MLKL

Functionⁱ

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 (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (PubMed:29883610).5 Publications

Miscellaneous

Interaction with RIPK3 is species specific: human MLKL only interacts with human RIPK3 and not mouse RIPK3.1 Publication

Activity regulationⁱ

Activated via binding to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which mediates the release of an N-terminal auto-inhibitory region. Activation requires not only RIPK3-dependent phosphorylation but also binding to highly phosphorylated inositol phosphates (PubMed:29883610). Inhibited by necrosulfonamide, a specific inhibitor of necroptosis that targets Cys-86.2 Publications

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	86	Target of necrosulfonamide inhibitor		1
Binding siteⁱ	230	ATPCurated		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	209 – 217	ATPPROSITE-ProRule annotation		9

GO - Molecular functionⁱ

ATP binding
Source: UniProtKB
Inferred from direct assayⁱ
- 24219132
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- 24316671
JUN kinase kinase kinase activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
protein-containing complex binding
Source: UniProtKB
Inferred from direct assayⁱ
- 22265414
protein kinase binding Source: Ensembl
protein serine/threonine kinase activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of JUN kinase activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cell surface receptor signaling pathway Source: InterPro
MAPK cascade
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
necroptotic process
Source: UniProtKB
Inferred from mutant phenotypeⁱ
protein homotrimerization
Source: UniProtKB
Inferred from direct assayⁱ
- 24316671

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Biological process	Necrosis
Ligand	ATP-binding, Nucleotide-binding

Enzyme and pathway databases

Reactomeⁱ	R-HSA-3295583 TRP channels R-HSA-5213460 RIPK1-mediated regulated necrosis

Reactomeⁱ

R-HSA-3295583 TRP channels
R-HSA-5213460 RIPK1-mediated regulated necrosis

Protein family/group databases

TCDBⁱ	1.A.105.1.1 the mixed lineage kinase domain-like (mlkl) family

TCDBⁱ

1.A.105.1.1 the mixed lineage kinase domain-like (mlkl) family

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Mixed lineage kinase domain-like protein Short name: hMLKL
Gene namesⁱ	Name:MLKLImported
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 16

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000168404.12
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:26617 MLKL
MIMⁱ	615153 gene
neXtProtⁱ	NX_Q8NB16

Keywords - Cellular componentⁱ

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	58	L → G: Does not affect formation of homotrimers, while translocation to the plasma membrane on necroptosis induction is impaired; when associated with G-76. 1 Publication	1
Mutagenesisⁱ	76	I → G: Does not affect formation of homotrimers, while translocation to the plasma membrane on necroptosis induction is impaired; when associated with G-58. 1 Publication	1
Mutagenesisⁱ	86	C → S: Abolishes binding to necrosulfonamide inhibitor. 1 Publication	1
Mutagenesisⁱ	162	L → G: Impairs formation of homotrimers and translocation to the plasma membrane on necroptosis induction; when associated with G-165. 1 Publication	1
Mutagenesisⁱ	165	L → G: Impairs formation of homotrimers and translocation to the plasma membrane on necroptosis induction; when associated with G-162. 1 Publication	1
Mutagenesisⁱ	230	K → M: Abolishes ATP-binding. 1 Publication	1
Mutagenesisⁱ	331	K → N: Impairs ATP-binding. 1 Publication	1
Mutagenesisⁱ	351	E → K: Binds ATP with an enhanced affinity. 1 Publication	1
Mutagenesisⁱ	357 – 358	TS → ED: Mimics phosphorylation state; acts as a dominant-negative mutant that impairs necroptosis.	2
Mutagenesisⁱ	357	T → A: No effect. Abolishes ability to mediate necroptosis; when associated with A-358. 1 Publication	1
Mutagenesisⁱ	358	S → A: No effect. Abolishes ability to mediate necroptosis; when associated with A-357. 1 Publication	1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	197259
Open Targets More...OpenTargetsⁱ	ENSG00000168404
PharmGKBⁱ	PA142671349

Chemistry databases

ChEMBLⁱ	CHEMBL1938217
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2106

Polymorphism and mutation databases

BioMutaⁱ	MLKL
DMDMⁱ	74762545

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000248239	1 – 471	Mixed lineage kinase domain-like proteinAdd BLAST		471

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	125	PhosphoserineCombined sources	1
Modified residueⁱ	357	Phosphothreonine; by RIPK31 Publication	1
Modified residueⁱ	358	Phosphoserine; by RIPK32 Publications	1
Modified residueⁱ	360	Phosphoserine; by RIPK3By similarity	1

