Human Gene RAG2 (uc001mwv.4) Description and Page Index
  Description: Homo sapiens recombination activating gene 2 (RAG2), transcript variant 1, mRNA.
RefSeq Summary (NM_000536): This gene encodes a protein that is involved in the initiation of V(D)J recombination during B and T cell development. This protein forms a complex with the product of the adjacent recombination activating gene 1, and this complex can form double-strand breaks by cleaving DNA at conserved recombination signal sequences. The recombination activating gene 1 component is thought to contain most of the catalytic activity, while the N-terminal of the recombination activating gene 2 component is thought to form a six-bladed propeller in the active core that serves as a binding scaffold for the tight association of the complex with DNA. A C-terminal plant homeodomain finger-like motif in this protein is necessary for interactions with chromatin components, specifically with histone H3 that is trimethylated at lysine 4. Mutations in this gene cause Omenn syndrome, a form of severe combined immunodeficiency associated with autoimmune-like symptoms. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr11:36,613,493-36,619,829 Size: 6,337 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg19 chr11:36,614,135-36,615,718 Size: 1,584 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:36,613,493-36,619,829)mRNA (may differ from genome)Protein (527 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: RAG2_HUMAN
DESCRIPTION: RecName: Full=V(D)J recombination-activating protein 2; Short=RAG-2;
FUNCTION: Core 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. DNA cleavage by the RAG complex 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 the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3 (By similarity).
SUBUNIT: Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By similarity).
SUBCELLULAR LOCATION: Nucleus (By similarity).
TISSUE SPECIFICITY: Cells of the B- and T-lymphocyte lineages.
DOMAIN: The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr- 445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3) (By similarity).
DISEASE: Defects in RAG2 are a cause of combined cellular and humoral immune defects with granulomas (CHIDG) [MIM:233650]. CHIDG is an immunodeficiency disease with granulomas in the skin, mucous membranes, and internal organs. Other characteristics include hypogammaglobulinemia, a diminished number of T and B-cells, and sparse thymic tissue on ultrasonography.
DISEASE: Defects in RAG2 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- negative/NK-cell-positive (T(-)B(-)NK(+) SCID) [MIM:601457]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.
DISEASE: Defects in RAG2 are a cause of Omenn syndrome (OS) [MIM:603554]. OS is a severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels.
SIMILARITY: Belongs to the RAG2 family.
SIMILARITY: Contains 1 PHD-type zinc finger.
WEB RESOURCE: Name=RAG2base; Note=RAG2 deficiency database; URL="http://bioinf.uta.fi/RAG2base/";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RAG2";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): RAG2
CDC HuGE Published Literature: RAG2

-  MalaCards Disease Associations
  MalaCards Gene Search: RAG2
Diseases sorted by gene-association score: omenn syndrome* (1720), combined cellular and humoral immune defects with granulomas* (1681), severe combined immunodeficiency, b cell-negative* (1096), severe combined immune deficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive, rag1/rag2-related* (500), malignant histiocytosis* (283), severe combined immunodeficiency (28), recombinase activating gene 1 deficiency (13), primary immunodeficiency disease (9), severe combined immune deficiency (8), combined t cell and b cell immunodeficiency (6), gastroduodenitis (6), brain germinoma (5), lig4 syndrome (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 0.21 RPKM in Thyroid
Total median expression: 0.21 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -50.60205-0.247 Picture PostScript Text
3' UTR -108.25642-0.169 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011043 - Gal_Oxase/kelch_b-propeller
IPR015915 - Kelch-typ_b-propeller
IPR004321 - RAG2
IPR025162 - RAG2_PHD

Pfam Domains:
PF03089 - Recombination activating protein 2
PF13341 - RAG2 PHD domain

ModBase Predicted Comparative 3D Structure on P55895
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding
GO:0008270 zinc ion binding
GO:0035064 methylated histone binding
GO:0035091 phosphatidylinositol binding
GO:0043325 phosphatidylinositol-3,4-bisphosphate binding
GO:0046872 metal ion binding
GO:0061630 ubiquitin protein ligase activity
GO:0080025 phosphatidylinositol-3,5-bisphosphate binding

