P15918 (RAG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
V(D)J recombination-activating protein 1
Short name=RAG-1

Alternative name(s):
RING finger protein 74

Including the following 2 domains:

1. Endonuclease RAG1
   EC=3.1.-.-
2. E3 ubiquitin-protein ligase RAG1
   EC=6.3.2.-

Gene names

Name:	RAG1
Synonyms:	RNF74

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1043 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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 structure	Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 By similarity.
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. Ref.4 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. Ref.4
Post-translational modification	Autoubiquitinated in the presence of CDC34/UBCH3 By similarity.
Involvement in disease	Combined cellular and humoral immune defects with granulomas (CHIDG) [MIM:233650]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6 Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Omenn syndrome (OS) [MIM:603554]: Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.12 Ref.14 Ref.15 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. Note: The disease is caused by mutations affecting the gene represented in this entry.
Sequence similarities	Belongs to the RAG1 family. Contains 1 NBD (nonamer binding) DNA-binding domain. Contains 1 RAG1-type zinc finger. Contains 1 RING-type zinc finger.
Sequence caution	The sequence AAM77798.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	DNA recombination Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation SCID
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Chromatin regulator Endonuclease Hydrolase Ligase Nuclease
PTM	Isopeptide bond Ubl conjugation
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	T cell differentiation in thymus Inferred from sequence or structural similarity. Source: UniProtKB V(D)J recombination Inferred from sequence or structural similarity. Source: UniProtKB histone monoubiquitination Inferred from sequence or structural similarity. Source: UniProtKB immune response Traceable author statement Ref.7. Source: ProtInc negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of thymocyte apoptotic process Inferred from electronic annotation. Source: Compara pre-B cell allelic exclusion Inferred from sequence or structural similarity. Source: UniProtKB protein autoubiquitination Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	endonuclease activity Inferred from sequence or structural similarity. Source: UniProtKB histone binding Inferred from sequence or structural similarity. Source: UniProtKB protein homodimerization activity Inferred from sequence or structural similarity. Source: UniProtKB sequence-specific DNA binding Inferred from sequence or structural similarity. Source: UniProtKB ubiquitin-protein ligase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1755109,EBI-389883

