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UniProtKB - Q8NB16 (MLKL_HUMAN)

Entry version 167 (25 May 2022)
Sequence version 1 (01 Oct 2002)
Previous versions | rss
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Protein

Mixed lineage kinase domain-like protein

Gene

MLKL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<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

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:22421439, PubMed:24316671).

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 (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671).

In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following activation by ZBP1, MLKL is phosphorylated by RIPK3 in the nucleus, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol.following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (By similarity).

Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (PubMed:29883610).

By similarity5 Publications

Miscellaneous

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

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>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 (PubMed:29883610). 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 (PubMed:22265413).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei86Target of necrosulfonamide inhibitor1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei230ATPCurated1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi209 – 217ATPPROSITE-ProRule annotation9

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processNecrosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		Q8NB16

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-3295583, TRP channels
R-HSA-5213460, RIPK1-mediated regulated necrosis
R-HSA-5675482, Regulation of necroptotic cell death
R-HSA-9686347, Microbial modulation of RIPK1-mediated regulated necrosis

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q8NB16

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q8NB16

Protein family/group databases

Transport Classification Database

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

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Mixed lineage kinase domain-like proteinCurated
Short name:
hMLKL1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MLKL1 PublicationImported
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 16

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:26617, MLKL

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		615153, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q8NB16

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000168404

<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

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi58L → G: Does not affect formation of homotrimers, while translocation to the plasma membrane on necroptosis induction is impaired; when associated with G-76. 1 Publication1
Mutagenesisi76I → G: Does not affect formation of homotrimers, while translocation to the plasma membrane on necroptosis induction is impaired; when associated with G-58. 1 Publication1
Mutagenesisi86C → S: Abolishes binding to necrosulfonamide inhibitor. 1 Publication1
Mutagenesisi162L → G: Impairs formation of homotrimers and translocation to the plasma membrane on necroptosis induction; when associated with G-165. 1 Publication1
Mutagenesisi165L → G: Impairs formation of homotrimers and translocation to the plasma membrane on necroptosis induction; when associated with G-162. 1 Publication1
Mutagenesisi230K → M: Abolishes ATP-binding. 1 Publication1
Mutagenesisi331K → N: Impairs ATP-binding. 1 Publication1
Mutagenesisi351E → K: Binds ATP with an enhanced affinity. 1 Publication1
Mutagenesisi357 – 358TS → ED: Mimics phosphorylation state; acts as a dominant-negative mutant that impairs necroptosis. 2
Mutagenesisi357T → A: No effect. Abolishes ability to mediate necroptosis; when associated with A-358. 1 Publication1
Mutagenesisi358S → A: No effect. Abolishes ability to mediate necroptosis; when associated with A-357. 1 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		197259

Open Targets

More...OpenTargetsi		ENSG00000168404

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA142671349

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q8NB16, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL1938217

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		2106

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		MLKL

Domain mapping of disease mutations (DMDM)

More...DMDMi		74762545

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002482391 – 471Mixed lineage kinase domain-like proteinAdd BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei125PhosphoserineCombined sources1
Modified residuei357Phosphothreonine; by RIPK31 Publication1
Modified residuei358Phosphoserine; by RIPK32 Publications1
Modified residuei360Phosphoserine; by RIPK3By similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylation by RIPK3 induces a conformational switch that is required for necroptosis (PubMed:22265413). It also induces homotrimerization and localization to the plasma membrane (PubMed:22265413).1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

The CPTAC Assay portal

More...CPTACi		CPTAC-895
CPTAC-896

Encyclopedia of Proteome Dynamics

More...EPDi		Q8NB16

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q8NB16

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q8NB16

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q8NB16

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q8NB16

PeptideAtlas

More...PeptideAtlasi		Q8NB16

PRoteomics IDEntifications database

More...PRIDEi		Q8NB16

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		72718 [Q8NB16-1]
72719 [Q8NB16-2]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		Q8NB16, 4 sites, 1 O-linked glycan (4 sites)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q8NB16

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q8NB16

<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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000168404, Expressed in granulocyte and 201 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q8NB16, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q8NB16, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000168404, Low tissue specificity

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homooligomer (PubMed:29883610). Homotrimer; forms homotrimers on necroptosis induction (PubMed:24316671). Upon TNF-induced necrosis, forms in complex with PGAM5, RIPK1 and RIPK3 (PubMed:22265414). Within this complex, may play a role in the proper targeting of RIPK1-RIPK3 to its downstream effector PGAM5 (PubMed:22265414).

