dbPTM

MCL1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MCL1_HUMAN
UniProt AC	Q07820
Protein Name	Induced myeloid leukemia cell differentiation protein Mcl-1
Gene Name	MCL1
Organism	Homo sapiens (Human).
Sequence Length	350
Subcellular Localization	Membrane Single-pass membrane protein . Cytoplasm. Mitochondrion. Nucleus, nucleoplasm. Cytoplasmic, associated with mitochondria.
Protein Description	Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis..
Protein Sequence	MFGLKRNAVIGLNLYCGGAGLGAGSGGATRPGGRLLATEKEASARREIGGGEAGAVIGGSAGASPPSTLTPDSRRVARPPPIGAEVPDVTATPARLLFFAPTRRAAPLEEMEAPAADAIMSPEEELDGYEPEPLGKRPAVLPLLELVGESGNNTSTDGSLPSTPPPAEEEEDELYRQSLEIISRYLREQATGAKDTKPMGRSGATSRKALETLRRVGDGVQRNHETAFQGMLRKLDIKNEDDVKSLSRVMIHVFSDGVTNWGRIVTLISFGAFVAKHLKTINQESCIEPLAESITDVLVRTKRDWLVKQRGWDGFVEFFHVEDLEGGIRNVLLAFAGVAGVGAGLAYLIR

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
5	Ubiquitination	---MFGLKRNAVIGL ---CCCCCCCCEEEE	43.94	15989957
5	Methylation	---MFGLKRNAVIGL ---CCCCCCCCEEEE	43.94	115972869
40 (in isoform 2)	Ubiquitination	-	54.98	21906983
40 (in isoform 1)	Ubiquitination	-	54.98	21906983
40	Ubiquitination	GRLLATEKEASARRE CEEEEEHHHHHHHHH	54.98	15989957
60	Phosphorylation	AGAVIGGSAGASPPS CCCEEECCCCCCCCC	20.51	29255136
64	Phosphorylation	IGGSAGASPPSTLTP EECCCCCCCCCCCCC	36.10	29255136
67	Phosphorylation	SAGASPPSTLTPDSR CCCCCCCCCCCCCCC	39.16	29255136
68	Phosphorylation	AGASPPSTLTPDSRR CCCCCCCCCCCCCCC	40.19	29255136
70	Phosphorylation	ASPPSTLTPDSRRVA CCCCCCCCCCCCCCC	25.74	29255136
73	Phosphorylation	PSTLTPDSRRVARPP CCCCCCCCCCCCCCC	24.16	29255136
90	Phosphorylation	GAEVPDVTATPARLL CCCCCCCCCCCCCEE	31.99	29255136
92	Phosphorylation	EVPDVTATPARLLFF CCCCCCCCCCCEEEE	14.23	29255136
121	Phosphorylation	PAADAIMSPEEELDG CHHCCCCCCHHHHCC	24.05	28796482
129	Phosphorylation	PEEELDGYEPEPLGK CHHHHCCCCCCCCCC	28.16	28796482
136	Ubiquitination	YEPEPLGKRPAVLPL CCCCCCCCCCCHHHH	63.99	15989957
136 (in isoform 2)	Ubiquitination	-	63.99	-
150	Phosphorylation	LLELVGESGNNTSTD HHHHHCCCCCCCCCC	40.67	22817900
154	Phosphorylation	VGESGNNTSTDGSLP HCCCCCCCCCCCCCC	36.68	22817900
155	Phosphorylation	GESGNNTSTDGSLPS CCCCCCCCCCCCCCC	26.99	23909892
156	Phosphorylation	ESGNNTSTDGSLPST CCCCCCCCCCCCCCC	42.20	23909892
159	Phosphorylation	NNTSTDGSLPSTPPP CCCCCCCCCCCCCCC	39.66	21368834
162	Phosphorylation	STDGSLPSTPPPAEE CCCCCCCCCCCCCHH	59.86	25159151
163	Phosphorylation	TDGSLPSTPPPAEEE CCCCCCCCCCCCHHH	37.56	10766760
175	Phosphorylation	EEEEDELYRQSLEII HHHHHHHHHHHHHHH	12.45	27542207
194 (in isoform 2)	Ubiquitination	-	68.24	-
194	Ubiquitination	REQATGAKDTKPMGR HHHHCCCCCCCCCCC	68.24	15989957
197	Ubiquitination	ATGAKDTKPMGRSGA HCCCCCCCCCCCCCH	43.04	15989957
197 (in isoform 2)	Ubiquitination	-	43.04	-
202	Phosphorylation	DTKPMGRSGATSRKA CCCCCCCCCHHHHHH	27.35	28111955
205	Phosphorylation	PMGRSGATSRKALET CCCCCCHHHHHHHHH	32.37	28111955
206	Phosphorylation	MGRSGATSRKALETL CCCCCHHHHHHHHHH	31.11	28111955
208	Ubiquitination	RSGATSRKALETLRR CCCHHHHHHHHHHHH	58.03	PubMed
234	Ubiquitination	AFQGMLRKLDIKNED HHHHHHHHCCCCCHH	46.69	15989957PubMed
238	Ubiquitination	MLRKLDIKNEDDVKS HHHHCCCCCHHHHHH	54.68	-
244 (in isoform 1)	Ubiquitination	-	53.31	21906983
244	Ubiquitination	IKNEDDVKSLSRVMI CCCHHHHHHHHHHEE	53.31	2190698
245	Phosphorylation	KNEDDVKSLSRVMIH CCHHHHHHHHHHEEH	31.27	29214152
247	Phosphorylation	EDDVKSLSRVMIHVF HHHHHHHHHHEEHHH	29.89	29214152
255	Phosphorylation	RVMIHVFSDGVTNWG HHEEHHHCCCCCCHH	32.16	27251275
258 (in isoform 2)	Phosphorylation	-	4.49	29083192
260 (in isoform 2)	Phosphorylation	-	36.48	29083192
265 (in isoform 2)	Phosphorylation	-	3.25	29083192
276	Ubiquitination	SFGAFVAKHLKTINQ HHHHHHHHHHHHCCH	44.14	-
279	Ubiquitination	AFVAKHLKTINQESC HHHHHHHHHCCHHHC	47.26	-
301	Phosphorylation	ITDVLVRTKRDWLVK HHHHHHHHHHHHHHH	23.97	-
302	Ubiquitination	TDVLVRTKRDWLVKQ HHHHHHHHHHHHHHC	37.48	-
308	Ubiquitination	TKRDWLVKQRGWDGF HHHHHHHHCCCCCCE	31.91	-
347	Phosphorylation	GVGAGLAYLIR---- CHHCHHHHHHC----	14.01	20068231

