CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004389
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 V(D)J recombination-activating protein 1 
Protein Synonyms/Alias
 RAG-1; RING finger protein 74; Endonuclease RAG1; E3 ubiquitin-protein ligase RAG1 
Gene Name
 RAG1 
Gene Synonyms/Alias
 RNF74 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
702GGILRTFKFIFRGTGubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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). 
Sequence Annotation
 ZN_FING 293 332 RING-type.
 ZN_FING 354 383 RAG1-type.
 DNA_BIND 392 459 NBD.
 REGION 1 288 Interaction with importin alpha-1.
 METAL 269 269 Zinc 1 (By similarity).
 METAL 273 273 Zinc 1 (By similarity).
 METAL 293 293 Zinc 2 (By similarity).
 METAL 296 296 Zinc 1 (By similarity).
 METAL 296 296 Zinc 2 (By similarity).
 METAL 298 298 Zinc 1 (By similarity).
 METAL 308 308 Zinc 3 (By similarity).
 METAL 310 310 Zinc 3 (By similarity).
 METAL 313 313 Zinc 2 (By similarity).
 METAL 316 316 Zinc 2 (By similarity).
 METAL 328 328 Zinc 3 (By similarity).
 METAL 331 331 Zinc 3 (By similarity).
 METAL 358 358 Zinc 4 (By similarity).
 METAL 363 363 Zinc 4 (By similarity).
 METAL 375 375 Zinc 4 (By similarity).
 METAL 379 379 Zinc 4 (By similarity).
 METAL 603 603 Divalent metal cation; catalytic (By
 METAL 711 711 Divalent metal cation; catalytic (By
 METAL 965 965 Divalent metal cation; catalytic (By
 CROSSLNK 234 234 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 Chromatin regulator; Complete proteome; Disease mutation; DNA recombination; DNA-binding; Endonuclease; Hydrolase; Isopeptide bond; Ligase; Metal-binding; Multifunctional enzyme; Nuclease; Nucleus; Polymorphism; Reference proteome; SCID; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1043 AA 
Protein Sequence
MAASFPPTLG LSSAPDEIQH PHIKFSEWKF KLFRVRSFEK TPEEAQKEKK DSFEGKPSLE 60
QSPAVLDKAD GQKPVPTQPL LKAHPKFSKK FHDNEKARGK AIHQANLRHL CRICGNSFRA 120
DEHNRRYPVH GPVDGKTLGL LRKKEKRATS WPDLIAKVFR IDVKADVDSI HPTEFCHNCW 180
SIMHRKFSSA PCEVYFPRNV TMEWHPHTPS CDICNTARRG LKRKSLQPNL QLSKKLKTVL 240
DQARQARQHK RRAQARISSK DVMKKIANCS KIHLSTKLLA VDFPEHFVKS ISCQICEHIL 300
ADPVETNCKH VFCRVCILRC LKVMGSYCPS CRYPCFPTDL ESPVKSFLSV LNSLMVKCPA 360
KECNEEVSLE KYNHHISSHK ESKEIFVHIN KGGRPRQHLL SLTRRAQKHR LRELKLQVKA 420
FADKEEGGDV KSVCMTLFLL ALRARNEHRQ ADELEAIMQG KGSGLQPAVC LAIRVNTFLS 480
CSQYHKMYRT VKAITGRQIF QPLHALRNAE KVLLPGYHHF EWQPPLKNVS SSTDVGIIDG 540
LSGLSSSVDD YPVDTIAKRF RYDSALVSAL MDMEEDILEG MRSQDLDDYL NGPFTVVVKE 600
SCDGMGDVSE KHGSGPVVPE KAVRFSFTIM KITIAHSSQN VKVFEEAKPN SELCCKPLCL 660
MLADESDHET LTAILSPLIA EREAMKSSEL MLELGGILRT FKFIFRGTGY DEKLVREVEG 720
LEASGSVYIC TLCDATRLEA SQNLVFHSIT RSHAENLERY EVWRSNPYHE SVEELRDRVK 780
GVSAKPFIET VPSIDALHCD IGNAAEFYKI FQLEIGEVYK NPNASKEERK RWQATLDKHL 840
RKKMNLKPIM RMNGNFARKL MTKETVDAVC ELIPSEERHE ALRELMDLYL KMKPVWRSSC 900
PAKECPESLC QYSFNSQRFA ELLSTKFKYR YEGKITNYFH KTLAHVPEII ERDGSIGAWA 960
SEGNESGNKL FRRFRKMNAR QSKCYEMEDV LKHHWLYTSK YLQKFMNAHN ALKTSGFTMN 1020
PQASLGDPLG IEDSLESQDS MEF 1043 
Gene Ontology
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0004519; F:endonuclease activity; ISS:UniProtKB.
 GO:0042393; F:histone binding; ISS:UniProtKB.
 GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
 GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; ISS:UniProtKB.
 GO:0008270; F:zinc ion binding; ISS:UniProtKB.
 GO:0010390; P:histone monoubiquitination; ISS:UniProtKB.
 GO:0006955; P:immune response; TAS:ProtInc.
 GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Compara.
 GO:0070244; P:negative regulation of thymocyte apoptotic process; IEA:Compara.
 GO:0002331; P:pre-B cell allelic exclusion; ISS:UniProtKB.
 GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
 GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
 GO:0033151; P:V(D)J recombination; ISS:UniProtKB. 
Interpro
 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
 PF12940; RAG1
 PF10426; zf-RAG1 
SMART
 SM00184; RING
 SM00355; ZnF_C2H2 
PROSITE
 PS51487; NBD
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 
PRINTS