Human Gene RAG1 (ENST00000299440.6) from GENCODE V44
  Description: Homo sapiens recombination activating 1 (RAG1), transcript variant 1, mRNA. (from RefSeq NM_000448)
RefSeq Summary (NM_000448): 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].
Gencode Transcript: ENST00000299440.6
Gencode Gene: ENSG00000166349.11
Transcript (Including UTRs)
   Position: hg38 chr11:36,568,007-36,579,762 Size: 11,756 Total Exon Count: 2 Strand: +
Coding Region
   Position: hg38 chr11:36,573,305-36,576,436 Size: 3,132 Coding Exon Count: 1 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:36,568,007-36,579,762)mRNA (may differ from genome)Protein (1043 aa)
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OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: RAG1_HUMAN
DESCRIPTION: RecName: Full=V(D)J recombination-activating protein 1; Short=RAG-1; AltName: Full=RING finger protein 74; Includes: RecName: Full=Endonuclease RAG1; EC=3.1.-.-; Includes: RecName: Full=E3 ubiquitin-protein ligase RAG1; EC=6.3.2.-;
FUNCTION: 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 a 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).
COFACTOR: Binds 1 divalent metal cation per subunit. Magnesium or manganese (By similarity).
SUBUNIT: Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By similarity).
INTERACTION: P16333:NCK1; NbExp=2; IntAct=EBI-1755109, EBI-389883;
SUBCELLULAR LOCATION: Nucleus (By similarity).
TISSUE SPECIFICITY: Maturing lymphoid cells.
DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin- protein ligase activity (By similarity).
DOMAIN: The NBD (nonamer binding) DNA-binding domain mediates the specific binding to the nonamer RSS motif by forming a tightly interwoven homodimer that binds and synapses 2 nonamer elements, with each NBD making contact with both DNA molecules. Each RSS is composed of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either 12 bp or 23 bp (By similarity).
PTM: Autoubiquitinated in the presence of CDC34/UBCH3 (By similarity).
DISEASE: Defects in RAG1 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 RAG1 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 RAG1 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.
DISEASE: Defects in RAG1 are the cause of alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion severe cytomegalovirus infection and autoimmunity (T-CMVA) [MIM:609889]. An immunological disorder characterized by oligoclonal expansion of TCR gamma/delta T-cells, TCR alpha/beta T-cell lymphopenia, severe, disseminated cytomegalovirus infection and autoimmune cytopenia.
SIMILARITY: Belongs to the RAG1 family.
SIMILARITY: Contains 1 NBD (nonamer binding) DNA-binding domain.
SIMILARITY: Contains 1 RAG1-type zinc finger.
SIMILARITY: Contains 1 RING-type zinc finger.
SEQUENCE CAUTION: Sequence=AAM77798.1; Type=Erroneous gene model prediction;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RAG1";
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/rag1/";
WEB RESOURCE: Name=RAG1base; Note=RAG1 deficiency database; URL="http://bioinf.uta.fi/RAG1base/";
WEB RESOURCE: Name=Mendelian genes recombination activating gene 1 (RAG1); Note=Leiden Open Variation Database (LOVD); URL="http://www.lovd.nl/RAG1";

-  Primer design for this transcript
 

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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: RAG1
Diseases sorted by gene-association score: alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity* (1582), severe combined immunodeficiency, b cell-negative* (1550), combined cellular and humoral immune defects with granulomas* (1118), omenn syndrome* (988), malignant histiocytosis* (400), severe combined immune deficiency, autosomal recessive, t cell-negative, b cell-negative, nk cell-positive, rag1/rag2-related* (354), lymphopenia (43), cytomegalovirus infection (29), recombinase activating gene 1 deficiency (23), severe combined immunodeficiency (22), artemis deficiency (9), combined t cell and b cell immunodeficiency (8), baylisascariasis (8), immunodeficiency with hyper-igm, type 3 (6), progressive multifocal leukoencephalopathy (6), salivary gland disease (5), sialadenitis (4), hereditary neuropathies (4), lig4 syndrome (4), primary immunodeficiency disease (3), common variable immunodeficiency (2), leukemia, acute lymphoblastic (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 0.39 RPKM in Spleen
Total median expression: 2.57 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 -35.60130-0.274 Picture PostScript Text
3' UTR -801.503326-0.241 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
IPR024627 - RAG1
IPR023336 - RAG_nonamer-bd_dom
IPR015880 - Znf_C2H2-like
IPR013087 - Znf_C2H2/integrase_DNA-bd
IPR001841 - Znf_RING
IPR013083 - Znf_RING/FYVE/PHD
IPR017907 - Znf_RING_CS
IPR019485 - Znf_VDJ_recomb-activ_1

Pfam Domains:
PF12940 - Recombination-activation protein 1 (RAG1), recombinase
PF10426 - Recombination-activating protein 1 zinc-finger domain