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
64	S	Phosphorylation	Kinase	CDK1	P06493	PSP
64	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
64	S	Phosphorylation	Kinase	CDK2	P24941	PSP
70	T	Phosphorylation	Kinase	CDK2	P24941	PSP
92	T	Phosphorylation	Kinase	CDK1	P06493	PSP
92	T	Phosphorylation	Kinase	CDK2	P24941	PSP
92	T	Phosphorylation	Kinase	CDK5	Q00535	PSP
92	T	Phosphorylation	Kinase	MAPK3	P27361	GPS
121	S	Phosphorylation	Kinase	CDK2	P24941	PSP
121	S	Phosphorylation	Kinase	P38-SUBFAMILY	-	GPS
121	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
121	S	Phosphorylation	Kinase	JNK-SUBFAMILY	-	GPS
121	S	Phosphorylation	Kinase	MAPK8	P45983	GPS
159	S	Phosphorylation	Kinase	GSK3-ALPHA	P49840	Uniprot
159	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
163	T	Phosphorylation	Kinase	P38-SUBFAMILY	-	GPS
163	T	Phosphorylation	Kinase	JNK-SUBFAMILY	-	GPS
163	T	Phosphorylation	Kinase	MAPK	-	Uniprot
163	T	Phosphorylation	Kinase	MAPK8	P45983	GPS
163	T	Phosphorylation	Kinase	MAPK3	P27361	GPS
163	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
163	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
163	T	Phosphorylation	Kinase	CDK2	P24941	PSP
301	T	Phosphorylation	Kinase	AURB	Q96GD4	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	HUWE1	Q7Z6Z7	PMID:16213503
-	K	Ubiquitination	E3 ubiquitin ligase	CDC20	Q12834	PMID:20526282
-	K	Ubiquitination	E3 ubiquitin ligase	FBXW7	Q969H0	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	BTRC	Q9Y297	PMID:24658274
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM17	Q9Y577	PMID:22976837
-	K	Ubiquitination	E3 ubiquitin ligase	FBXO4	Q9UKT5	PMID:28776569