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1043	1043	V(D)J recombination-activating protein 1		PRO_0000056004
Regions
	Zinc finger	293 – 332	40	RING-type
	Zinc finger	354 – 383	30	RAG1-type
	DNA binding	392 – 459	68	NBD
	Region	1 – 288	288	Interaction with importin alpha-1
Sites
	Metal binding	269	1	Zinc 1 By similarity
	Metal binding	273	1	Zinc 1 By similarity
	Metal binding	293	1	Zinc 2 By similarity
	Metal binding	296	1	Zinc 1 By similarity
	Metal binding	296	1	Zinc 2 By similarity
	Metal binding	298	1	Zinc 1 By similarity
	Metal binding	308	1	Zinc 3 By similarity
	Metal binding	310	1	Zinc 3 By similarity
	Metal binding	313	1	Zinc 2 By similarity
	Metal binding	316	1	Zinc 2 By similarity
	Metal binding	328	1	Zinc 3 By similarity
	Metal binding	331	1	Zinc 3 By similarity
	Metal binding	358	1	Zinc 4 By similarity
	Metal binding	363	1	Zinc 4 By similarity
	Metal binding	375	1	Zinc 4 By similarity
	Metal binding	379	1	Zinc 4 By similarity
	Metal binding	603	1	Divalent metal cation; catalytic By similarity
	Metal binding	711	1	Divalent metal cation; catalytic By similarity
	Metal binding	965	1	Divalent metal cation; catalytic By similarity
	Site	896	1	Essential for DNA hairpin formation, participates in base-stacking interactions near the cleavage site By similarity
Amino acid modifications
	Cross-link	234		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Natural variant	156	1	A → V. Ref.6 Corresponds to variant rs1801203 [ dbSNP | Ensembl ].		VAR_007800
	Natural variant	169	1	S → L. Corresponds to variant rs4151027 [ dbSNP | Ensembl ].		VAR_029260
	Natural variant	244	1	R → G. Ref.5 Corresponds to variant rs199474683 [ dbSNP | Ensembl ].		VAR_007801
	Natural variant	247	1	R → H. Corresponds to variant rs4151029 [ dbSNP | Ensembl ].		VAR_029261
	Natural variant	249	1	H → R. Ref.1 Ref.5 Corresponds to variant rs3740955 [ dbSNP | Ensembl ].		VAR_007802
	Natural variant	302	1	D → E. Corresponds to variant rs4151030 [ dbSNP | Ensembl ].		VAR_020113
	Natural variant	314	1	R → W in CHIDG; reduced recombination activity. Ref.11 Corresponds to variant rs121918568 [ dbSNP | Ensembl ].		VAR_045957
	Natural variant	328	1	C → Y in OS. Ref.9 Corresponds to variant rs121918571 [ dbSNP | Ensembl ].		VAR_025971
	Natural variant	396	1	R → C in OS. Ref.7 Ref.8 Corresponds to variant rs104894289 [ dbSNP | Ensembl ].		VAR_008886
	Natural variant	396	1	R → H in OS. Ref.7 Ref.12 Corresponds to variant rs104894291 [ dbSNP | Ensembl ].		VAR_008887
	Natural variant	396	1	R → L in OS. Ref.9 Corresponds to variant rs104894291 [ dbSNP | Ensembl ].		VAR_025972
	Natural variant	401	1	S → P in OS. Ref.9 Ref.12 Corresponds to variant rs199474682 [ dbSNP | Ensembl ].		VAR_025973
	Natural variant	410	1	R → Q in OS/T(-)B(-)NK(+) SCID; atypical. Ref.9 Corresponds to variant rs199474684 [ dbSNP | Ensembl ].		VAR_025974
	Natural variant	429	1	D → G in OS. Ref.7 Corresponds to variant rs104894292 [ dbSNP | Ensembl ].		VAR_008888
	Natural variant	433	1	V → M in T(-)B(-)NK(+) SCID and OS/T(-)B(-)NK(+) SCID; atypical. Ref.9 Ref.12 Corresponds to variant rs199474679 [ dbSNP | Ensembl ].		VAR_025975
	Natural variant	435	1	M → V in OS. Ref.9 Corresponds to variant rs141524540 [ dbSNP | Ensembl ].		VAR_025976
	Natural variant	444	1	A → V in OS/T(-)B(-)NK(+) SCID; atypical. Ref.9 Corresponds to variant rs199474685 [ dbSNP | Ensembl ].		VAR_025977
	Natural variant	449	1	R → K. Corresponds to variant rs4151031 [ dbSNP | Ensembl ].		VAR_029262
	Natural variant	454	1	L → Q in OS. Ref.14 Corresponds to variant rs199474677 [ dbSNP | Ensembl ].		VAR_067274
