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P55895

- RAG2_HUMAN

UniProt

P55895 - RAG2_HUMAN

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Protein

V(D)J recombination-activating protein 2

Gene

RAG2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Core 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. DNA cleavage by the RAG complex 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 the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi419 – 4191Zinc 1By similarity
Metal bindingi423 – 4231Zinc 1By similarity
Metal bindingi446 – 4461Zinc 2By similarity
Metal bindingi452 – 4521Zinc 2By similarity
Metal bindingi455 – 4551Zinc 1By similarity
Metal bindingi458 – 4581Zinc 1By similarity
Metal bindingi478 – 4781Zinc 2By similarity
Metal bindingi481 – 4811Zinc 2By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri416 – 48469PHD-type; atypicalAdd
BLAST

GO - Molecular functioni

  1. chromatin binding Source: UniProtKB
  2. DNA binding Source: InterPro
  3. methylated histone binding Source: UniProtKB
  4. phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
  5. phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
  6. phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
  7. phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  8. phosphatidylinositol binding Source: UniProtKB
  9. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. B cell differentiation Source: UniProtKB
  2. chromatin modification Source: UniProtKB-KW
  3. pre-B cell allelic exclusion Source: UniProtKB
  4. T cell differentiation in thymus Source: UniProtKB
  5. V(D)J recombination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator

Keywords - Biological processi

DNA recombination

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
V(D)J recombination-activating protein 2
Short name:
RAG-2
Gene namesi
Name:RAG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:9832. RAG2.

Subcellular locationi

Nucleus By similarity

GO - Cellular componenti

  1. nucleus Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti77 – 771T → N in CHIDG; reduced recombination activity. 1 Publication
VAR_045960
Natural varianti451 – 4511G → A in CHIDG; reduced recombination activity. 1 Publication
VAR_045962
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti229 – 2291R → Q in T(-)B(-)NK(+) SCID. 1 Publication
VAR_005570
Natural varianti478 – 4781C → Y in T(-)B(-)NK(+) SCID. 1 Publication
VAR_005571
Omenn syndrome (OS) [MIM:603554]: Severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T-cells, hypereosinophilia, and high IgE levels.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411C → W in OS. 1 Publication
VAR_008895
Natural varianti285 – 2851M → R in OS. 1 Publication
VAR_008896

Keywords - Diseasei

Disease mutation, SCID

Organism-specific databases

MIMi233650. phenotype.
601457. phenotype.
603554. phenotype.
Orphaneti157949. Combined immunodeficiency with skin granulomas.
39041. Omenn syndrome.
331206. Severe combined immunodeficiency due to complete RAG1/2 deficiency.
PharmGKBiPA34186.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 527527V(D)J recombination-activating protein 2PRO_0000167137Add
BLAST

Proteomic databases

MaxQBiP55895.
PaxDbiP55895.
PRIDEiP55895.

PTM databases

PhosphoSiteiP55895.

Expressioni

Tissue specificityi

Cells of the B- and T-lymphocyte lineages.

Gene expression databases

BgeeiP55895.
CleanExiHS_RAG2.
ExpressionAtlasiP55895. baseline and differential.
GenevestigatoriP55895.

Interactioni

Subunit structurei

Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2.By similarity

Protein-protein interaction databases

BioGridi111833. 6 interactions.
STRINGi9606.ENSP00000308620.

Structurei

3D structure databases

ProteinModelPortaliP55895.
SMRiP55895. Positions 414-486.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3) (By similarity).By similarity

Sequence similaritiesi

Belongs to the RAG2 family.Curated
Contains 1 PHD-type zinc finger.Curated

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri416 – 48469PHD-type; atypicalAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG39310.
GeneTreeiENSGT00390000012559.
HOGENOMiHOG000237346.
HOVERGENiHBG006694.
InParanoidiP55895.
KOiK10988.
OMAiFGQKGWP.
OrthoDBiEOG73804B.
PhylomeDBiP55895.
TreeFamiTF331236.