Post-translational modificationⁱ

Phosphorylation by RIPK3 induces a conformational switch that is required for necroptosis. It also induces homotrimerization and localization to the plasma membrane.1 Publication

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

EPDⁱ	Q8NB16
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q8NB16
PaxDbⁱ	Q8NB16
PeptideAtlas More...PeptideAtlasⁱ	Q8NB16
PRIDEⁱ	Q8NB16
ProteomicsDBⁱ	72718 72719 [Q8NB16-2]

PTM databases

iPTMnetⁱ	Q8NB16
PhosphoSitePlusⁱ	Q8NB16

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000168404 Expressed in 184 organ(s), highest expression level in blood
CleanExⁱ	HS_MLKL
ExpressionAtlasⁱ	Q8NB16 baseline and differential
Genevisibleⁱ	Q8NB16 HS

Interactionⁱ

Subunit structureⁱ

Homooligomer (PubMed:29883610). Homotrimer; forms homotrimers on necroptosis induction. Interacts with RIPK3; the interaction is direct. Upon TNF-induced necrosis, forms in complex with PGAM5, RIPK1 and RIPK3. Within this complex, may play a role in the proper targeting of RIPK1/RIPK3 to its downstream effector PGAM5.6 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
RIPK3	Q9Y572	10	EBI-1055040,EBI-298250

With

Entry

#Exp.

IntAct

Notes

RIPK3

Q9Y572

10

EBI-1055040,EBI-298250

GO - Molecular functionⁱ

identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- 24316671
protein kinase binding Source: Ensembl

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	128244, 16 interactors
Database of interacting proteins More...DIPⁱ	DIP-41782N
IntActⁱ	Q8NB16, 15 interactors
Molecular INTeraction database More...MINTⁱ	Q8NB16
STRINGⁱ	9606.ENSP00000308351

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	4 – 19	Combined sources	16
Beta strandⁱ	22 – 24	Combined sources	3
Helixⁱ	25 – 45	Combined sources	21
Turnⁱ	46 – 48	Combined sources	3
Helixⁱ	56 – 78	Combined sources	23
Helixⁱ	82 – 91	Combined sources	10
Beta strandⁱ	93 – 96	Combined sources	4
Helixⁱ	99 – 119	Combined sources	21
Turnⁱ	128 – 132	Combined sources	5
Helixⁱ	133 – 150	Combined sources	18
Helixⁱ	198 – 201	Combined sources	4
Beta strandⁱ	202 – 204	Combined sources	3
Beta strandⁱ	207 – 211	Combined sources	5
Beta strandⁱ	213 – 222	Combined sources	10
Beta strandⁱ	225 – 232	Combined sources	8
Helixⁱ	240 – 256	Combined sources	17
Beta strandⁱ	265 – 271	Combined sources	7
Beta strandⁱ	274 – 276	Combined sources	3
Beta strandⁱ	278 – 284	Combined sources	7
Helixⁱ	291 – 297	Combined sources	7
Helixⁱ	303 – 322	Combined sources	20
Beta strandⁱ	323 – 325	Combined sources	3
Helixⁱ	334 – 336	Combined sources	3
Beta strandⁱ	337 – 339	Combined sources	3
Beta strandⁱ	345 – 347	Combined sources	3
Helixⁱ	373 – 376	Combined sources	4
Helixⁱ	379 – 383	Combined sources	5
Helixⁱ	391 – 407	Combined sources	17
Turnⁱ	411 – 414	Combined sources	4
Helixⁱ	417 – 425	Combined sources	9
Helixⁱ	439 – 448	Combined sources	10
Helixⁱ	453 – 455	Combined sources	3
Helixⁱ	459 – 467	Combined sources	9

Show more details

3D structure databases

ProteinModelPortalⁱ	Q8NB16
SMRⁱ	Q8NB16
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	194 – 469	Protein kinasePROSITE-ProRule annotationAdd BLAST		276

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	1 – 149	N-terminal bundle and brace (NBB); mediates INSP6 binding1 PublicationAdd BLAST		149

Coiled coil

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Coiled coilⁱ	55 – 84	Sequence analysisAdd BLAST		30
Coiled coilⁱ	139 – 180	Sequence analysisAdd BLAST		42

Domainⁱ

The protein kinase domain is catalytically inactive but contains an unusual pseudoactive site with an interaction between Lys-230 and Gln-356 residues. Upon phosphorylation by RIPK3, undergoes an active conformation (By similarity).By similarity

