Protein detail

MLKL

Mixed lineage kinase domain-like protein (hMLKL)

Protein symbol MLKL	UniProt ID Q8NB16	EVMP score 0.50
Frequency 2	Transmembrane count	Protein classification

EVMP score: annotation confidence score.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information

Protein Names

Mixed lineage kinase domain-like protein (hMLKL)

Protein Function

Enzymes
Transporters:Transporter channels and pores
Kinases
Predicted intracellular proteins

Ensembl

ENSG00000168404

Entrez Gene Symbol

MLKL

Frequency

EVMP Score

0.50

Fluorescence & Localization

Function & Pathway

Protein Function

Enzymes
Transporters:Transporter channels and pores
Kinases
Predicted intracellular proteins

Cellular Component

Molecular Function

Biological Process

KEGG

Reactome

Mediation Categories

Clinical-translation mediationFusion and delivery mediation

Relations & Evidence

Enzyme-Mediated Modification

8 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
MLKL	RIPK3	Q9Y572	S	358	phosphorylation	Sparser_ProtMapperSIGNORProtMapperRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:24434512 ProtMapper:26024392 ProtMapper:27941671 ProtMapper:29026104 ProtMapper:24901049 ProtMapper:26184911 ProtMapper:28126382 ProtMapper:25493335 ProtMapper:27959630 ProtMapper:28807105 ProtMapper:27826146 ProtMapper:27832137 ProtMapper:29484439 SIGNOR:24012422 ProtMapper:26967968
MLKL	RIPK3	Q9Y572	T	357	phosphorylation	Sparser_ProtMapperSIGNORProtMapperRLIMS-P_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:26866270 ProtMapper:24434512 ProtMapper:27941671 ProtMapper:22265413 ProtMapper:26184911 ProtMapper:24703947 ProtMapper:28126382 ProtMapper:25493335 ProtMapper:27959630 SIGNOR:24012422 ProtMapper:29484439
MLKL	RIPK3	Q9Y572	S	360	phosphorylation	SIGNOR	SIGNOR:24012422
MLKL	TYRO3	Q06418	Y	376	phosphorylation	PhosphoSite
MLKL	MERTK	Q12866	Y	376	phosphorylation	PhosphoSite
MLKL	AXL	P30530	Y	376	phosphorylation	PhosphoSite
MLKL	MPRIP	Q6WCQ1	T	357	phosphorylation	REACH_ProtMapperSparser_ProtMapperProtMapper	ProtMapper:26866270 ProtMapper:27033670 ProtMapper:22265413 ProtMapper:30062059 ProtMapper:24703947 ProtMapper:23886067 ProtMapper:26938298 ProtMapper:26704887 ProtMapper:25714887 ProtMapper:24587805
MLKL	MPRIP	Q6WCQ1	S	358	phosphorylation	REACH_ProtMapperSparser_ProtMapperProtMapper	ProtMapper:25858093 ProtMapper:26866270 ProtMapper:27033670 ProtMapper:22265413 ProtMapper:30062059 ProtMapper:24703947 ProtMapper:23886067 ProtMapper:26938298 ProtMapper:30029665 ProtMapper:26704887 ProtMapper:25714887 ProtMapper:24587805

Ligand-Receptor Signaling

9 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	OmniPath	No	Yes	No	No	No
intracellular	intracellular	LOCATE	No	No	No	No	No
intracellular	intracellular	ComPPI	No	No	No	No	No
intracellular	intracellular	GO_Intercell	No	No	No	No	No
intracellular	intracellular	UniProt_location	No	No	No	No	No
intracellular	intracellular	OmniPath	No	No	No	No	No
plasma_membrane	plasma_membrane	UniProt_location	No	No	No	No	No
plasma_membrane	plasma_membrane	OmniPath	No	No	No	No	No
receptor	receptor	scConnect	No	Yes	No	No	No