	Natural variant	474	1	R → C Probable disease-associated mutation found in a patient with relatively late onset of infections and isolated T-cell lymphopenia. Ref.13 Corresponds to variant rs199474678 [ dbSNP | Ensembl ].		VAR_067275
	Natural variant	474	1	R → H in OS/T(-)B(-)NK(+) SCID; atypical. Ref.9 Corresponds to variant rs199474686 [ dbSNP | Ensembl ].		VAR_025978
	Natural variant	507	1	R → W in OS/T(-)B(-)NK(+) SCID and CHIDG; atypical; reduced recombination activity when associated with H-737. Ref.9 Ref.11 Corresponds to variant rs104894298 [ dbSNP | Ensembl ].		VAR_025979
	Natural variant	522	1	W → C in OS/T(-)B(-)NK(+) SCID; atypical. Ref.9 Corresponds to variant rs193922461 [ dbSNP | Ensembl ].		VAR_025980
	Natural variant	525	1	P → S. Corresponds to variant rs4151032 [ dbSNP | Ensembl ].		VAR_029263
	Natural variant	559	1	R → S in T(-)B(-)NK(+) SCID and OS. Ref.9 Ref.12 Corresponds to variant rs199474681 [ dbSNP | Ensembl ].		VAR_025981
	Natural variant	561	1	R → C in OS. Ref.7 Corresponds to variant rs104894285 [ dbSNP | Ensembl ].		VAR_008890
	Natural variant	561	1	R → H in OS. Ref.7 Corresponds to variant rs104894284 [ dbSNP | Ensembl ].		VAR_008889
	Natural variant	624	1	R → C in OS. Ref.9 Corresponds to variant rs199474688 [ dbSNP | Ensembl ].		VAR_025982
	Natural variant	624	1	R → H in T(-)B(-)NK(+) SCID. Ref.6 Ref.12 Corresponds to variant rs199474680 [ dbSNP | Ensembl ].		VAR_007803
	Natural variant	669	1	E → G in OS. Ref.9 Corresponds to variant rs199474689 [ dbSNP | Ensembl ].		VAR_025983
	Natural variant	699	1	R → W in OS; also in a patient with multiple autoimmune disorders. Ref.15 Corresponds to variant rs199474676 [ dbSNP | Ensembl ].		VAR_067276
	Natural variant	722	1	E → K in T(-)B(-)NK(+) SCID. Ref.6 Corresponds to variant rs28933392 [ dbSNP | Ensembl ].		VAR_007804
	Natural variant	737	1	R → H in OS and CHIDG; reduced recombination activity when associated with T-507. Ref.7 Ref.11 Corresponds to variant rs104894286 [ dbSNP | Ensembl ].		VAR_008891
	Natural variant	753	1	H → L in OS/T(-)B(-)NK(+) SCID; atypical. Ref.9 Corresponds to variant rs199474687 [ dbSNP | Ensembl ].		VAR_025984
	Natural variant	778	1	R → Q in CHIDG; reduced recombination activity. Ref.11 Corresponds to variant rs121918569 [ dbSNP | Ensembl ].		VAR_045958
	Natural variant	820	1	K → R. Corresponds to variant rs2227973 [ dbSNP | Ensembl ].		VAR_008892
	Natural variant	841	1	R → W in T-CMVA; also found in a patient with an atypical form of severe combined immunodeficiency /Omenn syndrome. Ref.10 Corresponds to variant rs104894287 [ dbSNP | Ensembl ].		VAR_025985
	Natural variant	855	1	N → I in immunodeficiency; severe combined. Ref.9 Corresponds to variant rs199474690 [ dbSNP | Ensembl ].		VAR_025986
	Natural variant	880	1	E → K. Corresponds to variant rs4151033 [ dbSNP | Ensembl ].		VAR_020114
	Natural variant	885	1	L → R in OS. Ref.8 Corresponds to variant rs199474691 [ dbSNP | Ensembl ].		VAR_008893
	Natural variant	887	1	D → N. Corresponds to variant rs4151034 [ dbSNP | Ensembl ].		VAR_029264
	Natural variant	912	1	Y → C in OS. Ref.7 Corresponds to variant rs104894290 [ dbSNP | Ensembl ].		VAR_008894
	Natural variant	975	1	R → Q in OS. Ref.9 Corresponds to variant rs150739647 [ dbSNP | Ensembl ].		VAR_025987
	Natural variant	975	1	R → W in CHIDG; reduced recombination activity. Ref.11 Corresponds to variant rs121918570 [ dbSNP | Ensembl ].		VAR_045959
	Natural variant	981	1	Q → P in T-CMVA. Ref.10 Corresponds to variant rs104894288 [ dbSNP | Ensembl ].		VAR_025988