Family and domain databases

Gene3Di2.120.10.80. 1 hit.
InterProiIPR011043. Gal_Oxase/kelch_b-propeller.
IPR015915. Kelch-typ_b-propeller.
IPR004321. RAG2.
IPR025162. RAG2_PHD.
IPR011011. Znf_FYVE_PHD.
[Graphical view]
PANTHERiPTHR10960. PTHR10960. 1 hit.
PfamiPF03089. RAG2. 1 hit.
PF13341. RAG2_PHD. 1 hit.
[Graphical view]
SUPFAMiSSF50965. SSF50965. 1 hit.
SSF57903. SSF57903. 1 hit.

Sequencei

Sequence statusi: Complete.

P55895-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSLQMVTVSN NIALIQPGFS LMNFDGQVFF FGQKGWPKRS CPTGVFHLDV
60 70 80 90 100
KHNHVKLKPT IFSKDSCYLP PLRYPATCTF KGSLESEKHQ YIIHGGKTPN
110 120 130 140 150
NEVSDKIYVM SIVCKNNKKV TFRCTEKDLV GDVPEARYGH SINVVYSRGK
160 170 180 190 200
SMGVLFGGRS YMPSTHRTTE KWNSVADCLP CVFLVDFEFG CATSYILPEL
210 220 230 240 250
QDGLSFHVSI AKNDTIYILG GHSLANNIRP ANLYRIRVDL PLGSPAVNCT
260 270 280 290 300
VLPGGISVSS AILTQTNNDE FVIVGGYQLE NQKRMICNII SLEDNKIEIR
310 320 330 340 350
EMETPDWTPD IKHSKIWFGS NMGNGTVFLG IPGDNKQVVS EGFYFYMLKC
360 370 380 390 400
AEDDTNEEQT TFTNSQTSTE DPGDSTPFED SEEFCFSAEA NSFDGDDEFD
410 420 430 440 450
TYNEDDEEDE SETGYWITCC PTCDVDINTW VPFYSTELNK PAMIYCSHGD
460 470 480 490 500
GHWVHAQCMD LAERTLIHLS AGSNKYYCNE HVEIARALHT PQRVLPLKKP
510 520
PMKSLRKKGS GKILTPAKKS FLRRLFD
Length:527
Mass (Da):59,241
Last modified:November 1, 1997 - v1
Checksum:i1CC4D0F88635BA87
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti154 – 1541V → A in AAH22397. (PubMed:15489334)Curated
Sequence conflicti322 – 3221M → T in AAH22397. (PubMed:15489334)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411C → W in OS. 1 Publication
VAR_008895
Natural varianti77 – 771T → N in CHIDG; reduced recombination activity. 1 Publication
VAR_045960
Natural varianti229 – 2291R → Q in T(-)B(-)NK(+) SCID. 1 Publication
VAR_005570
Natural varianti285 – 2851M → R in OS. 1 Publication
VAR_008896
Natural varianti293 – 2931E → G.
Corresponds to variant rs16929093 [ dbSNP | Ensembl ].
VAR_045961
Natural varianti451 – 4511G → A in CHIDG; reduced recombination activity. 1 Publication
VAR_045962
Natural varianti478 – 4781C → Y in T(-)B(-)NK(+) SCID. 1 Publication
VAR_005571

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M94633 Genomic DNA. No translation available.
AK292664 mRNA. Translation: BAF85353.1.
CH471064 Genomic DNA. Translation: EAW68117.1.
BC022397 mRNA. Translation: AAH22397.1.
CCDSiCCDS7903.1.
RefSeqiNP_000527.2. NM_000536.3.
NP_001230714.1. NM_001243785.1.
NP_001230715.1. NM_001243786.1.
UniGeneiHs.714519.

Genome annotation databases

EnsembliENST00000311485; ENSP00000308620; ENSG00000175097.
ENST00000618712; ENSP00000478672; ENSG00000175097.
GeneIDi5897.
KEGGihsa:5897.
UCSCiuc001mwv.4. human.

