MLKL (mixed lineage kinase domain like pseudokinase)

Gene

• Entrez ID: 197259
• Gene name: Mixed lineage kinase domain like pseudokinase
• Gene symbol: MLKL
• Synonyms: hMLKL
• Chromosome: 16
• Chromosome location: 16q23.1
• Summary: This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to be inactive because it lacks several residues required for activity. This protein plays a critical role in tumor necrosi

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1151088	hsa-miR-1587	CLIP-seq
MIRT1151089	hsa-miR-3147	CLIP-seq
MIRT1151090	hsa-miR-3201	CLIP-seq
MIRT1151091	hsa-miR-4422	CLIP-seq
MIRT1151092	hsa-miR-4496	CLIP-seq
MIRT1151093	hsa-miR-4674	CLIP-seq
MIRT1151094	hsa-miR-4712-3p	CLIP-seq
MIRT1151095	hsa-miR-4716-5p	CLIP-seq
MIRT1151096	hsa-miR-4781-3p	CLIP-seq
MIRT1151097	hsa-miR-4791	CLIP-seq
MIRT1151098	hsa-miR-617	CLIP-seq
MIRT2272585	hsa-miR-578	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004672	Function	Protein kinase activity	IBA	21873635
GO:0004672	Function	Protein kinase activity	ISS
GO:0004706	Function	JUN kinase kinase kinase activity	IBA	21873635
GO:0005515	Function	Protein binding	IPI	22265413, 22265414, 29883609
GO:0005524	Function	ATP binding	IDA	24219132
GO:0005634	Component	Nucleus	ISS
GO:0005737	Component	Cytoplasm	IDA	24316671
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	24316671, 29883610
GO:0006468	Process	Protein phosphorylation	IEA
GO:0007166	Process	Cell surface receptor signaling pathway	IEA
GO:0007256	Process	Activation of JNKK activity	IEA
GO:0007257	Process	Activation of JUN kinase activity	IBA	21873635
GO:0019901	Function	Protein kinase binding	IEA
GO:0030054	Component	Cell junction	IDA
GO:0044877	Function	Protein-containing complex binding	IDA	22265414
GO:0051607	Process	Defense response to virus	ISS
GO:0070207	Process	Protein homotrimerization	IDA	24316671
GO:0070266	Process	Necroptotic process	IMP	22265414, 24316671, 29883610
GO:0070266	Process	Necroptotic process	TAS
GO:0097527	Process	Necroptotic signaling pathway	IMP	22265413
GO:0097528	Process	Execution phase of necroptosis	ISS

Other IDs

• MIM: 615153
• HGNC: 26617
• e!Ensembl: ENSG00000168404

Protein

• UniProt ID: Q8NB16
• Protein name: Mixed lineage kinase domain-like protein (hMLKL)
• Protein function: Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Does not have protein kinase activity (PubMed:22265413, PubMed:22265414, PubMed:
• PDB: 2MSV, 4M67, 4MWI, 5KNJ, 5KO1, 6BWK, 6D74, 6LK5, 6LK6, 6O5Z, 6UX8, 6ZLE, 6ZPR, 6ZVO, 6ZZ1, 7JW7, 7JXU, 7MON, 7NM2, 7NM4, 7NM5, 8SLZ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07714	PK_Tyr_Ser-Thr	209 → 466	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQDQGKRSVPSEKLTT
  AMNRFKAALEEANGEIEKFSNRSNICRFLTASQDKILFKDVNRKLSDVWKELSLLLQVEQ
  RMPVSPISQGASWAQEDQQDADEDRRAFQMLRRDNEKIEASLRRLEINMKEIKETLRQYL
  PPKCMQEIPQEQIKEIKKEQLSGSPWILLRENEVSTLYKGEYHRAPVAIKVFKKLQAGSI
  AIVRQTFNKEIKTMKKFESPNILRIFGICIDETVTPPQFSIVMEYCELGTLRELLDREKD
  LTLGKRMVLVLGAARGLYRLHHSEAPELHGKIRSSNFLVTQGYQVKLAGFELRKTQTSMS
  LGTTREKTDRVKSTAYLSPQELEDVFYQYDVKSEIYSFGIVLWEIATGDIPFQGCNSEKI
  RKLVAVKRQQEPLGEDCPSELREIIDECRAHDPSVRPSVDEILKKLSTFSK