The coiled coil region 2 is responsible for homotrimerization.1 Publication

Sequence similaritiesⁱ

Belongs to the protein kinase superfamily.Curated

Keywords - Domainⁱ

Coiled coil

Phylogenomic databases

eggNOGⁱ	KOG0192 Eukaryota COG0515 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000016453
HOGENOMⁱ	HOG000113601
HOVERGENⁱ	HBG056156
InParanoidⁱ	Q8NB16
KEGG Orthology (KO) More...KOⁱ	K08849
OMAⁱ	WQQEDQQ
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G05XI
PhylomeDBⁱ	Q8NB16
TreeFamⁱ	TF328453

Family and domain databases

Gene3Dⁱ	1.20.930.20, 1 hit
InterProⁱ	View protein in InterPro IPR036537 Adaptor_Cbl_N_dom_sf IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR001245 Ser-Thr/Tyr_kinase_cat_dom
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF07714 Pkinase_Tyr, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show all Align All

Isoform 12 Publications (identifier: Q8NB16-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MENLKHIITL GQVIHKRCEE MKYCKKQCRR LGHRVLGLIK PLEMLQDQGK 
        60         70         80         90        100
RSVPSEKLTT AMNRFKAALE EANGEIEKFS NRSNICRFLT ASQDKILFKD 
       110        120        130        140        150
VNRKLSDVWK ELSLLLQVEQ RMPVSPISQG ASWAQEDQQD ADEDRRAFQM 
       160        170        180        190        200
LRRDNEKIEA SLRRLEINMK EIKETLRQYL PPKCMQEIPQ EQIKEIKKEQ 
       210        220        230        240        250
LSGSPWILLR ENEVSTLYKG EYHRAPVAIK VFKKLQAGSI AIVRQTFNKE 
       260        270        280        290        300
IKTMKKFESP NILRIFGICI DETVTPPQFS IVMEYCELGT LRELLDREKD 
       310        320        330        340        350
LTLGKRMVLV LGAARGLYRL HHSEAPELHG KIRSSNFLVT QGYQVKLAGF 
       360        370        380        390        400
ELRKTQTSMS LGTTREKTDR VKSTAYLSPQ ELEDVFYQYD VKSEIYSFGI 
       410        420        430        440        450
VLWEIATGDI PFQGCNSEKI RKLVAVKRQQ EPLGEDCPSE LREIIDECRA 
       460        470 
HDPSVRPSVD EILKKLSTFS K

Length:471

Mass (Da):54,479

Last modified:October 1, 2002 - v1

Checksum:ⁱ005E7F7AB6D20649

GO

Isoform 21 Publication (identifier: Q8NB16-2) [UniParc]FASTA Add to basket

The sequence of this isoform differs from the canonical sequence as follows:
179-205: YLPPKCMQEIPQEQIKEIKKEQLSGSP → SLESSSGKSPLEISRFKVKNVKTGSAS
206-413: Missing.

« Hide

        10         20         30         40         50
MENLKHIITL GQVIHKRCEE MKYCKKQCRR LGHRVLGLIK PLEMLQDQGK 
        60         70         80         90        100
RSVPSEKLTT AMNRFKAALE EANGEIEKFS NRSNICRFLT ASQDKILFKD 
       110        120        130        140        150
VNRKLSDVWK ELSLLLQVEQ RMPVSPISQG ASWAQEDQQD ADEDRRAFQM 
       160        170        180        190        200
LRRDNEKIEA SLRRLEINMK EIKETLRQSL ESSSGKSPLE ISRFKVKNVK 
       210        220        230        240        250
TGSASGCNSE KIRKLVAVKR QQEPLGEDCP SELREIIDEC RAHDPSVRPS 
       260 
VDEILKKLST FSK

Note: No experimental confirmation available.Curated

Show »

