RAG1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: RAG1_HUMAN
• UniProt AC: P15918
• Protein Name: V(D)J recombination-activating protein 1
• Gene Name: RAG1
• Organism: Homo sapiens (Human).
• Sequence Length: 1043
• Subcellular Localization: Nucleus .
• Protein Description: 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 an 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)..
• Protein Sequence: MAASFPPTLGLSSAPDEIQHPHIKFSEWKFKLFRVRSFEKTPEEAQKEKKDSFEGKPSLEQSPAVLDKADGQKPVPTQPLLKAHPKFSKKFHDNEKARGKAIHQANLRHLCRICGNSFRADEHNRRYPVHGPVDGKTLGLLRKKEKRATSWPDLIAKVFRIDVKADVDSIHPTEFCHNCWSIMHRKFSSAPCEVYFPRNVTMEWHPHTPSCDICNTARRGLKRKSLQPNLQLSKKLKTVLDQARQARQHKRRAQARISSKDVMKKIANCSKIHLSTKLLAVDFPEHFVKSISCQICEHILADPVETNCKHVFCRVCILRCLKVMGSYCPSCRYPCFPTDLESPVKSFLSVLNSLMVKCPAKECNEEVSLEKYNHHISSHKESKEIFVHINKGGRPRQHLLSLTRRAQKHRLRELKLQVKAFADKEEGGDVKSVCMTLFLLALRARNEHRQADELEAIMQGKGSGLQPAVCLAIRVNTFLSCSQYHKMYRTVKAITGRQIFQPLHALRNAEKVLLPGYHHFEWQPPLKNVSSSTDVGIIDGLSGLSSSVDDYPVDTIAKRFRYDSALVSALMDMEEDILEGMRSQDLDDYLNGPFTVVVKESCDGMGDVSEKHGSGPVVPEKAVRFSFTIMKITIAHSSQNVKVFEEAKPNSELCCKPLCLMLADESDHETLTAILSPLIAEREAMKSSELMLELGGILRTFKFIFRGTGYDEKLVREVEGLEASGSVYICTLCDATRLEASQNLVFHSITRSHAENLERYEVWRSNPYHESVEELRDRVKGVSAKPFIETVPSIDALHCDIGNAAEFYKIFQLEIGEVYKNPNASKEERKRWQATLDKHLRKKMNLKPIMRMNGNFARKLMTKETVDAVCELIPSEERHEALRELMDLYLKMKPVWRSSCPAKECPESLCQYSFNSQRFAELLSTKFKYRYEGKITNYFHKTLAHVPEIIERDGSIGAWASEGNESGNKLFRRFRKMNARQSKCYEMEDVLKHHWLYTSKYLQKFMNAHNALKTSGFTMNPQASLGDPLGIEDSLESQDSMEF

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
37	Phosphorylation	FKLFRVRSFEKTPEE EEEEEEECCCCCHHH	34.59	23312004
41	Phosphorylation	RVRSFEKTPEEAQKE EEECCCCCHHHHHHH	28.83	23312004
52	Phosphorylation	AQKEKKDSFEGKPSL HHHHHHCCCCCCCCH	33.79	29116813
73	Ubiquitination	LDKADGQKPVPTQPL HHCCCCCCCCCCHHH	54.21	-
82	Ubiquitination	VPTQPLLKAHPKFSK CCCHHHHHHCCCHHH	52.94	21853274
127	Phosphorylation	ADEHNRRYPVHGPVD CCCCCCCCCCCCCCC	13.33	21214269
137	Phosphorylation	HGPVDGKTLGLLRKK CCCCCCCCHHHHHHH	31.42	21214269
169	Phosphorylation	DVKADVDSIHPTEFC EECCCCCCCCCCHHH	23.73	30177828
173	Phosphorylation	DVDSIHPTEFCHNCW CCCCCCCCHHHHHHH	27.77	30177828
181	Phosphorylation	EFCHNCWSIMHRKFS HHHHHHHHHHHHHCC	16.54	30177828
195	Phosphorylation	SSAPCEVYFPRNVTM CCCCEEEEECCCCCE	5.88	-
238	Phosphorylation	QLSKKLKTVLDQARQ HHHHHHHHHHHHHHH	36.42	-
322	Ubiquitination	VCILRCLKVMGSYCP HHHHHHHHHHHHCCC	33.53	-
401	Phosphorylation	RPRQHLLSLTRRAQK CCHHHHHHHHHHHHH	33.77	24719451
530	Phosphorylation	QPPLKNVSSSTDVGI CCCCCCCCCCCCCEE	28.15	-
532	Phosphorylation	PLKNVSSSTDVGIID CCCCCCCCCCCEEEC	22.56	-
702	Ubiquitination	GGILRTFKFIFRGTG HHHHHHHHHHHCCCC	36.62	-
702	Ubiquitination	GGILRTFKFIFRGTG HHHHHHHHHHHCCCC	36.62	-
741	Phosphorylation	DATRLEASQNLVFHS CCCCCHHHHHHHHHH	15.38	24719451
865	Phosphorylation	RKLMTKETVDAVCEL HHHCCHHHHHHHHHH	25.82	26657352
903	Ubiquitination	WRSSCPAKECPESLC CCCCCCHHHCCHHHH	45.02	-
924	Phosphorylation	QRFAELLSTKFKYRY HHHHHHHCCCEEEEE	42.02	24719451
983	Acetylation	KMNARQSKCYEMEDV HHCHHHCCCCCHHHH	32.28	70127

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
-	K	Ubiquitination	E3 ubiquitin ligase	RAG1	P15918	PMID:14671314

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of RAG1_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 RAG1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
IMA5_HUMAN	KPNA1	physical	8052633
RAG2_HUMAN	RAG2	physical	9036966
HMGB1_HUMAN	HMGB1	physical	10490593
HMGB2_HUMAN	HMGB2	physical	10490593
IMA1_HUMAN	KPNA2	physical	8016130
H31T_HUMAN	HIST3H3	physical	20122409
H2A2C_HUMAN	HIST2H2AC	physical	20122409
H2B2E_HUMAN	HIST2H2BE	physical	20122409
H31_HUMAN	HIST1H3A	physical	21256161
DCAF1_HUMAN	VPRBP	physical	22157821
DDB1_HUMAN	DDB1	physical	22157821
RBX1_HUMAN	RBX1	physical	22157821
CUL4A_HUMAN	CUL4A	physical	22157821
RAG2_HUMAN	RAG2	physical	9630231
RAG2_HUMAN	RAG2	physical	8777717
IMA5_HUMAN	KPNA1	physical	8777717
IMA1_HUMAN	KPNA2	physical	8777717
UB2D2_HUMAN	UBE2D2	physical	20122409
UBE2H_HUMAN	UBE2H	physical	21256161
MDC1_HUMAN	MDC1	physical	22942284
RUNX1_HUMAN	RUNX1	physical	25135298
UB2D2_HUMAN	UBE2D2	physical	12629039
UBE2C_HUMAN	UBE2C	physical	12629039
UBC_HUMAN	UBC	physical	12629039
RAG2_HUMAN	RAG2	physical	26124138
RAG1_HUMAN	RAG1	physical	26124138
UB2D1_HUMAN	UBE2D1	physical	26124138
UB2D2_HUMAN	UBE2D2	physical	26124138

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.