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
159	S	Phosphorylation	16543145
Phosphorylated on Ser-159, by GSK3, in response to IL3/interleukin-3 withdrawal.
159	S	Phosphorylation	16543145
Phosphorylation at Ser-159 induces ubiquitination and proteasomal degradation, abrogating the anti-apoptotic activity.
159	S	Phosphorylation	16543145
Ubiquitination is induced by phosphorylation at Ser-159.
159	S	ubiquitylation	16543145
Phosphorylation at Ser-159 induces ubiquitination and proteasomal degradation, abrogating the anti-apoptotic activity.
159	S	ubiquitylation	16543145
Ubiquitination is induced by phosphorylation at Ser-159.
163	T	Phosphorylation	12223490
Rapidly degraded in the absence of phosphorylation on Thr-163 in the PEST region.

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 MCL1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
BAD_HUMAN	BAD	physical	11483855
BOK_HUMAN	BOK	physical	9356461
BMF_HUMAN	BMF	physical	15694340
BAD_HUMAN	BAD	physical	15694340
BIK_HUMAN	BIK	physical	15694340
HRK_HUMAN	HRK	physical	15694340
BID_HUMAN	BID	physical	15694340
BAK_HUMAN	BAK1	physical	15077116
BAK_HUMAN	BAK1	physical	15901672
BAK_HUMAN	BAK1	physical	15637055
BID_HUMAN	BID	physical	15637055
VDAC1_HUMAN	VDAC1	physical	15637055
MCL1_HUMAN	MCL1	physical	10837489
B2CL1_HUMAN	BCL2L1	physical	10837489
TNKS1_HUMAN	TNKS	physical	12475993
PIN1_HUMAN	PIN1	physical	17670986
B2L11_HUMAN	BCL2L11	physical	20074640
B2L11_HUMAN	BCL2L11	physical	21613222
BAK_HUMAN	BAK1	physical	21613222
BBC3B_HUMAN	BBC3	physical	21613222
BBC3_HUMAN	BBC3	physical	21613222
BID_HUMAN	BID	physical	21613222
APR_HUMAN	PMAIP1	physical	21613222
HUWE1_HUMAN	HUWE1	physical	21613222
BIK_HUMAN	BIK	physical	21613222
HUWE1_HUMAN	HUWE1	physical	21907705
USP9X_HUMAN	USP9X	physical	21907705
USP9X_HUMAN	USP9X	physical	20023629
HUWE1_HUMAN	HUWE1	physical	20023629
B2L11_HUMAN	BCL2L11	physical	19622586
HUWE1_HUMAN	HUWE1	physical	21730980
APR_HUMAN	PMAIP1	physical	21139584
HSP74_HUMAN	HSPA4	physical	21298030
HUWE1_HUMAN	HUWE1	physical	21298030
HUWE1_HUMAN	HUWE1	physical	22552282
B2L11_HUMAN	BCL2L11	physical	19148187
APR_HUMAN	PMAIP1	physical	19148187
BAK_HUMAN	BAK1	physical	19148187
BAX_HUMAN	BAX	physical	19148187
HUWE1_HUMAN	HUWE1	physical	19148187
HSP74_HUMAN	HSPA4	physical	19148187
HSP7C_HUMAN	HSPA8	physical	19148187
APR_HUMAN	PMAIP1	physical	22361683
B2L11_HUMAN	BCL2L11	physical	15989957
HUWE1_HUMAN	HUWE1	physical	15989957
USP9X_HUMAN	USP9X	physical	23171055
B2L11_HUMAN	BCL2L11	physical	21507240
HUWE1_HUMAN	HUWE1	physical	21507240
MCL1_HUMAN	MCL1	physical	19683529
CAV1_HUMAN	CAV1	physical	22277751
BAG3_HUMAN	BAG3	physical	23341456
APR_HUMAN	PMAIP1	physical	23341456
BAG4_HUMAN	BAG4	physical	23341456
BECN1_HUMAN	BECN1	physical	22219388
APR_HUMAN	PMAIP1	physical	22219388
BAX_HUMAN	BAX	physical	21566062
P53_HUMAN	TP53	physical	24491548
PRKN_HUMAN	PARK2	physical	24999239
PINK1_HUMAN	PINK1	physical	24999239
B2L11_HUMAN	BCL2L11	physical	15721256
BMF_HUMAN	BMF	physical	15721256
BBC3B_HUMAN	BBC3	physical	15721256
BBC3_HUMAN	BBC3	physical	15721256
APR_HUMAN	PMAIP1	physical	15721256