Sequences

	Sequence		Length	Mass (Da)
	P15918 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: 5417A7413DA8CB65	FASTA	1,043	119,097
	10 20 30 40 50 60 MAASFPPTLG LSSAPDEIQH PHIKFSEWKF KLFRVRSFEK TPEEAQKEKK DSFEGKPSLE 70 80 90 100 110 120 QSPAVLDKAD GQKPVPTQPL LKAHPKFSKK FHDNEKARGK AIHQANLRHL CRICGNSFRA 130 140 150 160 170 180 DEHNRRYPVH GPVDGKTLGL LRKKEKRATS WPDLIAKVFR IDVKADVDSI HPTEFCHNCW 190 200 210 220 230 240 SIMHRKFSSA PCEVYFPRNV TMEWHPHTPS CDICNTARRG LKRKSLQPNL QLSKKLKTVL 250 260 270 280 290 300 DQARQARQHK RRAQARISSK DVMKKIANCS KIHLSTKLLA VDFPEHFVKS ISCQICEHIL 310 320 330 340 350 360 ADPVETNCKH VFCRVCILRC LKVMGSYCPS CRYPCFPTDL ESPVKSFLSV LNSLMVKCPA 370 380 390 400 410 420 KECNEEVSLE KYNHHISSHK ESKEIFVHIN KGGRPRQHLL SLTRRAQKHR LRELKLQVKA 430 440 450 460 470 480 FADKEEGGDV KSVCMTLFLL ALRARNEHRQ ADELEAIMQG KGSGLQPAVC LAIRVNTFLS 490 500 510 520 530 540 CSQYHKMYRT VKAITGRQIF QPLHALRNAE KVLLPGYHHF EWQPPLKNVS SSTDVGIIDG 550 560 570 580 590 600 LSGLSSSVDD YPVDTIAKRF RYDSALVSAL MDMEEDILEG MRSQDLDDYL NGPFTVVVKE 610 620 630 640 650 660 SCDGMGDVSE KHGSGPVVPE KAVRFSFTIM KITIAHSSQN VKVFEEAKPN SELCCKPLCL 670 680 690 700 710 720 MLADESDHET LTAILSPLIA EREAMKSSEL MLELGGILRT FKFIFRGTGY DEKLVREVEG 730 740 750 760 770 780 LEASGSVYIC TLCDATRLEA SQNLVFHSIT RSHAENLERY EVWRSNPYHE SVEELRDRVK 790 800 810 820 830 840 GVSAKPFIET VPSIDALHCD IGNAAEFYKI FQLEIGEVYK NPNASKEERK RWQATLDKHL 850 860 870 880 890 900 RKKMNLKPIM RMNGNFARKL MTKETVDAVC ELIPSEERHE ALRELMDLYL KMKPVWRSSC 910 920 930 940 950 960 PAKECPESLC QYSFNSQRFA ELLSTKFKYR YEGKITNYFH KTLAHVPEII ERDGSIGAWA 970 980 990 1000 1010 1020 SEGNESGNKL FRRFRKMNAR QSKCYEMEDV LKHHWLYTSK YLQKFMNAHN ALKTSGFTMN 1030 1040 PQASLGDPLG IEDSLESQDS MEF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The V(D)J recombination activating gene, RAG-1." Schatz D.G., Oettinger M.A., Baltimore D. Cell 59:1035-1048(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ARG-249.
[2]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"RAG-1 interacts with the repeated amino acid motif of the human homologue of the yeast protein SRP1." Cortes P., Ye Z.-S., Baltimore D. Proc. Natl. Acad. Sci. U.S.A. 91:7633-7637(1994) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF IMPORTIN ALPHA-1 BINDING DOMAIN.
[5]	"Two new variants of RAG-1 protein predicted by SSCP." Nomdedeu J.F., Lasa A., Seminago R., Rubiol E., Baiget M., Soler J. Hum. Mutat. 8:191-192(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GLY-244 AND ARG-249.
[6]	"RAG mutations in human B cell-negative SCID." Schwarz K., Gauss G.H., Ludwig L., Pannicke U., Li Z., Linder D., Friedrich W., Seger R.A., Hansen-Hagge T.E., Desiderio S., Lieber M.R., Bartram C.R. Science 274:97-99(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS T(-)B(-)NK(+) SCID HIS-624 AND LYS-722, VARIANT VAL-156.
[7]	"Partial V(D)J recombination activity leads to Omenn syndrome." Villa A., Santagata S., Bozzi F., Giliani S., Frattini A., Imberti L., Gatta L.B., Ochs H.D., Schwarz K., Notarangelo L.D., Vezzoni P., Spanopoulou E. Cell 93:885-896(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OS CYS-396; HIS-396; GLY-429; HIS-561; CYS-561; HIS-737 AND CYS-912.
[8]	"Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders." Wada T., Takei K., Kudo M., Shimura S., Kasahara Y., Koizumi S., Kawa-Ha K., Ishida Y., Imashuku S., Seki H., Yachie A. Clin. Exp. Immunol. 119:148-155(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OS CYS-396 AND ARG-885.
[9]	"V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations." Villa A., Sobacchi C., Notarangelo L.D., Bozzi F., Abinun M., Abrahamsen T.G., Arkwright P.D., Baniyash M., Brooks E.G., Conley M.E., Cortes P., Duse M., Fasth A., Filipovich A.M., Infante A.J., Jones A., Mazzolari E., Muller S.M. , Pasic S., Rechavi G., Sacco M.G., Santagata S., Schroeder M.L., Seger R., Strina D., Ugazio A., Vaeliaho J., Vihinen M., Vogler L.B., Ochs H., Vezzoni P., Friedrich W., Schwarz K. Blood 97:81-88(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS OS TYR-328; LEU-396; PRO-401; VAL-435; SER-559; CYS-624; GLY-669 AND GLN-975, VARIANTS OS/T(-)B(-)NK(+) SCID GLN-410; MET-433; VAL-444; HIS-474; TRP-507; CYS-522 AND LEU-753, VARIANT IMMUNODEFICIENCY ILE-855.
[10]	"A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection." de Villartay J.-P., Lim A., Al-Mousa H., Dupont S., Dechanet-Merville J., Coumau-Gatbois E., Gougeon M.-L., Lemainque A., Eidenschenk C., Jouanguy E., Abel L., Casanova J.-L., Fischer A., Le Deist F. J. Clin. Invest. 115:3291-3299(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS T-CMVA TRP-841 AND PRO-981.
[11]	"An immunodeficiency disease with RAG mutations and granulomas." Schuetz C., Huck K., Gudowius S., Megahed M., Feyen O., Hubner B., Schneider D.T., Manfras B., Pannicke U., Willemze R., Knuechel R., Goebel U., Schulz A., Borkhardt A., Friedrich W., Schwarz K., Niehues T. N. Engl. J. Med. 358:2030-2038(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CHIDG TRP-314; TRP-507; HIS-737; GLN-778 AND TRP-975, CHARACTERIZATION OF VARIANTS CHIDG TRP-314; TRP-507; HIS-737; GLN-778 AND TRP-975.
[12]	"Molecular analysis of T-B-NK+ severe combined immunodeficiency and Omenn syndrome cases in Saudi Arabia." Alsmadi O., Al-Ghonaium A., Al-Muhsen S., Arnaout R., Al-Dhekri H., Al-Saud B., Al-Kayal F., Al-Saud H., Al-Mousa H. BMC Med. Genet. 10:116-116(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS T(-)B(-)NK(+) SCID MET-433; SER-559 AND HIS-624, VARIANTS OS HIS-396 AND PRO-401.
[13]	"Highly variable clinical phenotypes of hypomorphic RAG1 mutations." Avila E.M., Uzel G., Hsu A., Milner J.D., Turner M.L., Pittaluga S., Freeman A.F., Holland S.M. Pediatrics 126:E1248-E1252(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYS-474.
[14]	"Novel mutations in RAG1/2 and ADA genes in Israeli patients presenting with T-B-SCID or Omenn syndrome." Dalal I., Tasher D., Somech R., Etzioni A., Garti B.Z., Lev D., Cohen S., Somekh E., Leshinsky-Silver E. Clin. Immunol. 140:284-290(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OS GLN-454.
[15]	"Clinical characteristics and molecular analysis of three Chinese children with Omenn syndrome." Zhang Z.Y., Zhao X.D., Jiang L.P., Liu E.M., Cui Y.X., Wang M., Wei H., Yu J., An Y.F., Yang X.Q. Pediatr. Allergy Immunol. 22:482-487(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT OS TRP-699.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