Length:263

Mass (Da):30,279

Checksum:ⁱ183FD0023D8A1EC3

GO

Computationally mapped potential isoform sequencesⁱ

There are 4 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

I3L2T9	I3L2T9_HUMAN	Mixed lineage kinase domain-like pr... Mixed lineage kinase domain-like protein	MLKL	211	Annotation score:
I3L4Z5	I3L4Z5_HUMAN	Mixed lineage kinase domain-like pr... Mixed lineage kinase domain-like protein	MLKL	62	Annotation score:
I3L4A6	I3L4A6_HUMAN	Mixed lineage kinase domain-like pr... Mixed lineage kinase domain-like protein	MLKL	175	Annotation score:
I3L2U3	I3L2U3_HUMAN	Mixed lineage kinase domain-like pr... Mixed lineage kinase domain-like protein	MLKL	102	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_041350	52	S → T1 PublicationCorresponds to variant dbSNP:rs34251827Ensembl.	1
Natural variantⁱVAR_041351	100	D → E1 PublicationCorresponds to variant dbSNP:rs33987771Ensembl.	1
Natural variantⁱVAR_041352	132	S → P1 PublicationCorresponds to variant dbSNP:rs35589326Ensembl.	1
Natural variantⁱVAR_041353	146	R → Q1 PublicationCorresponds to variant dbSNP:rs34515646Ensembl.	1
Natural variantⁱVAR_041354	169	M → L1 PublicationCorresponds to variant dbSNP:rs55929310Ensembl.	1
Natural variantⁱVAR_041355	291	L → P in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1313508921Ensembl.	1
Natural variantⁱVAR_041356	364	T → M1 PublicationCorresponds to variant dbSNP:rs34389205Ensembl.	1
Natural variantⁱVAR_041357	398	F → I in a gastric adenocarcinoma sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_041358	421	R → H1 PublicationCorresponds to variant dbSNP:rs55987292Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_052133	179 – 205	YLPPK…LSGSP → SLESSSGKSPLEISRFKVKN VKTGSAS in isoform 2. 1 PublicationAdd BLAST		27
Alternative sequenceⁱVSP_052134	206 – 413	Missing in isoform 2. 1 PublicationAdd BLAST		208

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AK091708 mRNA Translation: BAC03728.1 AC109599 Genomic DNA No translation available. BC028141 mRNA Translation: AAH28141.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS32487.1 [Q8NB16-1] CCDS45528.1 [Q8NB16-2]
NCBI Reference Sequences More...RefSeqⁱ	NP_001135969.1, NM_001142497.2 [Q8NB16-2] NP_689862.1, NM_152649.3 [Q8NB16-1] XP_005255891.1, XM_005255834.3 [Q8NB16-1]
UniGeneⁱ	Hs.119878

Genome annotation databases

Ensemblⁱ	ENST00000306247; ENSP00000303118; ENSG00000168404 [Q8NB16-2] ENST00000308807; ENSP00000308351; ENSG00000168404 [Q8NB16-1]
GeneIDⁱ	197259
KEGGⁱ	hsa:197259
UCSC genome browser More...UCSCⁱ	uc002fdb.3 human [Q8NB16-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q8NB16	Mixed lineage kinase domain-like protein (Fragment)		HUMAN		62	UniRef100_Q8NB16
MLKL isoform 3 (Fragment)		PANTR		62
Mixed lineage kinase domain-like protein (Fragment)		HUMAN		211
MLKL isoform 1 (Fragment)		PANTR		211
UPI0003B7E088		HUMAN		293

Protein	Similar proteins		Species	Score	Length	Source
Q8NB16	Mixed lineage kinase domain-like protein (Fragment)		HUMAN		62	UniRef90_Q8NB16
MLKL isoform 3 (Fragment)		PANTR		62
Uncharacterized protein		RHIBE		478
Uncharacterized protein		CERAT		477
MLKL isoform 4		PONAB		471
+28
Q8NB16-2	MLKL isoform 4		PANTR		263	UniRef90_Q8NB16-2
Uncharacterized protein		PANPA		263
MLKL isoform 1		PONAB		263

Protein	Similar proteins		Species	Score	Length	Source
Q8NB16	Mixed lineage kinase domain-like protein (Fragment)		HUMAN		62	UniRef50_Q8NB16
MLKL isoform 3 (Fragment)		PANTR		62
Uncharacterized protein		RHIBE		478
Uncharacterized protein		CERAT		477
MLKL isoform 4		PONAB		471
+38
Q8NB16-2	MLKL isoform 1		PONAB		263	UniRef50_Q8NB16-2
MLKL isoform 4		PANTR		263
Uncharacterized protein		PANPA		263
Uncharacterized protein		PROCO		262
Uncharacterized protein		Cebus capucinus imitator		257
+6

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AK091708 mRNA Translation: BAC03728.1 AC109599 Genomic DNA No translation available. BC028141 mRNA Translation: AAH28141.1
CCDSⁱ	CCDS32487.1 [Q8NB16-1] CCDS45528.1 [Q8NB16-2]
RefSeqⁱ	NP_001135969.1, NM_001142497.2 [Q8NB16-2] NP_689862.1, NM_152649.3 [Q8NB16-1] XP_005255891.1, XM_005255834.3 [Q8NB16-1]
UniGeneⁱ	Hs.119878

