LOCUS       NM_000536               2388 bp    mRNA    linear   PRI 12-FEB-2025
DEFINITION  Homo sapiens recombination activating 2 (RAG2), transcript variant
            1, mRNA.
ACCESSION   NM_000536
VERSION     NM_000536.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2388)
  AUTHORS   Taghizadeh Mortezaei,N., Mohammadi,S., Abolhassani,H., Shokri,S.,
            Nabavi,M., Fallahpour,M. and Bemanian,M.H.
  TITLE     From variant of uncertain significance to likely pathogenic in two
            siblings with atypical RAG2 Deficiency: a case report and review of
            the literature
  JOURNAL   BMC Pediatr 24 (1), 116 (2024)
   PUBMED   38350907
  REMARK    GeneRIF: From variant of uncertain significance to likely
            pathogenic in two siblings with atypical RAG2 Deficiency: a case
            report and review of the literature.
            Review article
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2388)
  AUTHORS   Karaatmaca,B., Cagdas,D., Esenboga,S., Erman,B., Tan,C., Turul
            Ozgur,T., Boztug,K., van der Burg,M., Sanal,O. and Tezcan,I.
  TITLE     Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a
            single-centre
  JOURNAL   Clin Exp Immunol 215 (2), 160-176 (2024)
   PUBMED   37724703
  REMARK    GeneRIF: Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a
            single-centre.
REFERENCE   3  (bases 1 to 2388)
  AUTHORS   Jabbarpour,N., Bonyadi,M. and Sadeghi,L.
  TITLE     A novel loss of function mutation in the PHD domain of the RAG2
            gene, affecting zinc-binding affinity
  JOURNAL   Mol Biol Rep 50 (10), 8771-8775 (2023)
   PUBMED   37573280
  REMARK    GeneRIF: A novel loss of function mutation in the PHD domain of the
            RAG2 gene, affecting zinc-binding affinity.
REFERENCE   4  (bases 1 to 2388)
  AUTHORS   Schuetz,C., Gerke,J., Ege,M., Walter,J., Kusters,M., Worth,A.,
            Kanakry,J.A., Dimitrova,D., Wolska-Kusnierz,B., Chen,K., Unal,E.,
            Karakukcu,M., Pashchenko,O., Leiding,J., Kawai,T., Amrolia,P.J.,
            Berghuis,D., Buechner,J., Buchbinder,D., Cowan,M.J., Gennery,A.R.,
            Gungor,T., Heimall,J., Miano,M., Meyts,I., Morris,E.C., Riviere,J.,
            Sharapova,S.O., Shaw,P.J., Slatter,M., Honig,M., Veys,P.,
            Fischer,A., Cavazzana,M., Moshous,D., Schulz,A., Albert,M.H.,
            Puck,J.M., Lankester,A.C., Notarangelo,L.D. and Neven,B.
  TITLE     Hypomorphic RAG deficiency: impact of disease burden on survival
            and thymic recovery argues for early diagnosis and HSCT
  JOURNAL   Blood 141 (7), 713-724 (2023)
   PUBMED   36279417
  REMARK    GeneRIF: Hypomorphic RAG deficiency: impact of disease burden on
            survival and thymic recovery argues for early diagnosis and HSCT.
REFERENCE   5  (bases 1 to 2388)
  AUTHORS   Jin,M., Alam,M.M., Liu,A.Y. and Jiang,P.
  TITLE     Rag2-/- accelerates lipofuscin accumulation in the brain:
            Implications for human stem cell brain transplantation studies
  JOURNAL   Stem Cell Reports 17 (11), 2381-2391 (2022)
   PUBMED   36270284
  REMARK    GeneRIF: Rag2(-/-) accelerates lipofuscin accumulation in the
            brain: Implications for human stem cell brain transplantation
            studies.
            Erratum:[Stem Cell Reports. 2023 Jan 10;18(1):413-415. doi:
            10.1016/j.stemcr.2022.11.023.. PMID: 36630907]
REFERENCE   6  (bases 1 to 2388)
  AUTHORS   Lynch,S., Kelleher,D., McManus,R. and O'Farrelly,C.
  TITLE     RAG1 and RAG2 expression in human intestinal epithelium: evidence
            of extrathymic T cell differentiation
  JOURNAL   Eur J Immunol 25 (5), 1143-1147 (1995)
   PUBMED   7774617
REFERENCE   7  (bases 1 to 2388)
  AUTHORS   Sherrington,P.D., Forster,A., Seawright,A., van Heyningen,V. and
            Rabbitts,T.H.
