dbPTM

BCL2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	BCL2_HUMAN
UniProt AC	P10415
Protein Name	Apoptosis regulator Bcl-2
Gene Name	BCL2
Organism	Homo sapiens (Human).
Sequence Length	239
Subcellular Localization	Mitochondrion outer membrane Single-pass membrane protein . Nucleus membrane Single-pass membrane protein . Endoplasmic reticulum membrane Single-pass membrane protein .
Protein Description	Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release. [PubMed: 17418785]
Protein Sequence	MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPAASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEYLNRHLHTWIQDNGGWDAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
9	Phosphorylation	AHAGRTGYDNREIVM CCCCCCCCCHHHHHH	14.94	-
22	Ubiquitination	VMKYIHYKLSQRGYE HHHHHHHHHHHCCCC	27.74	-
24	Phosphorylation	KYIHYKLSQRGYEWD HHHHHHHHHCCCCCC	17.43	9738012
56	Phosphorylation	FSSQPGHTPHPAASR CCCCCCCCCCCCHHC	29.25	12039864
69	Phosphorylation	SRDPVARTSPLQTPA HCCCCCCCCCCCCCC	25.59	15703383
70	Phosphorylation	RDPVARTSPLQTPAA CCCCCCCCCCCCCCC	20.33	15026553
74	Phosphorylation	ARTSPLQTPAAPGAA CCCCCCCCCCCCCCC	23.68	9312139
87	Dephosphorylation	AAAGPALSPVPPVVH CCCCCCCCCCCCEEE	26.42	10669763
87	Phosphorylation	AAAGPALSPVPPVVH CCCCCCCCCCCCEEE	26.42	26055452
158	S-nitrosocysteine	FEFGGVMCVESVNRE EEECCEEEHHHHCHH	2.60	-
158	S-nitrosylation	FEFGGVMCVESVNRE EEECCEEEHHHHCHH	2.60	22178444
216	Phosphorylation	LFDFSWLSLKTLLSL CCCCCHHHHHHHHHH	22.89	28961369
229	S-nitrosocysteine	SLALVGACITLGAYL HHHHHHHHHHHHHHH	1.69	-
229	S-nitrosylation	SLALVGACITLGAYL HHHHHHHHHHHHHHH	1.69	22178444
235	Phosphorylation	ACITLGAYLGHK--- HHHHHHHHHCCC---	16.06	18083107

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
56	T	Phosphorylation	Kinase	CDK1	P06493	PSP
56	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
56	T	Phosphorylation	Kinase	MAPK3	P27361	GPS
56	T	Phosphorylation	Kinase	MAPK14	Q16539	GPS
56	T	Phosphorylation	Kinase	MAPK10	Q61831	GPS
56	T	Phosphorylation	Kinase	MAPK9	P45984	GPS
69	T	Phosphorylation	Kinase	MAPK_GROUP	-	PhosphoELM
69	T	Phosphorylation	Kinase	JNK1	P45983	PSP
69	T	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
70	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
70	S	Phosphorylation	Kinase	MAPK_GROUP	-	PhosphoELM
70	S	Phosphorylation	Kinase	PKC	-	Uniprot
70	S	Phosphorylation	Kinase	PKC-FAMILY	-	GPS
70	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
70	S	Phosphorylation	Kinase	MAPK10	Q61831	GPS
70	S	Phosphorylation	Kinase	MAPK9	P45984	GPS
70	S	Phosphorylation	Kinase	MK08	P45983	PhosphoELM
70	S	Phosphorylation	Kinase	PKCD	Q05655	PSP
74	T	Phosphorylation	Kinase	MAPK10	Q61831	GPS
74	T	Phosphorylation	Kinase	MAPK9	P45984	GPS
74	T	Phosphorylation	Kinase	MAPK3	P27361	GPS
74	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
87	S	Phosphorylation	Kinase	MAPK10	Q61831	GPS
87	S	Phosphorylation	Kinase	MAPK9	P45984	GPS
87	S	Phosphorylation	Kinase	MK08	P45983	PhosphoELM
87	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
87	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
87	S	Phosphorylation	Kinase	MAPK3	P27361	GPS
87	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
87	S	Phosphorylation	Kinase	MAPK_GROUP	-	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	PPARA	Q07869	PMID:26556865
-	K	Ubiquitination	E3 ubiquitin ligase	FBXO10	Q9UK96	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	PRKN	O60260	PMID:20889974

