RAG2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: RAG2_HUMAN
• UniProt AC: P55895
• Protein Name: V(D)J recombination-activating protein 2
• Gene Name: RAG2
• Organism: Homo sapiens (Human).
• Sequence Length: 527
• Subcellular Localization: Nucleus.
• Protein Description: 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)..
• Protein Sequence: MSLQMVTVSNNIALIQPGFSLMNFDGQVFFFGQKGWPKRSCPTGVFHLDVKHNHVKLKPTIFSKDSCYLPPLRYPATCTFKGSLESEKHQYIIHGGKTPNNEVSDKIYVMSIVCKNNKKVTFRCTEKDLVGDVPEARYGHSINVVYSRGKSMGVLFGGRSYMPSTHRTTEKWNSVADCLPCVFLVDFEFGCATSYILPELQDGLSFHVSIAKNDTIYILGGHSLANNIRPANLYRIRVDLPLGSPAVNCTVLPGGISVSSAILTQTNNDEFVIVGGYQLENQKRMICNIISLEDNKIEIREMETPDWTPDIKHSKIWFGSNMGNGTVFLGIPGDNKQVVSEGFYFYMLKCAEDDTNEEQTTFTNSQTSTEDPGDSTPFEDSEEFCFSAEANSFDGDDEFDTYNEDDEEDESETGYWITCCPTCDVDINTWVPFYSTELNKPAMIYCSHGDGHWVHAQCMDLAERTLIHLSAGSNKYYCNEHVEIARALHTPQRVLPLKKPPMKSLRKKGSGKILTPAKKSFLRRLFD

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Phosphorylation	------MSLQMVTVS ------CCCEEEEEE	27.58	24043423
7	Phosphorylation	-MSLQMVTVSNNIAL -CCCEEEEEECCEEE	16.93	24043423
9	Phosphorylation	SLQMVTVSNNIALIQ CCEEEEEECCEEEEC	18.13	24043423
20	Phosphorylation	ALIQPGFSLMNFDGQ EEECCCEEEEECCCE	32.40	24043423
63	Phosphorylation	KLKPTIFSKDSCYLP EECCEEECCCCCCCC	31.53	24719451
88	Ubiquitination	KGSLESEKHQYIIHG ECCCCCCCCEEEEEC	45.33	29967540
121	Phosphorylation	CKNNKKVTFRCTEKD ECCCCEEEEEECCCH	17.78	-
138	Phosphorylation	GDVPEARYGHSINVV CCCCHHHCCEEEEEE	26.66	22817900
146	Phosphorylation	GHSINVVYSRGKSMG CEEEEEEEECCCEEE	6.59	22817900
291	Phosphorylation	RMICNIISLEDNKIE EEEEEEEECCCCCEE	23.16	25159151
346	Phosphorylation	VSEGFYFYMLKCAED EECEEEEEEEEECCC	7.08	22817900
365	Phosphorylation	EQTTFTNSQTSTEDP CCEEEECCCCCCCCC	31.60	22817900
490	Phosphorylation	EIARALHTPQRVLPL HHHHHHCCCCCCCCC	23.20	22817900
520	Phosphorylation	ILTPAKKSFLRRLFD CCCHHHHHHHHHHCC	28.89	24719451

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
365	S	Phosphorylation	Kinase	PRKDC	P78527	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	SKP2	Q13309	PMID:15949444

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of RAG2_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of RAG2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
DCAF1_HUMAN	VPRBP	physical	22157821
DDB1_HUMAN	DDB1	physical	22157821
RAG1_HUMAN	RAG1	physical	9630231
RAG1_HUMAN	RAG1	physical	8777717
RAG1_HUMAN	RAG1	physical	14670978
IPO5_HUMAN	IPO5	physical	12861017
RAG1_HUMAN	RAG1	physical	25745109

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• 233650: Combined cellular and humoral immune defects with granulomas (CHIDG)
• 601457: Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-negative/NK-cell-positive (T(-)B(-)NK(+) SCID)
• 603554: Omenn syndrome (OS)
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.