  TITLE     Human RAG2, like RAG1, is on chromosome 11 band p13 and therefore
            not linked to ataxia telangiectasia complementation groups
  JOURNAL   Genes Chromosomes Cancer 5 (4), 404-406 (1992)
   PUBMED   1283330
REFERENCE   8  (bases 1 to 2388)
  AUTHORS   Ichihara,Y., Hirai,M. and Kurosawa,Y.
  TITLE     Sequence and chromosome assignment to 11p13-p12 of human RAG genes
  JOURNAL   Immunol Lett 33 (3), 277-284 (1992)
   PUBMED   1428003
REFERENCE   9  (bases 1 to 2388)
  AUTHORS   Bories,J.C., Cayuela,J.M., Loiseau,P. and Sigaux,F.
  TITLE     Expression of human recombination activating genes (RAG1 and RAG2)
            in neoplastic lymphoid cells: correlation with cell differentiation
            and antigen receptor expression
  JOURNAL   Blood 78 (8), 2053-2061 (1991)
   PUBMED   1832998
REFERENCE   10 (bases 1 to 2388)
  AUTHORS   Oettinger,M.A., Schatz,D.G., Gorka,C. and Baltimore,D.
  TITLE     RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J
            recombination
  JOURNAL   Science 248 (4962), 1517-1523 (1990)
   PUBMED   2360047
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB146077.1, AK292664.1,
            AW058148.1 and BC022397.1.
            
            On Jun 2, 2019 this sequence version replaced NM_000536.3.
            
            Summary: 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 Variant: This variant (1) represents the shortest
            transcript. Variants 1, 3 and 4 encode the same protein.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC022397.1, AK292664.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA2144120
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000311485.8/ ENSP00000308620.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-9                 DB146077.1         44-52
            10-2073             AK292664.1         3-2066
            2074-2145           AW058148.1         1-72                c
            2146-2388           BC022397.1         2146-2388
FEATURES             Location/Qualifiers
     source          1..2388
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11p12"
     gene            1..2388
                     /gene="RAG2"
                     /gene_synonym="RAG-2"
                     /note="recombination activating 2"
                     /db_xref="GeneID:5897"
                     /db_xref="HGNC:HGNC:9832"
                     /db_xref="MIM:179616"
     exon            1..135
                     /gene="RAG2"
                     /gene_synonym="RAG-2"
                     /inference="alignment:Splign:2.1.0"
     exon            136..2388
                     /gene="RAG2"
                     /gene_synonym="RAG-2"
                     /inference="alignment:Splign:2.1.0"
     CDS             163..1746
                     /gene="RAG2"
                     /gene_synonym="RAG-2"
                     /note="recombination activating gene 2"
                     /codon_start=1
                     /product="V(D)J recombination-activating protein 2"
                     /protein_id="NP_000527.2"
                     /db_xref="CCDS:CCDS7903.1"
                     /db_xref="GeneID:5897"
                     /db_xref="HGNC:HGNC:9832"
                     /db_xref="MIM:179616"
                     /translation="MSLQMVTVSNNIALIQPGFSLMNFDGQVFFFGQKGWPKRSCPTG
                     VFHLDVKHNHVKLKPTIFSKDSCYLPPLRYPATCTFKGSLESEKHQYIIHGGKTPNNE
                     VSDKIYVMSIVCKNNKKVTFRCTEKDLVGDVPEARYGHSINVVYSRGKSMGVLFGGRS
                     YMPSTHRTTEKWNSVADCLPCVFLVDFEFGCATSYILPELQDGLSFHVSIAKNDTIYI
                     LGGHSLANNIRPANLYRIRVDLPLGSPAVNCTVLPGGISVSSAILTQTNNDEFVIVGG
                     YQLENQKRMICNIISLEDNKIEIREMETPDWTPDIKHSKIWFGSNMGNGTVFLGIPGD
                     NKQVVSEGFYFYMLKCAEDDTNEEQTTFTNSQTSTEDPGDSTPFEDSEEFCFSAEANS