Regulatory Interaction Network

5 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
MERTK	Q12866	MLKL	Q8NB16	Yes	Yes	No	SIGNORPhosphoSite_ProtMapperProtMapper	SIGNOR:31230815
RIPK3	Q9Y572	MLKL	Q8NB16	Yes	Yes	No	Sparser_ProtMapperiPTMnetSIGNORProtMapperRLIMS-P_ProtMapperHINTIntActInnateDBSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	ProtMapper:26866270 ProtMapper:32457484 ProtMapper:27941671 ProtMapper:29066276 ProtMapper:31285421 PhosphoSite:30029665 HINT:22265413 SIGNOR:24012422 ProtMapper:33392484 HINT:24316671 InnateDB:23612963 ProtMapper:27959630 ProtMapper:30050058 ProtMapper:30140326 ProtMapper:26967968 ProtMapper:24434512 ProtMapper:24901049 ProtMapper:26184911 HINT:22265414 ProtMapper:24703947 PhosphoSite:26184911 ProtMapper:28126382 ProtMapper:30541583 ProtMapper:25493335 ProtMapper:31779177 ProtMapper:31766571 HINT:34811356 ProtMapper:27826146 ProtMapper:27832137 ProtMapper:29484439 ProtMapper:34811356 ProtMapper:32522477 ProtMapper:26024392 ProtMapper:22265413 ProtMapper:29026104 ProtMapper:31164887 ProtMapper:33503908 ProtMapper:29598451 PhosphoSite:24703947 ProtMapper:24012422 PhosphoSite:34689152 IntAct:22265413 ProtMapper:28807105
TYRO3	Q06418	MLKL	Q8NB16	Yes	Yes	No	SIGNORPhosphoSitePhosphoSite_ProtMapperProtMapper	SIGNOR:31230815 PhosphoSite:31230815
MLKL	Q8NB16	CNR2	P34972	Yes	No	Yes	SIGNOR	SIGNOR:10400664 SIGNOR:36448459
UFO	P30530	MLKL	Q8NB16	Yes	Yes	No	SIGNORPhosphoSite_ProtMapperProtMapper	SIGNOR:31230815

Protein Complex Composition

2 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
	MLKL	Q8NB16	2	PDB	PDB:6zvoPDB:7jxuPDB:6o5zPDB:6zz1PDB:5knj
	MLKL RIPK3	Q8NB16 Q9Y572	1:1	PDB	PDB:7mon

Isolation & Detection Technology

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion ChromatographyImmunoaffinity Capture	Mass spectrometry	5	38113368 41307968 38207106 32854315 37926756

Sequence, Structure & Domains

Sequences

Length

471

Mass

54,479

Sequence

MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQDQGKRSVPSEKLTTAMNRFKAALEEANGEIEKFSNRSNICRFLTASQDKILFKDVNRKLSDVWKELSLLLQVEQRMPVSPISQGASWAQEDQQDADEDRRAFQMLRRDNEKIEASLRRLEINMKEIKETLRQYLPPKCMQEIPQEQIKEIKKEQLSGSPWILLRENEVSTLYKGEYHRAPVAIKVFKKLQAGSIAIVRQTFNKEIKTMKKFESPNILRIFGICIDETVTPPQFSIVMEYCELGTLRELLDREKDLTLGKRMVLVLGAARGLYRLHHSEAPELHGKIRSSNFLVTQGYQVKLAGFELRKTQTSMSLGTTREKTDRVKSTAYLSPQELEDVFYQYDVKSEIYSFGIVLWEIATGDIPFQGCNSEKIRKLVAVKRQQEPLGEDCPSELREIIDECRAHDPSVRPSVDEILKKLSTFSK

Alternative Products

Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q8NB16-1; Sequence=Displayed; Name=2; IsoId=Q8NB16-2; Sequence=VSP_052133, VSP_052134

Alternative Sequence

179..205; YLPPKCMQEIPQEQIKEIKKEQLSGSP -> SLESSSGKSPLEISRFKVKNVKTGSAS (in isoform 2); 206..413; Missing (in isoform 2)

3D Structural Models

Turn

128..132; 360..362; 411..414

Helix

2..20; 25..46; 56..79; 82..90; 99..120; 133..148; 198..201; 240..256; 291..297; 303..322; 334..336; 353..359; 373..376; 379..383; 391..407; 417..425; 439..448; 453..455; 459..467

Beta Strand

22..24; 93..96; 202..204; 207..211; 213..222; 225..232; 265..271; 274..276; 278..284; 323..325; 337..339; 345..347; 349..352; 435..437

3D Structure

NMR spectroscopy (7); X-ray crystallography (15)

Domain & Motif Annotations

Coiled Coil

55..84; 139..180

Domain (CC)

The protein kinase domain is catalytically inactive but contains an unusual pseudoactive site with an interaction between Lys-230 and Gln-356 residues (By similarity). Upon phosphorylation by RIPK3, undergoes an active conformation (By similarity).; DOMAIN: The coiled coil region 2 is responsible for homotrimerization.

Domain (FT)

194..469; Protein kinase

Region

1..149; N-terminal bundle and brace (NBB); mediates INSP6 binding

Protein Families

Protein kinase superfamily

Sequence Similarities

Belongs to the protein kinase superfamily.

Clinical Relevance

Drugs

MLKL COMPOUND 1 COMPOUND 56 [PMID: 36136378]

Interaction Protein

ENSG00000129465

Interaction Count

Interaction Dataset

intact_biogrid