RAG2

Protein identityUniProt · HPA

UniProt accession

P55895

Gene

RAG2

Ensembl

ENSG00000175097

Chromosome

11

Canonical length

527 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

This gene encodes a protein that is involved in the initiation of V(D)J recombination during B and T cell development. This protein forms a complex with the product of the adjacent recombination activating gene 1, and this complex can form double-strand breaks by cleaving DNA at conserved recombination signal sequences. The recombination activating gene 1 component is thought to contain most of the catalytic activity, while the N-terminal of the recombination activating gene 2 component is thought to form a six-bladed propeller in the active core that serves as a binding scaffold for the tight association of the complex with DNA. A C-terminal plant homeodomain finger-like motif in this protein is necessary for interactions with chromatin components, specifically with histone H3 that is trimethylated at lysine 4. Mutations in this gene cause Omenn syndrome, a form of severe combined immunodeficiency associated with autoimmune-like symptoms. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

527 residues, UniProt reviewed canonical sequence.

>P55895|RAG2
     1  MSLQMVTVSN NIALIQPGFS LMNFDGQVFF FGQKGWPKRS CPTGVFHLDV KHNHVKLKPT
    61  IFSKDSCYLP PLRYPATCTF KGSLESEKHQ YIIHGGKTPN NEVSDKIYVM SIVCKNNKKV
   121  TFRCTEKDLV GDVPEARYGH SINVVYSRGK SMGVLFGGRS YMPSTHRTTE KWNSVADCLP
   181  CVFLVDFEFG CATSYILPEL QDGLSFHVSI AKNDTIYILG GHSLANNIRP ANLYRIRVDL
   241  PLGSPAVNCT VLPGGISVSS AILTQTNNDE FVIVGGYQLE NQKRMICNII SLEDNKIEIR
   301  EMETPDWTPD IKHSKIWFGS NMGNGTVFLG IPGDNKQVVS EGFYFYMLKC AEDDTNEEQT
   361  TFTNSQTSTE DPGDSTPFED SEEFCFSAEA NSFDGDDEFD TYNEDDEEDE SETGYWITCC
   421  PTCDVDINTW VPFYSTELNK PAMIYCSHGD GHWVHAQCMD LAERTLIHLS AGSNKYYCNE
   481  HVEIARALHT PQRVLPLKKP PMKSLRKKGS GKILTPAKKS FLRRLFD

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RAG2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.34

Highest tissue expression

140 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RAG2.

Disease | AllUniProt

Conditions RAG2 is implicated in, by any mechanism.

• Combined cellular and humoral immune defects with granulomas (CHIDG) MIM:233650
• Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive (T(-)B(-)NK(+) SCID) MIM:601457
• Omenn syndrome (OS) MIM:603554

Disease | GeneticClinVar

146 pathogenic / likely-pathogenic of 628 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Combined immunodeficiency with skin granulomas
• Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
• Histiocytic medullary reticulosis
• Recombinase activating gene 2 deficiency
• Inborn error of immunity

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.79

gnomAD pLI

0.02

gnomAD missense Z

0.2

DepMap mean gene effect

-0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• B cell differentiation
• B cell homeostatic proliferation
• B cell lineage commitment
• defense response to bacterium
• DN2 thymocyte differentiation
• mature B cell differentiation involved in immune response
• negative regulation of T cell differentiation in thymus
• organ growth
• positive regulation of organ growth
• pre-B cell allelic exclusion
• T cell differentiation in thymus
• T cell lineage commitment
• V(D)J recombination

Molecular functions

• chromatin binding
• histone H3K4me3 reader activity
• phosphatidylinositol binding
• phosphatidylinositol-3,4,5-trisphosphate binding
• phosphatidylinositol-3,4-bisphosphate binding
• phosphatidylinositol-3,5-bisphosphate binding
• phosphatidylinositol-4,5-bisphosphate binding
• sequence-specific DNA binding
• zinc ion binding

Cellular components

• DNA recombinase complex
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Zinc finger, FYVE/PHD-type
• Galactose oxidase/kelch, beta-propeller
• Kelch-type beta-propeller
• V-D-J recombination activating protein 2
• Recombination activating protein 2, PHD domain
• Recombination activating protein 2
• RAG2 PHD domain

KeywordsUniProt

• Chromatin regulator
• DNA recombination
• Metal-binding
• Nucleus
• SCID
• Zinc
• Zinc-finger