BID_HUMAN	BID	physical	19074266
HUWE1_HUMAN	HUWE1	physical	25147182
TRAF6_HUMAN	TRAF6	physical	25340740
BID_HUMAN	BID	physical	16697956
B2L11_HUMAN	BCL2L11	physical	16697956
BIK_HUMAN	BIK	physical	16697956
APR_HUMAN	PMAIP1	physical	16697956
BBC3B_HUMAN	BBC3	physical	16697956
BBC3_HUMAN	BBC3	physical	16697956
BMF_HUMAN	BMF	physical	16697956
BECN1_HUMAN	BECN1	physical	21139567
AAKG1_HUMAN	PRKAG1	physical	26186194
STAR9_HUMAN	STARD9	physical	26186194
CPT2_HUMAN	CPT2	physical	26186194
AAKB1_HUMAN	PRKAB1	physical	26186194
AAKB2_HUMAN	PRKAB2	physical	26186194
APRV1_HUMAN	ASPRV1	physical	26186194
FILA_HUMAN	FLG	physical	26186194
AAPK1_HUMAN	PRKAA1	physical	26186194
BAK_HUMAN	BAK1	physical	26186194
TRI11_HUMAN	TRIM11	physical	26186194
ECM1_HUMAN	ECM1	physical	26186194
BAX_HUMAN	BAX	physical	26186194
SPB7_HUMAN	SERPINB7	physical	26186194
BBC3B_HUMAN	BBC3	physical	26186194
BBC3_HUMAN	BBC3	physical	26186194
BAK_HUMAN	BAK1	physical	26045051
APR_HUMAN	PMAIP1	physical	26045051
B2L11_HUMAN	BCL2L11	physical	26045051
B2L11_HUMAN	BCL2L11	physical	20836993
BAK_HUMAN	BAK1	physical	20836993
UBXN6_HUMAN	UBXN6	physical	27913212
BAK_HUMAN	BAK1	physical	27818144
FBXW7_HUMAN	FBXW7	physical	28202514
BBC3B_HUMAN	BBC3	physical	28202514
BBC3_HUMAN	BBC3	physical	28202514
BAK_HUMAN	BAK1	physical	28514442
BBC3B_HUMAN	BBC3	physical	28514442
BBC3_HUMAN	BBC3	physical	28514442
BAX_HUMAN	BAX	physical	28514442
TRI11_HUMAN	TRIM11	physical	28514442
AAPK1_HUMAN	PRKAA1	physical	28514442
SPB7_HUMAN	SERPINB7	physical	28514442
STAR9_HUMAN	STARD9	physical	28514442
AAKB1_HUMAN	PRKAB1	physical	28514442
AAKB2_HUMAN	PRKAB2	physical	28514442
ECM1_HUMAN	ECM1	physical	28514442
ARGI1_HUMAN	ARG1	physical	28514442
APRV1_HUMAN	ASPRV1	physical	28514442
CPT2_HUMAN	CPT2	physical	28514442
FBXW7_HUMAN	FBXW7	physical	28522751
CUL1_HUMAN	CUL1	physical	28522751
SKP1_HUMAN	SKP1	physical	28522751
FBXW7_HUMAN	FBXW7	physical	28619760

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
D09935	Navitoclax (USAN/INN)
D09936	Navitoclax dihydrochloride (USAN)
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of MCL1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK inresponse to oxidative stress."; Inoshita S., Takeda K., Hatai T., Terada Y., Sano M., Hata J.,Umezawa A., Ichijo H.; J. Biol. Chem. 277:43730-43734(2002). Cited for: PHOSPHORYLATION AT SER-121 AND THR-163.	12223490 [Abstract]
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient phosphoproteomic analysis."; Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,Yates J.R. III; J. Proteome Res. 7:1346-1351(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-163, AND MASSSPECTROMETRY.	18220336 [Abstract]
"MCL1 is phosphorylated in the PEST region and stabilized upon ERKactivation in viable cells, and at additional sites with cytotoxicokadaic acid or taxol."; Domina A.M., Vrana J.A., Gregory M.A., Hann S.R., Craig R.W.; Oncogene 23:5301-5315(2004). Cited for: PHOSPHORYLATION AT THR-163, AND MUTAGENESIS OF SER-162 AND THR-163.	15241487 [Abstract]

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