• Sequence length: 471

Pathways

KEGG:

Necroptosis
Cytosolic DNA-sensing pathway
TNF signaling pathway
Salmonella infection

Reactome:

TRP channels
RIPK1-mediated regulated necrosis

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Gastric cancer	Gastric Adenocarcinoma	rs137854571, rs63751108, rs34612342, rs121908383, rs121909144, rs121909775, rs121909219, rs121909223, rs63750871, rs80359530, rs121964873, rs121913530, rs606231203, rs121918505, rs587776802, rs28933369, rs121912469, rs80358011, rs397507262, rs80359439, rs397507333, rs80359543, rs80358831, rs80359596, rs80358920, rs80358972, rs80359659, rs397507404, rs397514661, rs80359516, rs200495564, rs80358419, rs80359274, rs80359283, rs80358427, rs80358428, rs80358435, rs81002805, rs397507660, rs397507663, rs80359391, rs80359443, rs81002797, rs80359466, rs397507752, rs80359484, rs80359603, rs397507954, rs80359058, rs80359071, rs397507981, rs80359121, rs80357086, rs80357064, rs397508936, rs80357695, rs80357661, rs397509035, rs80357544, rs80357577, rs80357881, rs80357296, rs80356923, rs80356866, rs80357504, rs80357390, rs80357239, rs80358099, rs397509284, rs80357258, rs199474738, rs199474747, rs587779204, rs63750439, rs267608076, rs587779246, rs63749999, rs267608078, rs63751327, rs267607719, rs267607734, rs63750706, rs63751711, rs587779047, rs587779075, rs267607949, rs63750633, rs63750803, rs63751618, rs267608154, rs200640585, rs80358018, rs80357857, rs80357882, rs180177103, rs587779815, rs587779865, rs587779872, rs587780059, rs121912666, rs587780088, rs587780104, rs200432447, rs180177100, rs587780226, rs587780784, rs587776416, rs587781276, rs587781629, rs587781694, rs587781727, rs587781730, rs587781807, rs587781894, rs587781948, rs121913344, rs587782292, rs587782350, rs587782558, rs587782719, rs587782885, rs587783057, rs730881833, rs730881411, rs730881336, rs139770721, rs730881869, rs730881633, rs730882007, rs786203115, rs765123255, rs1553333738, rs762083530, rs786202800, rs17174393, rs55996097, rs750621215, rs786203451, rs747604569, rs764389018, rs786204433, rs786204862, rs772821016, rs779582317, rs863225406, rs193922343, rs759965045, rs63749919, rs760228510, rs746481984, rs762307622, rs876659736, rs876660933, rs747727055, rs1450394308, rs876658348, rs876658431, rs876659326, rs876660444, rs730881369, rs878853865, rs753862052, rs587780024, rs138941496, rs886040739, rs886040744, rs886040347, rs878854957, rs886040123, rs398122662, rs886040942, rs1057517104, rs1057516320, rs1057516683, rs879254046, rs1057517253, rs587781927, rs985033810, rs1057519989, rs775464903, rs374230313, rs758304323, rs1060501599, rs758081262, rs1060500126, rs1060502734, rs587776408, rs1060501695, rs1114167816, rs1114167596, rs1114167667, rs1555460315, rs1135402788, rs1554086196, rs730881919, rs773356478, rs769237459, rs1553653158, rs587782087, rs1555107263, rs1555119940, rs1403784434, rs1342519012, rs751710099, rs1553616361, rs1553619721, rs1270783041, rs775036118, rs1555288557, rs1555460548, rs1555461154, rs1298667185, rs1553622218, rs63751101, rs1349928568, rs771936821, rs1021662947, rs1555921011, rs81002831, rs1555124506, rs1555574803, rs1060502716, rs1555605362, rs747057367, rs1565385010, rs1567554500, rs1567516230, rs1558644995, rs1555591308, rs778306619, rs1566231194, rs1603328466, rs1570406302, rs1586108714, rs768362387, rs1597713777, rs1060502926, rs1597867185, rs1591517571, rs1591663236, rs1593903006, rs1555284779, rs1597096243, rs45459799, rs1597360340, rs587781905, rs864622481, rs1601753141, rs1966858562, rs1966967065, rs1967016153, rs1967113484, rs2080473458, rs1591387978, rs1224428422, rs1597747184, rs2082309297, rs2051929740, rs147542208