Interacts with RIPK3; the interaction is direct and promotes its phosphorylation and subsequent activation (PubMed:22265413, PubMed:22421439, PubMed:29883609).

6 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		128244, 32 interactors

Database of interacting proteins

More...DIPi		DIP-41782N

Protein interaction database and analysis system

More...IntActi		Q8NB16, 21 interactors

Molecular INTeraction database

More...MINTi		Q8NB16

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000308351

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q8NB16

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q8NB16, protein

<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

1471
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		Q8NB16

Biological Magnetic Resonance Data Bank

More...BMRBi		Q8NB16

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q8NB16

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini194 – 469Protein kinasePROSITE-ProRule annotationAdd BLAST276

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 149N-terminal bundle and brace (NBB); mediates INSP6 binding1 PublicationAdd BLAST149

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and domains' section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili55 – 84Sequence analysisAdd BLAST30
Coiled coili139 – 180Sequence analysisAdd BLAST42

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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

<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

Belongs to the protein kinase superfamily.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0192, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00390000016453

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_044216_0_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q8NB16

Identification of Orthologs from Complete Genome Data

More...OMAi		ESKVDWM

Database of Orthologous Groups

More...OrthoDBi		1388260at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q8NB16

TreeFam database of animal gene trees

More...TreeFami		TF328453

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		1.20.930.20, 1 hit

Integrated resource of protein families, domains and functional sites

More...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, PK_Tyr_Ser-Thr, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50011, PROTEIN_KINASE_DOM, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

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

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

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i005E7F7AB6D20649
GO
Isoform 21 Publication (identifier: Q8NB16-2) [UniParc]FASTAAdd to basket

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

Show »
Length:263
Mass (Da):30,279
Checksum:i183FD0023D8A1EC3
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L2T9I3L2T9_HUMAN
Mixed lineage kinase domain-like pr...
MLKL
211Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L4Z5I3L4Z5_HUMAN
Mixed lineage kinase domain-like pr...
MLKL
62Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L4A6I3L4A6_HUMAN
Mixed lineage kinase domain-like pr...
MLKL
175Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
I3L2U3I3L2U3_HUMAN
Mixed lineage kinase domain-like pr...
MLKL
102Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_04135052S → T1 PublicationCorresponds to variant dbSNP:rs34251827Ensembl.1
Natural variantiVAR_041351100D → E1 PublicationCorresponds to variant dbSNP:rs33987771EnsemblClinVar.1
Natural variantiVAR_041352132S → P1 PublicationCorresponds to variant dbSNP:rs35589326EnsemblClinVar.1
Natural variantiVAR_041353146R → Q1 PublicationCorresponds to variant dbSNP:rs34515646EnsemblClinVar.1
Natural variantiVAR_041354169M → L1 PublicationCorresponds to variant dbSNP:rs55929310Ensembl.1
Natural variantiVAR_041355291L → P in a gastric adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1313508921Ensembl.1
Natural variantiVAR_041356364T → M1 PublicationCorresponds to variant dbSNP:rs34389205Ensembl.1
Natural variantiVAR_041357398F → I in a gastric adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041358421R → H1 PublicationCorresponds to variant dbSNP:rs55987292Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_052133179 – 205YLPPK…LSGSP → SLESSSGKSPLEISRFKVKN VKTGSAS in isoform 2. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_052134206 – 413Missing in isoform 2. 1 PublicationAdd BLAST208

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000306247.11; ENSP00000303118.7; ENSG00000168404.13 [Q8NB16-2]
ENST00000308807.12; ENSP00000308351.7; ENSG00000168404.13

Database of genes from NCBI RefSeq genomes

More...GeneIDi		197259

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:197259

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000308807.12; ENSP00000308351.7; NM_152649.4; NP_689862.1

UCSC genome browser

More...UCSCi		uc002fdb.3, human [Q8NB16-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<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

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
CCDSiCCDS32487.1 [Q8NB16-1]
CCDS45528.1 [Q8NB16-2]
RefSeqiNP_001135969.1, NM_001142497.2 [Q8NB16-2]
NP_689862.1, NM_152649.3 [Q8NB16-1]
XP_005255891.1, XM_005255834.3 [Q8NB16-1]