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2MSV	NMR	-	A	1-154	[»]
	4M67	X-ray	1.90	A	179-471	[»]
	4MWI	X-ray	1.70	A	183-471	[»]
	5KNJ	X-ray	2.88	A/B	191-471	[»]
	5KO1	X-ray	2.16	A	191-471	[»]
	6BWK	X-ray	2.79	A	190-471	[»]
ProteinModelPortalⁱ	Q8NB16
SMRⁱ	Q8NB16
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	128244, 16 interactors
DIPⁱ	DIP-41782N
IntActⁱ	Q8NB16, 15 interactors
MINTⁱ	Q8NB16
STRINGⁱ	9606.ENSP00000308351

Chemistry databases

ChEMBLⁱ	CHEMBL1938217
GuidetoPHARMACOLOGYⁱ	2106

Protein family/group databases

TCDBⁱ	1.A.105.1.1 the mixed lineage kinase domain-like (mlkl) family

TCDBⁱ

1.A.105.1.1 the mixed lineage kinase domain-like (mlkl) family

PTM databases

iPTMnetⁱ	Q8NB16
PhosphoSitePlusⁱ	Q8NB16

Polymorphism and mutation databases

BioMutaⁱ	MLKL
DMDMⁱ	74762545

Proteomic databases

EPDⁱ	Q8NB16
MaxQBⁱ	Q8NB16
PaxDbⁱ	Q8NB16
PeptideAtlasⁱ	Q8NB16
PRIDEⁱ	Q8NB16
ProteomicsDBⁱ	72718 72719 [Q8NB16-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	197259
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000306247; ENSP00000303118; ENSG00000168404 [Q8NB16-2] ENST00000308807; ENSP00000308351; ENSG00000168404 [Q8NB16-1]
GeneIDⁱ	197259
KEGGⁱ	hsa:197259
UCSCⁱ	uc002fdb.3 human [Q8NB16-1]

Organism-specific databases

CTDⁱ	197259
DisGeNETⁱ	197259
EuPathDBⁱ	HostDB:ENSG00000168404.12
GeneCardsⁱ	MLKL
HGNCⁱ	HGNC:26617 MLKL
MIMⁱ	615153 gene
neXtProtⁱ	NX_Q8NB16
OpenTargetsⁱ	ENSG00000168404
PharmGKBⁱ	PA142671349
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0192 Eukaryota COG0515 LUCA
GeneTreeⁱ	ENSGT00390000016453
HOGENOMⁱ	HOG000113601
HOVERGENⁱ	HBG056156
InParanoidⁱ	Q8NB16
KOⁱ	K08849
OMAⁱ	WQQEDQQ
OrthoDBⁱ	EOG091G05XI
PhylomeDBⁱ	Q8NB16
TreeFamⁱ	TF328453

Enzyme and pathway databases

Reactomeⁱ	R-HSA-3295583 TRP channels R-HSA-5213460 RIPK1-mediated regulated necrosis

Reactomeⁱ

R-HSA-3295583 TRP channels
R-HSA-5213460 RIPK1-mediated regulated necrosis

Miscellaneous databases

ChiTaRSⁱ	MLKL human
GenomeRNAiⁱ	197259
Protein Ontology More...PROⁱ	PR:Q8NB16
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000168404 Expressed in 184 organ(s), highest expression level in blood
CleanExⁱ	HS_MLKL
ExpressionAtlasⁱ	Q8NB16 baseline and differential
Genevisibleⁱ	Q8NB16 HS

Family and domain databases

Gene3Dⁱ	1.20.930.20, 1 hit
InterProⁱ	View protein in InterPro IPR036537 Adaptor_Cbl_N_dom_sf IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR001245 Ser-Thr/Tyr_kinase_cat_dom
Pfamⁱ	View protein in Pfam PF07714 Pkinase_Tyr, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	MLKL_HUMAN
Accessionⁱ	Q8NB16Primary (citable) accession number: Q8NB16 Secondary accession number(s): A6NCE4, Q8N6V0
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
	Last sequence update:	October 1, 2002
	Last modified:	November 7, 2018
	This is version 147 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human and mouse protein kinases
Human and mouse protein kinases: classification and index

UniProtKB

UniParc

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UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q8NB16 (MLKL_HUMAN)

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Mixed lineage kinase domain-like protein

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Other locations

Cytosol

Plasma Membrane

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Region

Coiled coil

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