RAG1_DANRE
ID RAG1_DANRE Reviewed; 1057 AA.
AC O13033; Q90258;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=V(D)J recombination-activating protein 1;
DE Short=RAG-1;
DE Includes:
DE RecName: Full=Endonuclease RAG1;
DE EC=3.1.-.-;
DE Includes:
DE RecName: Full=E3 ubiquitin-protein ligase RAG1;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase RAG1 {ECO:0000305};
GN Name=rag1;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Larva;
RX PubMed=9089097; DOI=10.1007/s002510050221;
RA Willett C.E., Cherry J.J., Steiner L.A.;
RT "Characterization and expression of the recombination activating genes
RT (rag1 and rag2) of zebrafish.";
RL Immunogenetics 45:394-404(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 824-1021.
RX PubMed=7806278; DOI=10.1007/bf00188438;
RA Greenhalgh P., Steiner L.A.;
RT "Recombination activating gene 1 (Rag1) in zebrafish and shark.";
RL Immunogenetics 41:54-55(1995).
RN [3]
RP DEVELOPMENTAL STAGE.
RX PubMed=9070331; DOI=10.1006/dbio.1996.8446;
RA Willett C.E., Zapata A.G., Hopkins N., Steiner L.A.;
RT "Expression of zebrafish rag genes during early development identifies the
RT thymus.";
RL Dev. Biol. 182:331-341(1997).
CC -!- FUNCTION: Catalytic component of the RAG complex, a multiprotein
CC complex that mediates the DNA cleavage phase during V(D)J
CC recombination. V(D)J recombination assembles a diverse repertoire of
CC immunoglobulin and T-cell receptor genes in developing B and T
CC lymphocytes through rearrangement of different V (variable), in some
CC cases D (diversity), and J (joining) gene segments. In the RAG complex,
CC RAG1 mediates the DNA-binding to the conserved recombination signal
CC sequences (RSS) and catalyzes the DNA cleavage activities by
CC introducing a double-strand break between the RSS and the adjacent
CC coding segment. RAG2 is not a catalytic component but is required for
CC all known catalytic activities. DNA cleavage occurs in 2 steps: a first
CC nick is introduced in the top strand immediately upstream of the
CC heptamer, generating a 3'-hydroxyl group that can attack the
CC phosphodiester bond on the opposite strand in a direct
CC transesterification reaction, thereby creating 4 DNA ends: 2 hairpin
CC coding ends and 2 blunt, 5'-phosphorylated ends. In addition to its
CC endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase
CC that mediates monoubiquitination of histone H3. Histone H3
CC monoubiquitination is required for the joining step of V(D)J
CC recombination (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).
CC {ECO:0000250};
CC -!- SUBUNIT: Homodimer. Component of the RAG complex composed of core
CC components rag1 and rag2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00820}.
CC -!- TISSUE SPECIFICITY: In the adult, predominantly expressed in the thymus
CC with lower levels in the pronephros, mesonephros and ovary.
CC {ECO:0000269|PubMed:9089097}.
CC -!- DEVELOPMENTAL STAGE: First detected in the thymus during day 4 of
CC development. Expression then increases in the thymus for at least three
CC weeks. {ECO:0000269|PubMed:9070331, ECO:0000269|PubMed:9089097}.
CC -!- DOMAIN: The RING-type zinc finger mediates the E3 ubiquitin-protein
CC ligase activity. {ECO:0000250}.
CC -!- DOMAIN: The NBD (nonamer binding) DNA-binding domain mediates the
CC specific binding to the nonamer RSS motif by forming a tightly
CC interwoven homodimer that binds and synapses 2 nonamer elements, with
CC each NBD making contact with both DNA molecules. Each RSS is composed
CC of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer
CC (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either
CC 12 bp or 23 bp. {ECO:0000255|PROSITE-ProRule:PRU00820}.
CC -!- SIMILARITY: Belongs to the RAG1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00820}.
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DR EMBL; U71093; AAC60365.1; -; Genomic_DNA.
DR EMBL; U13983; AAA62611.1; -; Genomic_DNA.
DR PIR; I50115; I50115.
DR RefSeq; NP_571464.1; NM_131389.1.
DR PDB; 3JBW; EM; 4.63 A; A/C=271-1031.
DR PDB; 3JBX; EM; 3.40 A; A/C=271-1031.
DR PDB; 3JBY; EM; 3.70 A; A/C=271-1031.