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 entryMethodResolution (Å)ChainPositionsPDBsum
2MSVNMR-A1-154[»]
4M67X-ray1.90A179-471[»]
4MWIX-ray1.70A183-471[»]
5KNJX-ray2.88A/B191-471[»]
5KO1X-ray2.16A191-471[»]
6BWKX-ray2.79A190-471[»]
6D74NMR-A1-156[»]
6LK5X-ray2.50A1-471[»]
6LK6X-ray2.41A179-471[»]
6O5ZX-ray2.29A/B190-471[»]
6UX8X-ray2.50A5-154[»]
6ZLENMR-A2-154[»]
6ZPRNMR-A2-154[»]
6ZVOX-ray1.37A/B/C2-150[»]
6ZZ1X-ray1.64A/B2-150[»]
7JW7X-ray2.63A190-471[»]
7JXUX-ray2.44A/B190-471[»]
7MONX-ray2.23A190-471[»]
7NM2NMR-A2-154[»]
7NM4NMR-A2-154[»]
7NM5NMR-A2-154[»]
AlphaFoldDBiQ8NB16
BMRBiQ8NB16
SMRiQ8NB16
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi128244, 32 interactors
DIPiDIP-41782N
IntActiQ8NB16, 21 interactors
MINTiQ8NB16
STRINGi9606.ENSP00000308351

Chemistry databases

BindingDBiQ8NB16
ChEMBLiCHEMBL1938217
GuidetoPHARMACOLOGYi2106

Protein family/group databases

TCDBi1.A.105.1.1, the mixed lineage kinase domain-like (mlkl) family

PTM databases

GlyGeniQ8NB16, 4 sites, 1 O-linked glycan (4 sites)
iPTMnetiQ8NB16
PhosphoSitePlusiQ8NB16

Genetic variation databases

BioMutaiMLKL
DMDMi74762545

Proteomic databases

CPTACiCPTAC-895
CPTAC-896
EPDiQ8NB16
jPOSTiQ8NB16
MassIVEiQ8NB16
MaxQBiQ8NB16
PaxDbiQ8NB16
PeptideAtlasiQ8NB16
PRIDEiQ8NB16
ProteomicsDBi72718 [Q8NB16-1]
72719 [Q8NB16-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		2097, 353 antibodies from 38 providers

The DNASU plasmid repository

More...DNASUi		197259

Genome annotation databases

EnsembliENST00000306247.11; ENSP00000303118.7; ENSG00000168404.13 [Q8NB16-2]
ENST00000308807.12; ENSP00000308351.7; ENSG00000168404.13
GeneIDi197259
KEGGihsa:197259
MANE-SelectiENST00000308807.12; ENSP00000308351.7; NM_152649.4; NP_689862.1
UCSCiuc002fdb.3, human [Q8NB16-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		197259
DisGeNETi197259

GeneCards: human genes, protein and diseases

More...GeneCardsi		MLKL
HGNCiHGNC:26617, MLKL
HPAiENSG00000168404, Low tissue specificity
MIMi615153, gene
neXtProtiNX_Q8NB16
OpenTargetsiENSG00000168404
PharmGKBiPA142671349
VEuPathDBiHostDB:ENSG00000168404

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0192, Eukaryota
GeneTreeiENSGT00390000016453
HOGENOMiCLU_044216_0_0_1
InParanoidiQ8NB16
OMAiESKVDWM
OrthoDBi1388260at2759
PhylomeDBiQ8NB16
TreeFamiTF328453

Enzyme and pathway databases

PathwayCommonsiQ8NB16
ReactomeiR-HSA-3295583, TRP channels
R-HSA-5213460, RIPK1-mediated regulated necrosis
R-HSA-5675482, Regulation of necroptotic cell death
R-HSA-9686347, Microbial modulation of RIPK1-mediated regulated necrosis
SignaLinkiQ8NB16
SIGNORiQ8NB16

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		197259, 15 hits in 1114 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		MLKL, human

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		197259
PharosiQ8NB16, Tchem

Protein Ontology

More...PROi		PR:Q8NB16
RNActiQ8NB16, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000168404, Expressed in granulocyte and 201 other tissues
ExpressionAtlasiQ8NB16, baseline and differential
GenevisibleiQ8NB16, HS

Family and domain databases

Gene3Di1.20.930.20, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF07714, PK_Tyr_Ser-Thr, 1 hit
SUPFAMiSSF56112, SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011, PROTEIN_KINASE_DOM, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<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 subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiMLKL_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q8NB16
Secondary accession number(s): A6NCE4, Q8N6V0
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: October 1, 2002
Last modified: May 25, 2022
This is version 167 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<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

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. Human entries with genetic variants
    List of human entries with genetic variants
  4. Human variants curated from literature reports
    Index of human variants curated from literature reports
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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