dbPTM

MLKL_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MLKL_HUMAN
UniProt AC	Q8NB16
Protein Name	Mixed lineage kinase domain-like protein
Gene Name	MLKL {ECO:0000312\|EMBL:AAH28141.1}
Organism	Homo sapiens (Human).
Sequence Length	471
Subcellular Localization	Cytoplasm . Cell membrane . Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction.
Protein Description	Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process. Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage. Does not have protein kinase activity..
Protein Sequence	MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQDQGKRSVPSEKLTTAMNRFKAALEEANGEIEKFSNRSNICRFLTASQDKILFKDVNRKLSDVWKELSLLLQVEQRMPVSPISQGASWAQEDQQDADEDRRAFQMLRRDNEKIEASLRRLEINMKEIKETLRQYLPPKCMQEIPQEQIKEIKKEQLSGSPWILLRENEVSTLYKGEYHRAPVAIKVFKKLQAGSIAIVRQTFNKEIKTMKKFESPNILRIFGICIDETVTPPQFSIVMEYCELGTLRELLDREKDLTLGKRMVLVLGAARGLYRLHHSEAPELHGKIRSSNFLVTQGYQVKLAGFELRKTQTSMSLGTTREKTDRVKSTAYLSPQELEDVFYQYDVKSEIYSFGIVLWEIATGDIPFQGCNSEKIRKLVAVKRQQEPLGEDCPSELREIIDECRAHDPSVRPSVDEILKKLSTFSK

