase activity|
|positive regulation of cell activation|
|sequence-specific DNA binding|
|response to radiation|
|regulation of peptidase activity|
|regulation of hemopoiesis|
|negative regulation of hydrolase activity|
|regulation of lymphocyte activation|
|hemopoiesis|
|behavior|
|regulation of leukocyte activation|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|regulation of cell activation|
|immune system development|
|regulation of cell adhesion|
|protein ubiquitination|
|chromatin organization|
|regulation of proteolysis|
|DNA metabolic process|
|regulation of defense response|
|protein modification by small protein conjugation|
|negative regulation of catalytic activity|
|zinc ion binding|
|protein homodimerization activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|leukocyte activation|
|positive regulation of cell differentiation|
|protein modification by small protein conjugation or removal|
|negative regulation of cell death|
|negative regulation of cellular protein metabolic process|
|chromosome organization|
|cell activation|
|negative regulation of protein metabolic process|
|negative regulation of molecular function|
|positive regulation of immune system process|
|response to abiotic stimulus|
|regulation of hydrolase activity|
|positive regulation of developmental process|
|nervous system process|
|DNA binding|
|regulation of response to stress|
|regulation of apoptotic process|
|regulation of programmed cell death|
|homeostatic process|
|regulation of immune system process|
|regulation of cell death|
|positive regulation of multicellular organismal process|
|regulation of cell differentiation|
|immune response|
|system process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' 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:exp308|Rapamycin 2μM plus FK-506 5μM R07 exp308]]|1.81|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 19006
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 9.38 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RAG1 Expression in NALM6 Cells: 9.38'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>