Polymorphism databases

DMDMi2498830.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

RAG2base

RAG2 deficiency database

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M94633 Genomic DNA. No translation available.
AK292664 mRNA. Translation: BAF85353.1 .
CH471064 Genomic DNA. Translation: EAW68117.1 .
BC022397 mRNA. Translation: AAH22397.1 .
CCDSi CCDS7903.1.
RefSeqi NP_000527.2. NM_000536.3.
NP_001230714.1. NM_001243785.1.
NP_001230715.1. NM_001243786.1.
UniGenei Hs.714519.

3D structure databases

ProteinModelPortali P55895.
SMRi P55895. Positions 414-486.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111833. 6 interactions.
STRINGi 9606.ENSP00000308620.

PTM databases

PhosphoSitei P55895.

Polymorphism databases

DMDMi 2498830.

Proteomic databases

MaxQBi P55895.
PaxDbi P55895.
PRIDEi P55895.

Protocols and materials databases

DNASUi 5897.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000311485 ; ENSP00000308620 ; ENSG00000175097 .
ENST00000618712 ; ENSP00000478672 ; ENSG00000175097 .
GeneIDi 5897.
KEGGi hsa:5897.
UCSCi uc001mwv.4. human.

Organism-specific databases

CTDi 5897.
GeneCardsi GC11M036613.
H-InvDB HIX0009568.
HGNCi HGNC:9832. RAG2.
MIMi 179616. gene.
233650. phenotype.
601457. phenotype.
603554. phenotype.
neXtProti NX_P55895.
Orphaneti 157949. Combined immunodeficiency with skin granulomas.
39041. Omenn syndrome.
331206. Severe combined immunodeficiency due to complete RAG1/2 deficiency.
PharmGKBi PA34186.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG39310.
GeneTreei ENSGT00390000012559.
HOGENOMi HOG000237346.
HOVERGENi HBG006694.
InParanoidi P55895.
KOi K10988.
OMAi FGQKGWP.
OrthoDBi EOG73804B.
PhylomeDBi P55895.
TreeFami TF331236.

Miscellaneous databases

GenomeRNAii 5897.
NextBioi 22938.
PROi P55895.
SOURCEi Search...

Gene expression databases

Bgeei P55895.
CleanExi HS_RAG2.
ExpressionAtlasi P55895. baseline and differential.
Genevestigatori P55895.

Family and domain databases

Gene3Di 2.120.10.80. 1 hit.
InterProi IPR011043. Gal_Oxase/kelch_b-propeller.
IPR015915. Kelch-typ_b-propeller.
IPR004321. RAG2.
IPR025162. RAG2_PHD.
IPR011011. Znf_FYVE_PHD.
[Graphical view ]
PANTHERi PTHR10960. PTHR10960. 1 hit.
Pfami PF03089. RAG2. 1 hit.
PF13341. RAG2_PHD. 1 hit.
[Graphical view ]
SUPFAMi SSF50965. SSF50965. 1 hit.
SSF57903. SSF57903. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence and chromosome assignment to 11p13-p12 of human RAG genes."
    Ichihara Y., Hirai M., Kurosawa Y.
    Immunol. Lett. 33:277-284(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Placenta.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Thymus.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  5. "Expression of human recombination activating genes (RAG1 and RAG2) in neoplastic lymphoid cells: correlation with cell differentiation and antigen receptor expression."
    Bories J.C., Cayuela J.-M., Loiseau P., Sigaux F.
    Blood 78:2053-2061(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 318-411.
  6. Cited for: VARIANTS T(-)B(-)NK(+) SCID GLN-229 AND TYR-478.
  7. Cited for: VARIANTS OS TRP-41 AND ARG-285.
  8. Cited for: VARIANTS CHIDG ASN-77 AND ALA-451, CHARACTERIZATION OF VARIANTS CHIDG ASN-77 AND ALA-451.

Entry informationi

Entry nameiRAG2_HUMAN
AccessioniPrimary (citable) accession number: P55895
Secondary accession number(s): A8K9E9, Q8TBL4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: October 29, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3