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
16	Acetylation	TLGQVIHKRCEEMKY HHHHHHHHHHHHHHH	47.85	26051181
22	Ubiquitination	HKRCEEMKYCKKQCR HHHHHHHHHHHHHHH	51.26	24816145
40	Ubiquitination	HRVLGLIKPLEMLQD HHHHHHHHHHHHHHH	48.90	29967540
50	Ubiquitination	EMLQDQGKRSVPSEK HHHHHCCCCCCCHHH	35.55	33845483
52	Phosphorylation	LQDQGKRSVPSEKLT HHHCCCCCCCHHHHH	41.69	23403867
55	Phosphorylation	QGKRSVPSEKLTTAM CCCCCCCHHHHHHHH	45.25	23403867
57	Ubiquitination	KRSVPSEKLTTAMNR CCCCCHHHHHHHHHH	56.31	24816145
59	Phosphorylation	SVPSEKLTTAMNRFK CCCHHHHHHHHHHHH	24.47	23403867
60	Phosphorylation	VPSEKLTTAMNRFKA CCHHHHHHHHHHHHH	34.05	23403867
66	Acetylation	TTAMNRFKAALEEAN HHHHHHHHHHHHHHC	29.52	26051181
66	Ubiquitination	TTAMNRFKAALEEAN HHHHHHHHHHHHHHC	29.52	29967540
78	Ubiquitination	EANGEIEKFSNRSNI HHCCHHHHHCCCCCH	60.81	29967540
92	Phosphorylation	ICRFLTASQDKILFK HHHHHHCCCCCEEHH	33.41	25159151
95	Acetylation	FLTASQDKILFKDVN HHHCCCCCEEHHHHC	33.40	25953088
106	Phosphorylation	KDVNRKLSDVWKELS HHHCHHHHHHHHHHH	32.90	20873877
125	Phosphorylation	VEQRMPVSPISQGAS HHHHCCCCCCCCCCC	15.62	25159151
128	Phosphorylation	RMPVSPISQGASWAQ HCCCCCCCCCCCHHH	26.41	21815630
132	Phosphorylation	SPISQGASWAQEDQQ CCCCCCCCHHHHHHC	29.75	22468782
157	Ubiquitination	MLRRDNEKIEASLRR HHHHCHHHHHHHHHH	52.69	29967540
157	Acetylation	MLRRDNEKIEASLRR HHHHCHHHHHHHHHH	52.69	25953088
161	Phosphorylation	DNEKIEASLRRLEIN CHHHHHHHHHHHHCC	15.04	29514088
173	Ubiquitination	EINMKEIKETLRQYL HCCHHHHHHHHHHHC	45.82	29967540
183	Ubiquitination	LRQYLPPKCMQEIPQ HHHHCCHHHHCCCCH	40.16	29967540
198	Ubiquitination	EQIKEIKKEQLSGSP HHHHHHHHHHHCCCC	57.25	29967540
215	Phosphorylation	LLRENEVSTLYKGEY EEECCCCCCCCCCCC	13.40	30108239
216	Phosphorylation	LRENEVSTLYKGEYH EECCCCCCCCCCCCC	39.00	30108239
218	Phosphorylation	ENEVSTLYKGEYHRA CCCCCCCCCCCCCCC	19.62	30108239
219	Ubiquitination	NEVSTLYKGEYHRAP CCCCCCCCCCCCCCC	48.67	29967540
222	Phosphorylation	STLYKGEYHRAPVAI CCCCCCCCCCCCHHH	12.79	30108239
230	Ubiquitination	HRAPVAIKVFKKLQA CCCCHHHHHHHHCCC	31.70	29967540
246	Phosphorylation	SIAIVRQTFNKEIKT CEEEEEHHHCHHHHH	20.72	20393185
249	Ubiquitination	IVRQTFNKEIKTMKK EEEHHHCHHHHHHHH	57.54	29967540
253	O-linked_Glycosylation	TFNKEIKTMKKFESP HHCHHHHHHHHCCCC	39.63	29237092
259	O-linked_Glycosylation	KTMKKFESPNILRIF HHHHHCCCCCHHHEE	26.78	29237092
302	Phosphorylation	LDREKDLTLGKRMVL HHHHCCCCHHHHHHH	43.53	-
331	Ubiquitination	EAPELHGKIRSSNFL CCHHHCCEEECCCEE	24.97	33845483
334	Phosphorylation	ELHGKIRSSNFLVTQ HHCCEEECCCEEEEC	32.86	-
354	Acetylation	LAGFELRKTQTSMSL ECCEEEECCCCCCCC	58.57	7377595
354	Ubiquitination	LAGFELRKTQTSMSL ECCEEEECCCCCCCC	58.57	24816145
357	Phosphorylation	FELRKTQTSMSLGTT EEEECCCCCCCCCCC	31.46	22265413
357	O-linked_Glycosylation	FELRKTQTSMSLGTT EEEECCCCCCCCCCC	31.46	29237092
358	O-linked_Glycosylation	ELRKTQTSMSLGTTR EEECCCCCCCCCCCH	9.14	29237092
358	Phosphorylation	ELRKTQTSMSLGTTR EEECCCCCCCCCCCH	9.14	22265413
360	Phosphorylation	RKTQTSMSLGTTREK ECCCCCCCCCCCHHH	24.34	-
364	Phosphorylation	TSMSLGTTREKTDRV CCCCCCCCHHHCHHC	34.72	-
367	Ubiquitination	SLGTTREKTDRVKST CCCCCHHHCHHCCCC	53.05	22817900
372	Ubiquitination	REKTDRVKSTAYLSP HHHCHHCCCCEECCH	42.87	21963094
373	Phosphorylation	EKTDRVKSTAYLSPQ HHCHHCCCCEECCHH	18.53	23663014
374	Phosphorylation	KTDRVKSTAYLSPQE HCHHCCCCEECCHHH	17.38	19276368
376	Phosphorylation	DRVKSTAYLSPQELE HHCCCCEECCHHHHH	14.06	23663014
378	Phosphorylation	VKSTAYLSPQELEDV CCCCEECCHHHHHHH	16.32	23663014
387	Phosphorylation	QELEDVFYQYDVKSE HHHHHHHHHCCCCHH	13.15	26074081
389	Phosphorylation	LEDVFYQYDVKSEIY HHHHHHHCCCCHHEE	16.01	26074081
393	Phosphorylation	FYQYDVKSEIYSFGI HHHCCCCHHEEEEEE	29.13	26074081
396	Phosphorylation	YDVKSEIYSFGIVLW CCCCHHEEEEEEEEE	8.22	26074081
397	Phosphorylation	DVKSEIYSFGIVLWE CCCHHEEEEEEEEEE	23.74	26074081
407	Phosphorylation	IVLWEIATGDIPFQG EEEEEHHCCCCCCCC	40.84	26074081
417	Phosphorylation	IPFQGCNSEKIRKLV CCCCCCCHHHHHHHH	44.32	26074081
454	Phosphorylation	ECRAHDPSVRPSVDE HHHHCCCCCCCCHHH	36.49	20873877
458	Phosphorylation	HDPSVRPSVDEILKK CCCCCCCCHHHHHHH	31.47	20873877
467	Phosphorylation	DEILKKLSTFSK--- HHHHHHHHCCCC---	35.96	23312004
468	Phosphorylation	EILKKLSTFSK---- HHHHHHHCCCC----	42.22	23312004
470	Phosphorylation	LKKLSTFSK------ HHHHHCCCC------	37.23	23312004

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
357	T	Phosphorylation	Kinase	RIPK3	Q9Y572	Uniprot
358	S	Phosphorylation	Kinase	RIPK3	Q9Y572	Uniprot
360	S	Phosphorylation	Kinase	RIPK3	Q9Y572	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of MLKL_HUMAN !!

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 MLKL_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NDUB7_HUMAN	NDUFB7	physical	21988832
RAD18_HUMAN	RAD18	physical	21988832
THOC3_HUMAN	THOC3	physical	21988832
CASP8_HUMAN	CASP8	physical	26496610
GSLG1_HUMAN	GLG1	physical	26496610
SRA1_HUMAN	SRA1	physical	26496610
PAR16_HUMAN	PARP16	physical	26496610
LRCH3_HUMAN	LRCH3	physical	26496610
TRAF2_HUMAN	TRAF2	physical	25882049
RIPK1_HUMAN	RIPK1	physical	27560715
RIPK3_HUMAN	RIPK3	physical	27560715

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
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of MLKL_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe kinome across the cell cycle."; Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,Greff Z., Keri G., Stemmann O., Mann M.; Mol. Cell 31:438-448(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND MASSSPECTROMETRY.	18691976 [Abstract]