Biological Process:
GO:0002326 B cell lineage commitment
GO:0002331 pre-B cell allelic exclusion
GO:0002358 B cell homeostatic proliferation
GO:0002360 T cell lineage commitment
GO:0006310 DNA recombination
GO:0006325 chromatin organization
GO:0016567 protein ubiquitination
GO:0030183 B cell differentiation
GO:0030217 T cell differentiation
GO:0033077 T cell differentiation in thymus
GO:0033151 V(D)J recombination
GO:0042742 defense response to bacterium
GO:0046622 positive regulation of organ growth

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm


-  Descriptions from all associated GenBank mRNAs
  BC022397 - Homo sapiens recombination activating gene 2, mRNA (cDNA clone MGC:24118 IMAGE:4656700), complete cds.
JD348964 - Sequence 329988 from Patent EP1572962.
JD058840 - Sequence 39864 from Patent EP1572962.
AK292664 - Homo sapiens cDNA FLJ75861 complete cds, highly similar to Homo sapiens recombination activating gene 2 (RAG2), mRNA.
JD244798 - Sequence 225822 from Patent EP1572962.
JD296568 - Sequence 277592 from Patent EP1572962.
AF080577 - Homo sapiens RAG2 mRNA, partial cds.
JD195641 - Sequence 176665 from Patent EP1572962.
JD344856 - Sequence 325880 from Patent EP1572962.
DQ892012 - Synthetic construct clone IMAGE:100004642; FLH182295.01X; RZPDo839E09138D recombination activating gene 2 (RAG2) gene, encodes complete protein.
KJ897444 - Synthetic construct Homo sapiens clone ccsbBroadEn_06838 RAG2 gene, encodes complete protein.
KR711197 - Synthetic construct Homo sapiens clone CCSBHm_00021069 RAG2 (RAG2) mRNA, encodes complete protein.
KR711198 - Synthetic construct Homo sapiens clone CCSBHm_00021075 RAG2 (RAG2) mRNA, encodes complete protein.
KR711199 - Synthetic construct Homo sapiens clone CCSBHm_00021077 RAG2 (RAG2) mRNA, encodes complete protein.
KR711200 - Synthetic construct Homo sapiens clone CCSBHm_00021083 RAG2 (RAG2) mRNA, encodes complete protein.
DQ895201 - Synthetic construct Homo sapiens clone IMAGE:100009661; FLH182291.01L; RZPDo839E09137D recombination activating gene 2 (RAG2) gene, encodes complete protein.
AB464686 - Synthetic construct DNA, clone: pF1KB9875, Homo sapiens RAG2 gene for recombination activating gene 2, without stop codon, in Flexi system.
S78372 - RAG2=recombination activation gene 2 [human, bone marrow, mRNA Partial, 148 nt].
JD508526 - Sequence 489550 from Patent EP1572962.
JD163582 - Sequence 144606 from Patent EP1572962.
JD528795 - Sequence 509819 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05340 - Primary immunodeficiency

Reactome (by CSHL, EBI, and GO)

Protein P55895 (Reactome details) participates in the following event(s):

R-HSA-1266695 Interleukin-7 signaling
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-449147 Signaling by Interleukins
R-HSA-5683057 MAPK family signaling cascades
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-162582 Signal Transduction
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A8K9E9, NM_000536, NP_001230715, P55895, Q8TBL4, RAG2_HUMAN
UCSC ID: uc001mwv.4
RefSeq Accession: NM_000536
Protein: P55895 (aka RAG2_HUMAN)
CCDS: CCDS7903.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000536.3
exon count: 2CDS single in 3' UTR: no RNA size: 2457
ORF size: 1584CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3368.00frame shift in genome: no % Coverage: 98.94
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.