Human Metabolome Database: Showing Protein V(D)J recombination-activating protein 1 (HMDBP08804)

Identification Biological properties Gene properties Protein properties External links References XML Show 2 metabolites

Identification

HMDB Protein ID

HMDBP08804

Secondary Accession Numbers

14528

Name

V(D)J recombination-activating protein 1

Synonyms

E3 ubiquitin-protein ligase RAG1
Endonuclease RAG1
RAG-1
RING finger protein 74

Gene Name

RAG1

Protein Type

Unknown

Biological Properties

General Function

Involved in zinc ion binding

Specific 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

Pathways

Not Available

Reactions

Not Available

GO Classification

Component
cell part
intracellular
Function
ion binding
cation binding
metal ion binding
binding
transition metal ion binding
zinc ion binding
protein binding
nucleic acid binding

Cellular Location

Nucleus

Gene Properties

Chromosome Location

Chromosome:1

Locus

11p13

SNPs

RAG1

Gene Sequence

>3132 bp
ATGGCAGCCTCTTTCCCACCCACCTTGGGACTCAGTTCTGCCCCAGATGAAATTCAGCAC
CCACATATTAAATTTTCAGAATGGAAATTTAAGCTGTTCCGGGTGAGATCCTTTGAAAAG
ACACCTGAAGAAGCTCAAAAGGAAAAGAAGGATTCCTTTGAGGGGAAACCCTCTCTGGAG
CAATCTCCAGCAGTCCTGGACAAGGCTGATGGTCAGAAGCCAGTCCCAACTCAGCCATTG
TTAAAAGCCCACCCTAAGTTTTCAAAGAAATTTCACGACAACGAGAAAGCAAGAGGCAAA
GCGATCCATCAAGCCAACCTTCGACATCTCTGCCGCATCTGTGGGAATTCTTTTAGAGCT
GATGAGCACAACAGGAGATATCCAGTCCATGGTCCTGTGGATGGTAAAACCCTAGGCCTT
TTACGAAAGAAGGAAAAGAGAGCTACTTCCTGGCCGGACCTCATTGCCAAGGTTTTCCGG
ATCGATGTGAAGGCAGATGTTGACTCGATCCACCCCACTGAGTTCTGCCATAACTGCTGG
AGCATCATGCACAGGAAGTTTAGCAGTGCCCCATGTGAGGTTTACTTCCCGAGGAACGTG
ACCATGGAGTGGCACCCCCACACACCATCCTGTGACATCTGCAACACTGCCCGTCGGGGA
CTCAAGAGGAAGAGTCTTCAGCCAAACTTGCAGCTCAGCAAAAAACTCAAAACTGTGCTT
GACCAAGCAAGACAAGCCCGTCAGCGCAAGAGAAGAGCTCAGGCAAGGATCAGCAGCAAG
GATGTCATGAAGAAGATCGCCAACTGCAGTAAGATACATCTTAGTACCAAGCTCCTTGCA
GTGGACTTCCCAGAGCACTTTGTGAAATCCATCTCCTGCCAGATCTGTGAACACATTCTG
GCTGACCCTGTGGAGACCAACTGTAAGCATGTCTTTTGCCGGGTCTGCATTCTCAGATGC
CTCAAAGTCATGGGCAGCTATTGTCCCTCTTGCCGATATCCATGCTTCCCTACTGACCTG
GAGAGTCCAGTGAAGTCCTTTCTGAGCGTCTTGAATTCCCTGATGGTGAAATGTCCAGCA