DR PDB; 6DBI; EM; 3.36 A; A/C=271-1031.
DR PDB; 6DBJ; EM; 2.99 A; A/C=271-1031.
DR PDB; 6DBL; EM; 5.00 A; A/C=271-1031.
DR PDB; 6DBO; EM; 4.45 A; A/C=271-1031.
DR PDB; 6DBQ; EM; 4.22 A; A/C=271-1031.
DR PDB; 6DBR; EM; 4.00 A; A/C=271-1031.
DR PDB; 6DBT; EM; 4.30 A; A/C=271-1031.
DR PDB; 6DBU; EM; 3.90 A; A/C=271-1031.
DR PDB; 6DBV; EM; 4.29 A; A/C=271-1031.
DR PDB; 6DBW; EM; 4.70 A; A/C=271-1031.
DR PDB; 6DBX; EM; 4.20 A; A/C=271-1031.
DR PDBsum; 3JBW; -.
DR PDBsum; 3JBX; -.
DR PDBsum; 3JBY; -.
DR PDBsum; 6DBI; -.
DR PDBsum; 6DBJ; -.
DR PDBsum; 6DBL; -.
DR PDBsum; 6DBO; -.
DR PDBsum; 6DBQ; -.
DR PDBsum; 6DBR; -.
DR PDBsum; 6DBT; -.
DR PDBsum; 6DBU; -.
DR PDBsum; 6DBV; -.
DR PDBsum; 6DBW; -.
DR PDBsum; 6DBX; -.
DR AlphaFoldDB; O13033; -.
DR SMR; O13033; -.
DR STRING; 7955.ENSDARP00000120100; -.
DR PaxDb; O13033; -.
DR GeneID; 30663; -.
DR KEGG; dre:30663; -.
DR CTD; 5896; -.
DR ZFIN; ZDB-GENE-990415-234; rag1.
DR eggNOG; ENOG502QSFV; Eukaryota.
DR InParanoid; O13033; -.
DR OrthoDB; 85196at2759; -.
DR PhylomeDB; O13033; -.
DR PRO; PR:O13033; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0097519; C:DNA recombinase complex; IPI:ZFIN.
DR GO; GO:1905347; C:endodeoxyribonuclease complex; IPI:ZFIN.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:ZFIN.
DR GO; GO:0046872; F:metal ion binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IPI:ZFIN.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IBA:GO_Central.
DR GO; GO:0030183; P:B cell differentiation; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0010390; P:histone monoubiquitination; ISS:UniProtKB.
DR GO; GO:0065004; P:protein-DNA complex assembly; IPI:ZFIN.
DR GO; GO:0002562; P:somatic diversification of immune receptors via germline recombination within a single locus; IMP:ZFIN.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
DR GO; GO:0033151; P:V(D)J recombination; IPI:ZFIN.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR024627; RAG1.
DR InterPro; IPR035714; RAG1_imp-bd.
DR InterPro; IPR019485; RAG1_Znf.
DR InterPro; IPR023336; RAG_nonamer-bd_dom.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR11539; PTHR11539; 1.
DR Pfam; PF12940; RAG1; 1.
DR Pfam; PF12560; RAG1_imp_bd; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS51487; NBD; 1.