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
69	T	Phosphorylation	18570871
Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophagy.
70	S	Phosphorylation	18570871
Growth factor-stimulated phosphorylation on Ser-70 by PKC is required for the anti-apoptosis activity and occurs during the G2/M phase of the cell cycle.
70	S	Phosphorylation	18570871
Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophagy.
70	S	Phosphorylation	18570871
Phosphorylation/dephosphorylation on Ser-70 regulates anti-apoptotic activity.
87	S	Phosphorylation	18570871
Phosphorylated by MAPK8/JNK1 at Thr-69, Ser-70 and Ser-87, wich stimulates starvation-induced autophagy.

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of BCL2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
BECN1_HUMAN	BECN1	physical	9765397
BIK_HUMAN	BIK	physical	15694340
HRK_HUMAN	HRK	physical	15694340
BID_HUMAN	BID	physical	15694340
APR_HUMAN	PMAIP1	physical	15694340
ITPR1_HUMAN	ITPR1	physical	15613488
BAX_HUMAN	BAX	physical	15231068
SPB8_HUMAN	SERPINB8	physical	15231068
MYC_HUMAN	MYC	physical	15210690
SODC_HUMAN	SOD1	physical	15233914
BAX_HUMAN	BAX	physical	14980220
NR4A1_HUMAN	NR4A1	physical	14980220
BAK_HUMAN	BAK1	physical	14980220
B2CL1_HUMAN	BCL2L1	physical	14980220
RRAS_HUMAN	RRAS	physical	8232588
RAF1_HUMAN	RAF1	physical	8929532
RTN4_HUMAN	RTN4	physical	11126360
BECN1_MOUSE	Becn1	physical	9765397
RAD9A_HUMAN	RAD9A	physical	10620799
IRS1_HUMAN	IRS1	physical	10679027
IRS2_HUMAN	IRS2	physical	10679027
PSN1_HUMAN	PSEN1	physical	10521466
BMF_HUMAN	BMF	physical	11546872
CDK1_HUMAN	CDK1	physical	11774038
CDK1_HUMAN	CDK1	physical	11326318
PIN1_HUMAN	PIN1	physical	11326318
2A5A_HUMAN	PPP2R5A	physical	11929874
BBC3B_HUMAN	BBC3	physical	11463392
BBC3_HUMAN	BBC3	physical	11463392
PP2AA_HUMAN	PPP2CA	physical	9852076
CASP8_HUMAN	CASP8	physical	11406564
FKBP8_HUMAN	FKBP8	physical	12510191
PP2BA_HUMAN	PPP3CA	physical	9109491
DYL1_HUMAN	DYNLL1	physical	10198631
B2L11_MOUSE	Bcl2l11	physical	10198631
BAK_HUMAN	BAK1	physical	11728179
SMN_HUMAN	SMN1	physical	9389483
BNIP2_HUMAN	BNIP2	physical	7954800
BNIP3_HUMAN	BNIP3	physical	7954800
B2L11_HUMAN	BCL2L11	physical	9430630
BNI3L_HUMAN	BNIP3L	physical	10467396
BNIP3_HUMAN	BNIP3	physical	10625696
RAD9A_HUMAN	RAD9A	physical	18794804
B2L11_HUMAN	BCL2L11	physical	19805519
BECN1_HUMAN	BECN1	physical	20889974
BECN1_HUMAN	BECN1	physical	21543763
HS90A_HUMAN	HSP90AA1	physical	21543763
FKBP8_HUMAN	FKBP8	physical	17379601
ITLN1_HUMAN	ITLN1	genetic	22647378
BECN1_HUMAN	BECN1	physical	20010695
MEX3D_HUMAN	MEX3D	physical	14769789
HNRPD_HUMAN	HNRNPD	physical	14769789
P53_HUMAN	TP53	physical	21597459
BIK_HUMAN	BIK	physical	9488477
BRCA1_HUMAN	BRCA1	physical	21444675
NR4A1_HUMAN	NR4A1	physical	16434970
AMRA1_HUMAN	AMBRA1	physical	21358617
BECN1_HUMAN	BECN1	physical	21358617
CRYAB_HUMAN	CRYAB	physical	20841355