AAAGAGTGCAATGAGGAGGTCAGTTTGGAAAAATATAATCACCACATCTCAAGTCACAAG
GAATCAAAAGAGATTTTTGTGCACATTAATAAAGGGGGCCGGCCCCGCCAACATCTTCTG
TCGCTGACTCGGAGAGCTCAGAAGCACCGGCTGAGGGAGCTCAAGCTGCAAGTCAAAGCC
TTTGCTGACAAAGAAGAAGGTGGAGATGTGAAGTCCGTGTGCATGACCTTGTTCCTGCTG
GCTCTGAGGGCGAGGAATGAGCACAGGCAAGCTGATGAGCTGGAGGCCATCATGCAGGGA
AAGGGCTCTGGCCTGCAGCCAGCTGTTTGCTTGGCCATCCGTGTCAACACCTTCCTCAGC
TGCAGTCAGTACCACAAGATGTACAGGACTGTGAAAGCCATCACAGGGAGACAGATTTTT
CAGCCTTTGCATGCCCTTCGGAATGCTGAGAAGGTACTTCTGCCAGGCTACCACCACTTT
GAGTGGCAGCCACCTCTGAAGAATGTGTCTTCCAGCACTGATGTTGGCATTATTGATGGG
CTGTCTGGACTATCATCCTCTGTGGATGATTACCCAGTGGACACCATTGCAAAGAGGTTC
CGCTATGATTCAGCTTTGGTGTCTGCTTTGATGGACATGGAAGAAGACATCTTGGAAGGC
ATGAGATCCCAAGACCTTGATGATTACCTGAATGGCCCCTTCACTGTGGTGGTGAAGGAG
TCTTGTGATGGAATGGGAGACGTGAGTGAGAAGCATGGGAGTGGGCCTGTAGTTCCAGAA
AAGGCAGTCCGTTTTTCATTCACAATCATGAAAATTACTATTGCCCACAGCTCTCAGAAT
GTGAAAGTATTTGAAGAAGCCAAACCTAACTCTGAACTGTGTTGCAAGCCATTGTGCCTT
ATGCTGGCAGATGAGTCTGACCACGAGACGCTGACTGCCATCCTGAGTCCTCTCATTGCT
GAGAGGGAGGCCATGAAGAGCAGTGAATTAATGCTTGAGCTGGGAGGCATTCTCCGGACT
TTCAAGTTCATCTTCAGGGGCACCGGCTATGATGAAAAACTTGTGCGGGAAGTGGAAGGC
CTCGAGGCTTCTGGCTCAGTCTACATTTGTACTCTTTGTGATGCCACCCGTCTGGAAGCC
TCTCAAAATCTTGTCTTCCACTCTATAACCAGAAGCCATGCTGAGAACCTGGAACGTTAT
GAGGTCTGGCGTTCCAACCCTTACCATGAGTCTGTGGAAGAACTGCGGGATCGGGTGAAA
GGGGTCTCAGCTAAACCTTTCATTGAGACAGTCCCTTCCATAGATGCACTCCACTGTGAC
ATTGGCAATGCAGCTGAGTTCTACAAGATCTTCCAGCTAGAGATAGGGGAAGTGTATAAG
AATCCCAATGCTTCCAAAGAGGAAAGGAAAAGGTGGCAGGCCACACTGGACAAGCATCTC
CGGAAGAAGATGAACCTCAAACCAATCATGAGGATGAATGGCAACTTTGCCAGGAAGCTC
ATGACCAAAGAGACTGTGGATGCAGTTTGTGAGTTAATTCCTTCCGAGGAGAGGCACGAG
GCTCTGAGGGAGCTGATGGATCTTTACCTGAAGATGAAACCAGTATGGCGATCATCATGC
CCTGCTAAAGAGTGCCCAGAATCCCTCTGCCAGTACAGTTTCAATTCACAGCGTTTTGCT
GAGCTCCTTTCTACGAAGTTCAAGTATAGGTATGAGGGAAAAATCACCAATTATTTTCAC
AAAACCCTGGCCCATGTTCCTGAAATTATTGAGAGGGATGGCTCCATTGGGGCATGGGCA
AGTGAGGGAAATGAGTCTGGTAACAAACTGTTTAGGCGCTTCCGGAAAATGAATGCCAGG
CAGTCCAAATGCTATGAGATGGAAGATGTCCTGAAACACCACTGGTTGTACACCTCCAAA
TACCTCCAGAAGTTTATGAATGCTCATAATGCATTAAAAACCTCTGGGTTTACCATGAAC
CCTCAGGCAAGCTTAGGGGACCCATTAGGCATAGAGGACTCTCTGGAAAGCCAAGATTCA
ATGGAATTTTAA