RAG1base

RAG1 deficiency database

Mendelian genes recombination activating gene 1 (RAG1)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases
EMBL GenBank DDBJ	M29474 mRNA. Translation: AAA60248.1. AY130302 Genomic DNA. Translation: AAM77798.1. Sequence problems. AC139427 Genomic DNA. No translation available.
IPI	IPI00013914.
PIR	A33754.
RefSeq	NP_000439.1. NM_000448.2.
UniGene	Hs.677010. Hs.73958.
3D structure databases
ProteinModelPortal	P15918.
SMR	P15918. Positions 268-383, 392-459.
ModBase	Search...
Protein-protein interaction databases
IntAct	P15918. 5 interactions.
MINT	MINT-1511469.
STRING	9606.ENSP00000299440.
PTM databases
PhosphoSite	P15918.
Proteomic databases
PaxDb	P15918.
PRIDE	P15918.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000299440; ENSP00000299440; ENSG00000166349.
GeneID	5896.
KEGG	hsa:5896.
UCSC	uc001mwu.4. human.
Organism-specific databases
CTD	5896.
GeneCards	GC11P036546.
HGNC	HGNC:9831. RAG1.
MIM	179615. gene. 233650. phenotype. 601457. phenotype. 603554. phenotype. 609889. phenotype.
neXtProt	NX_P15918.
Orphanet	39041. Omenn syndrome. 157949. Primary immunodeficiency with skin granulomas. 231154. Severe combined immunodeficiency T+ B+ due to partial RAG1 deficiency. 275. Severe combined immunodeficiency, alymphocytotic type.
PharmGKB	PA34185.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG45367.
HOGENOM	HOG000232009.
HOVERGEN	HBG003861.
InParanoid	P15918.
KO	K10628.
OMA	CDGMGDV.
OrthoDB	EOG4PRSPZ.
PhylomeDB	P15918.
Gene expression databases
ArrayExpress	P15918.
Bgee	P15918.
CleanEx	HS_RAG1.
Genevestigator	P15918.
GermOnline	ENSG00000166349. Homo sapiens.
Family and domain databases
Gene3D	3.30.160.60. 1 hit. 3.30.40.10. 1 hit.
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. [Graphical view]
PANTHER	PTHR11539. PTHR11539. 1 hit.
Pfam	PF12940. RAG1. 1 hit. PF10426. zf-RAG1. 1 hit. [Graphical view]
SMART	SM00184. RING. 1 hit. SM00355. ZnF_C2H2. 2 hits. [Graphical view]
PROSITE	PS51487. NBD. 1 hit. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5896.
NextBio	22934.
SOURCE	Search...

Entry information

Entry name

RAG1_HUMAN

Accession

Primary (citable) accession number: P15918
Secondary accession number(s): Q8NER2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 152 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.