BAX_HUMAN	BAX	physical	22262057
IKKB_HUMAN	IKBKB	physical	22262057
IKKA_HUMAN	CHUK	physical	22262057
HIF1A_HUMAN	HIF1A	physical	20668552
FKBP8_HUMAN	FKBP8	physical	15990872
BAD_HUMAN	BAD	physical	15990872
FKBP8_HUMAN	FKBP8	physical	17942410
RAF1_HUMAN	RAF1	physical	15849194
MDM4_HUMAN	MDM4	physical	19521340
P53_HUMAN	TP53	physical	19521340
PP2BC_HUMAN	PPP3CC	physical	15757646
SQSTM_HUMAN	SQSTM1	physical	23564079
BECN1_HUMAN	BECN1	physical	23564079
RAF1_HUMAN	RAF1	physical	12488548
BECN1_HUMAN	BECN1	physical	21971985
BECN1_HUMAN	BECN1	physical	22622204
BAX_HUMAN	BAX	physical	10716992
BNIP3_HUMAN	BNIP3	physical	23504944
BECN1_HUMAN	BECN1	physical	23504944
PPID_HUMAN	PPID	physical	19228691
RASK_HUMAN	KRAS	physical	19433448
ASPP2_HUMAN	TP53BP2	physical	18719108
NR4A1_HUMAN	NR4A1	physical	18835031
BCL2_HUMAN	BCL2	physical	18835031
B2CL1_HUMAN	BCL2L1	physical	18835031
BID_HUMAN	BID	physical	19074266
BCL2_HUMAN	BCL2	physical	9111042
BAD_HUMAN	BAD	physical	9305851
BECN1_HUMAN	BECN1	physical	16179260
ITPR1_HUMAN	ITPR1	physical	19706527
PP2BA_HUMAN	PPP3CA	physical	19706527
VDAC1_HUMAN	VDAC1	physical	19706527
BAX_MOUSE	Bax	physical	9742125
GIMA5_HUMAN	GIMAP5	physical	16509771
BID_HUMAN	BID	physical	16697956
B2L11_HUMAN	BCL2L11	physical	16697956
BAD_HUMAN	BAD	physical	16697956
BIK_HUMAN	BIK	physical	16697956
BBC3B_HUMAN	BBC3	physical	16697956
BBC3_HUMAN	BBC3	physical	16697956
BMF_HUMAN	BMF	physical	16697956
BECN1_HUMAN	BECN1	physical	20622903
B2L11_HUMAN	BCL2L11	physical	17074758
BAX_HUMAN	BAX	physical	17097560
BNI3L_HUMAN	BNIP3L	physical	9973195
MK01_HUMAN	MAPK1	physical	15225643
PP2AA_HUMAN	PPP2CA	physical	15225643
PPARA_HUMAN	PPARA	physical	26556865
METK2_HUMAN	MAT2A	physical	26416353
UBC9_HUMAN	UBE2I	physical	26416353
BECN1_HUMAN	BECN1	physical	25984893
B2L11_HUMAN	BCL2L11	physical	20836993
BAK_HUMAN	BAK1	physical	20836993
CDK4_HUMAN	CDK4	genetic	28319113
RTN3_HUMAN	RTN3	physical	17191123
RTN4_HUMAN	RTN4	physical	17191123
BECN1_HUMAN	BECN1	physical	24599950

Drug and Disease Associations

Kegg Disease
H00005	Chronic lymphocytic leukemia (CLL)
H00013	Small cell lung cancer
H00018	Gastric cancer
H00028	Choriocarcinoma
H00030	Cervical cancer
H00041	Kaposi's sarcoma
H00054	Nasopharyngeal cancer
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D05216	Oblimersen sodium (USAN); Genasense (TN)
D08290	Oblimersen (INN)
D08954	Obatoclax mesylate (USAN)
DrugBank
DB01248	Docetaxel
DB01050	Ibuprofen
DB01229	Paclitaxel
DB01367	Rasagiline

Regulatory Network of BCL2_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"JNK1-mediated phosphorylation of Bcl-2 regulates starvation-inducedautophagy."; Wei Y., Pattingre S., Sinha S., Bassik M., Levine B.; Mol. Cell 30:678-688(2008). Cited for: PHOSPHORYLATION AT THR-69; SER-70 AND SER-87 BY MAPK8/JNK1, ANDFUNCTION.	18570871 [Abstract]

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