RAG1

Protein identityUniProt · HPA

UniProt accession

P15918

Gene

RAG1

Ensembl

ENSG00000166349

Chromosome

11

Canonical length

1043 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nucleoli

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is involved in activation of immunoglobulin V-D-J recombination. The encoded protein is involved in recognition of the DNA substrate, but stable binding and cleavage activity also requires RAG2. Defects in this gene can be the cause of several diseases. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

1043 residues, UniProt reviewed canonical sequence.

>P15918|RAG1
     1  MAASFPPTLG LSSAPDEIQH PHIKFSEWKF KLFRVRSFEK TPEEAQKEKK DSFEGKPSLE
    61  QSPAVLDKAD GQKPVPTQPL LKAHPKFSKK FHDNEKARGK AIHQANLRHL CRICGNSFRA
   121  DEHNRRYPVH GPVDGKTLGL LRKKEKRATS WPDLIAKVFR IDVKADVDSI HPTEFCHNCW
   181  SIMHRKFSSA PCEVYFPRNV TMEWHPHTPS CDICNTARRG LKRKSLQPNL QLSKKLKTVL
   241  DQARQARQHK RRAQARISSK DVMKKIANCS KIHLSTKLLA VDFPEHFVKS ISCQICEHIL
   301  ADPVETNCKH VFCRVCILRC LKVMGSYCPS CRYPCFPTDL ESPVKSFLSV LNSLMVKCPA
   361  KECNEEVSLE KYNHHISSHK ESKEIFVHIN KGGRPRQHLL SLTRRAQKHR LRELKLQVKA
   421  FADKEEGGDV KSVCMTLFLL ALRARNEHRQ ADELEAIMQG KGSGLQPAVC LAIRVNTFLS
   481  CSQYHKMYRT VKAITGRQIF QPLHALRNAE KVLLPGYHHF EWQPPLKNVS SSTDVGIIDG
   541  LSGLSSSVDD YPVDTIAKRF RYDSALVSAL MDMEEDILEG MRSQDLDDYL NGPFTVVVKE
   601  SCDGMGDVSE KHGSGPVVPE KAVRFSFTIM KITIAHSSQN VKVFEEAKPN SELCCKPLCL
   661  MLADESDHET LTAILSPLIA EREAMKSSEL MLELGGILRT FKFIFRGTGY DEKLVREVEG
   721  LEASGSVYIC TLCDATRLEA SQNLVFHSIT RSHAENLERY EVWRSNPYHE SVEELRDRVK
   781  GVSAKPFIET VPSIDALHCD IGNAAEFYKI FQLEIGEVYK NPNASKEERK RWQATLDKHL
   841  RKKMNLKPIM RMNGNFARKL MTKETVDAVC ELIPSEERHE ALRELMDLYL KMKPVWRSSC
   901  PAKECPESLC QYSFNSQRFA ELLSTKFKYR YEGKITNYFH KTLAHVPEII ERDGSIGAWA
   961  SEGNESGNKL FRRFRKMNAR QSKCYEMEDV LKHHWLYTSK YLQKFMNAHN ALKTSGFTMN
  1021  PQASLGDPLG IEDSLESQDS MEF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against RAG1 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)

0.35

Highest tissue expression

368 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about RAG1.

Disease | AllUniProt

Conditions RAG1 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
• Alpha/beta T-cell lymphopenia, with gamma/delta T-cell expansion, severe cytomegalovirus infection and autoimmunity (T-CMVA) MIM:609889

Disease | GeneticClinVar

173 pathogenic / likely-pathogenic of 949 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
• Combined immunodeficiency with skin granulomas
• Combined immunodeficiency due to partial RAG1 deficiency
• Histiocytic medullary reticulosis
• Severe combined immunodeficiency disease

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)

0.74

gnomAD pLI

0

gnomAD missense Z

0.58

DepMap mean gene effect

-0.07

DepMap dependency class

selective

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

• adaptive immune response
• B cell differentiation
• chromatin organization
• DNA recombination
• immune response
• negative regulation of thymocyte apoptotic process
• positive regulation of T cell differentiation
• pre-B cell allelic exclusion
• protein autoubiquitination
• regulation of behavioral fear response
• T cell differentiation in thymus
• T cell homeostasis
• thymus development
• V(D)J recombination
• visual learning

Molecular functions

• DNA binding
• endonuclease activity
• histone binding
• hydrolase activity
• metal ion binding
• protein homodimerization activity
• sequence-specific DNA binding
• ubiquitin protein ligase activity
• ubiquitin-protein transferase activity
• zinc ion binding

Cellular components

• DNA recombinase complex
• endodeoxyribonuclease complex
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Zinc finger, RING-type
• Zinc finger, RING/FYVE/PHD-type
• Zinc finger, RING-type, conserved site
• Zinc finger, C3HC4 RING-type
• Zinc finger C2H2 superfamily
• Zinc finger, C3HC4 type (RING finger)
• V(D)J recombination-activating protein 1, Zinc finger
• RAG nonamer-binding domain
• V(D)J recombination-activating protein 1
• RAG1 importin-binding
• V(D)J recombination-activating protein 1, DNA-binding domain
• V(D)J recombination-activating protein 1, pre-RNase H domain
• V(D)J recombination-activating protein 1, RNase H domain
• V(D)J recombination-activating protein 1, ZnC2 domain
• V(D)J recombination-activating protein 1, ZnH2 domain
• V(D)J recombination-activating protein 1, C-terminal domain
• V(D)J recombination-activating protein 1, RING finger, HC subclass
• Recombination-activating protein 1 zinc-finger domain
• RAG1 importin binding
• Recombination-activation protein 1 (RAG1) nonamer-binding domain
• Recombination-activation protein 1 (RAG1) DNA-binding domain
• Recombination-activation protein 1 (RAG1) pre-RNase H domain
• Recombination-activation protein 1 (RAG1) RNase H domain
• Recombination-activation protein 1 (RAG1) ZnC2 domain
• Recombination-activation protein 1 (RAG1) ZnH2 domain
• Recombination-activation protein 1 (RAG1) C-terminal domain

KeywordsUniProt

• Chromatin regulator
• DNA recombination
• DNA-binding
• Endonuclease
• Hydrolase
• Isopeptide bond
• Metal-binding
• Multifunctional enzyme
• Nuclease
• Nucleus
• SCID
• Transferase
• Ubl conjugation
• Ubl conjugation pathway
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of RAG1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• DCAF1
• KPNA1