Protein Properties

Number of Residues

1043

Molecular Weight

119115.0

Theoretical pI

8.88

Pfam Domain Function

zf-RAG1 (PF10426 )

Signals

None

Transmembrane Regions

None

Protein Sequence

>V(D)J recombination-activating protein 1
MAASFPPTLGLSSAPDEIQHPHIKFSEWKFKLFRVRSFEKTPEEAQKEKKDSFEGKPSLE
QSPAVLDKADGQKPVPTQPLLKAHPKFSKKFHDNEKARGKAIHQANLRHLCRICGNSFRA
DEHNRRYPVHGPVDGKTLGLLRKKEKRATSWPDLIAKVFRIDVKADVDSIHPTEFCHNCW
SIMHRKFSSAPCEVYFPRNVTMEWHPHTPSCDICNTARRGLKRKSLQPNLQLSKKLKTVL
DQARQARQRKRRAQARISSKDVMKKIANCSKIHLSTKLLAVDFPEHFVKSISCQICEHIL
ADPVETNCKHVFCRVCILRCLKVMGSYCPSCRYPCFPTDLESPVKSFLSVLNSLMVKCPA
KECNEEVSLEKYNHHISSHKESKEIFVHINKGGRPRQHLLSLTRRAQKHRLRELKLQVKA
FADKEEGGDVKSVCMTLFLLALRARNEHRQADELEAIMQGKGSGLQPAVCLAIRVNTFLS
CSQYHKMYRTVKAITGRQIFQPLHALRNAEKVLLPGYHHFEWQPPLKNVSSSTDVGIIDG
LSGLSSSVDDYPVDTIAKRFRYDSALVSALMDMEEDILEGMRSQDLDDYLNGPFTVVVKE
SCDGMGDVSEKHGSGPVVPEKAVRFSFTIMKITIAHSSQNVKVFEEAKPNSELCCKPLCL
MLADESDHETLTAILSPLIAEREAMKSSELMLELGGILRTFKFIFRGTGYDEKLVREVEG
LEASGSVYICTLCDATRLEASQNLVFHSITRSHAENLERYEVWRSNPYHESVEELRDRVK
GVSAKPFIETVPSIDALHCDIGNAAEFYKIFQLEIGEVYKNPNASKEERKRWQATLDKHL
RKKMNLKPIMRMNGNFARKLMTKETVDAVCELIPSEERHEALRELMDLYLKMKPVWRSSC
PAKECPESLCQYSFNSQRFAELLSTKFKYRYEGKITNYFHKTLAHVPEIIERDGSIGAWA
SEGNESGNKLFRRFRKMNARQSKCYEMEDVLKHHWLYTSKYLQKFMNAHNALKTSGFTMN
PQASLGDPLGIEDSLESQDSMEF

External Links

GenBank ID Protein

190843

UniProtKB/Swiss-Prot ID

P15918

UniProtKB/Swiss-Prot Entry Name

RAG1_HUMAN

PDB IDs

1RMD

GenBank Gene ID

GeneCard ID

GenAtlas ID

HGNC ID

References

General References

Cortes P, Ye ZS, Baltimore D: RAG-1 interacts with the repeated amino acid motif of the human homologue of the yeast protein SRP1. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7633-7. [PubMed:8052633 ]
Schatz DG, Oettinger MA, Baltimore D: The V(D)J recombination activating gene, RAG-1. Cell. 1989 Dec 22;59(6):1035-48. [PubMed:2598259 ]
Nomdedeu JF, Lasa A, Seminago R, Rubiol E, Baiget M, Soler J: Two new variants of RAG-1 protein predicted by SSCP. Hum Mutat. 1996;8(2):191-2. [PubMed:8844221 ]
Schwarz K, Gauss GH, Ludwig L, Pannicke U, Li Z, Lindner D, Friedrich W, Seger RA, Hansen-Hagge TE, Desiderio S, Lieber MR, Bartram CR: RAG mutations in human B cell-negative SCID. Science. 1996 Oct 4;274(5284):97-9. [PubMed:8810255 ]
Villa A, Santagata S, Bozzi F, Giliani S, Frattini A, Imberti L, Gatta LB, Ochs HD, Schwarz K, Notarangelo LD, Vezzoni P, Spanopoulou E: Partial V(D)J recombination activity leads to Omenn syndrome. Cell. 1998 May 29;93(5):885-96. [PubMed:9630231 ]
Wada T, Takei K, Kudo M, Shimura S, Kasahara Y, Koizumi S, Kawa-Ha K, Ishida Y, Imashuku S, Seki H, Yachie A: Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders. Clin Exp Immunol. 2000 Jan;119(1):148-55. [PubMed:10606976 ]
Villa A, Sobacchi C, Notarangelo LD, Bozzi F, Abinun M, Abrahamsen TG, Arkwright PD, Baniyash M, Brooks EG, Conley ME, Cortes P, Duse M, Fasth A, Filipovich AM, Infante AJ, Jones A, Mazzolari E, Muller SM, Pasic S, Rechavi G, Sacco MG, Santagata S, Schroeder ML, Seger R, Strina D, Ugazio A, Valiaho J, Vihinen M, Vogler LB, Ochs H, Vezzoni P, Friedrich W, Schwarz K: V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. Blood. 2001 Jan 1;97(1):81-8. [PubMed:11133745 ]
de Villartay JP, Lim A, Al-Mousa H, Dupont S, Dechanet-Merville J, Coumau-Gatbois E, Gougeon ML, Lemainque A, Eidenschenk C, Jouanguy E, Abel L, Casanova JL, Fischer A, Le Deist F: A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection. J Clin Invest. 2005 Nov;115(11):3291-9. [PubMed:16276422 ]
Schuetz C, Huck K, Gudowius S, Megahed M, Feyen O, Hubner B, Schneider DT, Manfras B, Pannicke U, Willemze R, Knuchel R, Gobel U, Schulz A, Borkhardt A, Friedrich W, Schwarz K, Niehues T: An immunodeficiency disease with RAG mutations and granulomas. N Engl J Med. 2008 May 8;358(19):2030-8. doi: 10.1056/NEJMoa073966. [PubMed:18463379 ]