                     FDGDDEFDTYNEDDEEDESETGYWITCCPTCDVDINTWVPFYSTELNKPAMIYCSHGD
                     GHWVHAQCMDLAERTLIHLSAGSNKYYCNEHVEIARALHTPQRVLPLKKPPMKSLRKK
                     GSGKILTPAKKSFLRRLFD"
     regulatory      1910..1915
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RAG2"
                     /gene_synonym="RAG-2"
                     /note="hexamer: AATAAA"
     polyA_site      1931
                     /gene="RAG2"
                     /gene_synonym="RAG-2"
     regulatory      2126..2131
                     /regulatory_class="polyA_signal_sequence"
                     /gene="RAG2"
                     /gene_synonym="RAG-2"
                     /note="hexamer: AAGAAA"
     polyA_site      2144
                     /gene="RAG2"
                     /gene_synonym="RAG-2"
                     /note="major polyA site"
ORIGIN      
        1 actctcttta cagtcagcct tctgcttgcc acagtcatag tgggcagtca gtgaatcttc
       61 cccaagtgct gacaattaat acctggttta gcggcaaaga ttcagagagg cgtgagcagc
      121 ccctctggcc ttcagacaaa aatctacgta ccatcagaaa ctatgtctct gcagatggta
      181 acagtcagta ataacatagc cttaattcag ccaggcttct cactgatgaa ttttgatgga
      241 caagttttct tctttggaca aaaaggctgg cccaaaagat cctgccccac tggagttttc
      301 catctggatg taaagcataa ccatgtcaaa ctgaagccta caattttctc taaggattcc
      361 tgctacctcc ctcctcttcg ctacccagcc acttgcacat tcaaaggcag cttggagtct
      421 gaaaagcatc aatacatcat ccatggaggg aaaacaccaa acaatgaggt ttcagataag
      481 atttatgtca tgtctattgt ttgcaagaac aacaaaaagg ttacttttcg ctgcacagag
      541 aaagacttgg taggagatgt tcctgaagcc agatatggtc attccattaa tgtggtgtac
      601 agccgaggga aaagtatggg tgttctcttt ggaggacgct catacatgcc ttctacccac
      661 agaaccacag aaaaatggaa tagtgtagct gactgcctgc cctgtgtttt cctggtggat
      721 tttgaatttg ggtgtgctac atcatacatt cttccagaac ttcaggatgg gctatctttt
      781 catgtctcta ttgccaaaaa tgacaccatc tatattttag gaggacattc acttgccaat
      841 aatatccggc ctgccaacct gtacagaata agggttgatc ttcccctggg tagcccagct
      901 gtgaattgca cagtcttgcc aggaggaatc tctgtctcca gtgcaatcct gactcaaact
      961 aacaatgatg aatttgttat tgttggtggc tatcagcttg aaaatcaaaa aagaatgatc
     1021 tgcaacatca tctctttaga ggacaacaag atagaaattc gtgagatgga gaccccagat
     1081 tggaccccag acattaagca cagcaagata tggtttggaa gcaacatggg aaatggaact
     1141 gtttttcttg gcataccagg agacaataaa caagttgttt cagaaggatt ctatttctat
     1201 atgttgaaat gtgctgaaga tgatactaat gaagagcaga caacattcac aaacagtcaa
     1261 acatcaacag aagatccagg ggattccact ccctttgaag actctgaaga attttgtttc
     1321 agtgcagaag caaatagttt tgatggtgat gatgaatttg acacctataa tgaagatgat
     1381 gaagaagatg agtctgagac aggctactgg attacatgct gccctacttg tgatgtggat
     1441 atcaacactt gggtaccatt ctattcaact gagctcaaca aacccgccat gatctactgc
     1501 tctcatgggg atgggcactg ggtccatgct cagtgcatgg atctggcaga acgcacactc
     1561 atccatctgt cagcaggaag caacaagtat tactgcaatg agcatgtgga gatagcaaga
     1621 gctctacaca ctccccaaag agtcctaccc ttaaaaaagc ctccaatgaa atccctccgt
     1681 aaaaaaggtt ctggaaaaat cttgactcct gccaagaaat cctttcttag aaggttgttt
     1741 gattagtttt gcaaaagcct ttcagattca ggtgtatgga atttttgaat ctatttttaa
     1801 aatcataaca ttgattttaa aaatacattt ttgtttattt aaaatgccta tgttttcttt
     1861 tagttacatg aattaagggc cagaaaaaag tgtttataat gcaatgataa ataaagtcat
     1921 tctagaccct atacattttg aaaatatttt acccaaatac tcaatttact aatttattct
     1981 tcactgagga tttctgatct gattttttat tcaacaaacc ttaaacaccc agaagcagta
     2041 ataatcatcg aggtatgttt atatttatta tataagtctt ggtaacaaat aacctataaa
     2101 gtgtttatga caaatttagc caataaagaa attaacaccc aaaagaatta aattgattat
     2161 tttgtgcaac ataacaattc ggcagttggc caaaacttaa aagcaagatc tactacatcc
     2221 cacattagtg ttctttatat accttcaagc aaccctttgg attatgccca tgaacaagtt
     2281 agtttctcat agctttacag atgtagatat aaatataaat atatgtatac atatagatag
     2341 ataatgttct ccactgacac aaaagaagaa ataaataatc tacatcaa
//