DR PROSITE; PS51765; ZF_RAG1; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromatin regulator; DNA recombination; DNA-binding;
KW Endonuclease; Hydrolase; Metal-binding; Multifunctional enzyme; Nuclease;
KW Nucleus; Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..1057
FT /note="V(D)J recombination-activating protein 1"
FT /id="PRO_0000056009"
FT ZN_FING 296..335
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 357..386
FT /note="RAG1-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT DNA_BIND 408..475
FT /note="NBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00820"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 39..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 272
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 299
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 301
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 311
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 313
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 316
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 319
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 331
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 334
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 361
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 366
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 382
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01101"
FT BINDING 620
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 730
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 984
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT SITE 915
FT /note="Essential for DNA hairpin formation, participates in
FT base-stacking interactions near the cleavage site"
FT /evidence="ECO:0000250"
FT CONFLICT 895
FT /note="E -> A (in Ref. 2; AAA62611)"
FT /evidence="ECO:0000305"
FT TURN 415..417
FT /evidence="ECO:0007829|PDB:6DBI"
FT HELIX 421..425
FT /evidence="ECO:0007829|PDB:6DBI"
FT HELIX 428..441
FT /evidence="ECO:0007829|PDB:6DBI"
FT HELIX 446..458
FT /evidence="ECO:0007829|PDB:6DBI"
FT HELIX 464..471
FT /evidence="ECO:0007829|PDB:6DBI"
FT STRAND 472..477
FT /evidence="ECO:0007829|PDB:6DBI"
FT STRAND 479..481
FT /evidence="ECO:0007829|PDB:6DBI"
FT HELIX 483..492
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 497..509
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 510..513
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 519..526
FT /evidence="ECO:0007829|PDB:6DBJ"
FT TURN 527..529
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 530..532
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 537..540
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 564..566
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 573..576
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 578..588
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 590..599
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 604..606
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 611..622
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 630..632
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 639..651
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 655..658
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 660..664
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 671..673
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 675..680
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 687..704
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 707..713
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 716..728
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 731..737
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 743..747
FT /evidence="ECO:0007829|PDB:6DBJ"
FT STRAND 750..752
FT /evidence="ECO:0007829|PDB:3JBX"
FT HELIX 758..761
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 772..784
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 791..798
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 815..834
FT /evidence="ECO:0007829|PDB:6DBJ"
FT TURN 835..839
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 845..861
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 873..879
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 882..889
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 895..909
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 912..916
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 920..923
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 925..929
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 931..945
FT /evidence="ECO:0007829|PDB:6DBJ"
FT TURN 946..949
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 956..963
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 965..972
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 976..978
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 981..996
FT /evidence="ECO:0007829|PDB:6DBJ"
FT TURN 1002..1004
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 1005..1016
FT /evidence="ECO:0007829|PDB:6DBJ"
FT HELIX 1019..1026
FT /evidence="ECO:0007829|PDB:6DBJ"
FT TURN 1027..1029
FT /evidence="ECO:0007829|PDB:6DBJ"
SQ SEQUENCE 1057 AA; 121247 MW; 8769AD51329A92AF CRC64;
MEKGRWSSED APRASMPDEL SHPKFSEWKF KLFRVRSMEK APVQNETPVE KENQPELAME
KTSSQGSVMR LCFGGKSKEN VESARGRVDL KLQEIDTHMN LLKNMCRLCG IAIQKAKGPS
HEVQGVLEES SRCALRRMGC KLVTWPEVIL KVFKVDVTTD METVHPSLFC HRCWTAAIRG
GGFCSFTNTR IPDWKPHTSQ CNLCFPKKSS FQRVGRKRTK PLKSAHILPK RFRRDSSESS
RVWRQTTENP DGKEWLKLSV QRGQWVKNIT RCQRDHLSTK LIPTEVPADL IRAVTCQVCD
HLLSDPVQSP CRHLFCRLCI IRYTHALGPN CPTCNQHLNP SHLIKPAKFF LATLSSLPLL
CPSEECSDWV RLDSFREHCL NHYREKESQE EQTPSEQNLD GYLPVNKGGR PRQHLLSLTR
RAQKHRLRDL KNQVKTFAEK EEGGDVKSVC LTLFLLALRA GNEHKQADEL EAMMQGRGFG
LHPAVCLAIR VNTFLSCSQY HKMYRTVKAT SGRQIFQPLH TLRNAEKELL PGFHQFEWQP
ALKNVSTSWD VGIIDGLSGW TVSVDDVPAD TISRRFRYDV ALVSALKDLE EDIMEGLRER
ALDDSMCTSG FTVVVKESCD GMGDVSEKHG SGPAVPEKAV RFSFTIMSIS IRLEGEDDGI
TIFQEQKPNS ELSCRPLCLM FVDESDHETL TAILGPVVAE RKAMMESRLI ISVGGLLRSF
RFFFRGTGYD EKMVREMEGL EASGSTYICT LCDSTRAEAS QNMVLHSITR SHDENLERYE
IWRKNPFSES ADELRDRVKG VSAKPFMETQ PTLDALHCDI GNATEFYKIF QDEIGEVYQK
PNPSREERRR WRSTLDKQLR KKMKLKPVMR MNGNYARRLM TREAVEAVCE LVPSEERREA
LLKLMDLYLQ MKPVWRSTCP SRDCPDQLCQ YSYNSQQFAD LLSSMFKYRY DGKITNYLHK
TLAHVPEIVE RDGSIGAWAS EGNESGNKLF RRFRKMNARQ SKTFELEDIL KHHWLYTSKY
LQKFMEAHKN SVKAMQATFN PEETPEEADN SLDVPDF