ModBase Predicted Comparative 3D Structure on P15918
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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
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0003824 catalytic activity
GO:0004518 nuclease activity
GO:0004519 endonuclease activity
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0016740 transferase activity
GO:0016787 hydrolase activity
GO:0042393 histone binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding
GO:0061630 ubiquitin protein ligase activity

Biological Process:
GO:0002250 adaptive immune response
GO:0002331 pre-B cell allelic exclusion
GO:0006310 DNA recombination
GO:0006325 chromatin organization
GO:0006955 immune response
GO:0008152 metabolic process
GO:0008542 visual learning
GO:0010390 histone monoubiquitination
GO:0030183 B cell differentiation
GO:0033077 T cell differentiation in thymus
GO:0033151 V(D)J recombination
GO:0043029 T cell homeostasis
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045580 regulation of T cell differentiation
GO:0045582 positive regulation of T cell differentiation
GO:0048538 thymus development
GO:0051865 protein autoubiquitination
GO:0070233 negative regulation of T cell apoptotic process
GO:0070244 negative regulation of thymocyte apoptotic process
GO:0090305 nucleic acid phosphodiester bond hydrolysis
GO:2000822 regulation of behavioral fear response

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm


-  Descriptions from all associated GenBank mRNAs
  BC037344 - Homo sapiens recombination activating gene 1, mRNA (cDNA clone MGC:43321 IMAGE:5265661), complete cds.
M29474 - Human recombination activating protein (RAG-1) gene, complete cds.
JD066081 - Sequence 47105 from Patent EP1572962.
JD246108 - Sequence 227132 from Patent EP1572962.
CU691484 - Synthetic construct Homo sapiens gateway clone IMAGE:100021023 5' read RAG1 mRNA.
S78351 - RAG1=recombination activation gene 1 [human, whole intestine, mRNA Partial, 170 nt].
JD527211 - Sequence 508235 from Patent EP1572962.
JD067715 - Sequence 48739 from Patent EP1572962.
JD364962 - Sequence 345986 from Patent EP1572962.
JD320221 - Sequence 301245 from Patent EP1572962.
JD096264 - Sequence 77288 from Patent EP1572962.
JD362562 - Sequence 343586 from Patent EP1572962.
JD499459 - Sequence 480483 from Patent EP1572962.
JD038211 - Sequence 19235 from Patent EP1572962.
JD304675 - Sequence 285699 from Patent EP1572962.
JD078587 - Sequence 59611 from Patent EP1572962.
JD288556 - Sequence 269580 from Patent EP1572962.
JD146396 - Sequence 127420 from Patent EP1572962.
JD242469 - Sequence 223493 from Patent EP1572962.
JD180642 - Sequence 161666 from Patent EP1572962.
JD237668 - Sequence 218692 from Patent EP1572962.
JD062321 - Sequence 43345 from Patent EP1572962.
JD287173 - Sequence 268197 from Patent EP1572962.
JD114090 - Sequence 95114 from Patent EP1572962.
JD552197 - Sequence 533221 from Patent EP1572962.
JD084078 - Sequence 65102 from Patent EP1572962.
JD566173 - Sequence 547197 from Patent EP1572962.
JD207723 - Sequence 188747 from Patent EP1572962.
JD216603 - Sequence 197627 from Patent EP1572962.
JD392361 - Sequence 373385 from Patent EP1572962.
JD314728 - Sequence 295752 from Patent EP1572962.
JD216302 - Sequence 197326 from Patent EP1572962.
JD555151 - Sequence 536175 from Patent EP1572962.
JD307340 - Sequence 288364 from Patent EP1572962.
JD082285 - Sequence 63309 from Patent EP1572962.
JD052500 - Sequence 33524 from Patent EP1572962.
JD079019 - Sequence 60043 from Patent EP1572962.
JD059289 - Sequence 40313 from Patent EP1572962.
JD062371 - Sequence 43395 from Patent EP1572962.
JD305854 - Sequence 286878 from Patent EP1572962.
JD239000 - Sequence 220024 from Patent EP1572962.
JD048054 - Sequence 29078 from Patent EP1572962.
JD203448 - Sequence 184472 from Patent EP1572962.
JD136373 - Sequence 117397 from Patent EP1572962.

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

Reactome (by CSHL, EBI, and GO)

Protein P15918 (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: ENST00000299440.1, ENST00000299440.2, ENST00000299440.3, ENST00000299440.4, ENST00000299440.5, NM_000448, P15918, Q8NER2, RAG1_HUMAN, RNF74, uc001mwu.1, uc001mwu.2, uc001mwu.3, uc001mwu.4, uc001mwu.5, uc001mwu.6
UCSC ID: ENST00000299440.6
RefSeq Accession: NM_000448
Protein: P15918 (aka RAG1_HUMAN)
CCDS: CCDS7902.1

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