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Aliases for MLKL Gene

Aliases for MLKL Gene

  • Mixed Lineage Kinase Domain-Like 2 3
  • HMLKL 3 4
  • Mixed Lineage Kinase Domain-Like Protein 3

External Ids for MLKL Gene

Previous GeneCards Identifiers for MLKL Gene

  • GC16M073264
  • GC16M060455

Summaries for MLKL Gene

GeneCards Summary for MLKL Gene

MLKL (Mixed Lineage Kinase Domain-Like) is a Protein Coding gene. Among its related pathways are TNF signaling pathway and Wnt Signaling Pathway (WikiPathways). GO annotations related to this gene include protein kinase activity.

UniProtKB/Swiss-Prot for MLKL Gene

  • 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.

No data available for Entrez Gene Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MLKL Gene

Genomics for MLKL Gene

Regulatory Elements for MLKL Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for MLKL Gene

Start:
74,671,855 bp from pter
End:
74,700,960 bp from pter
Size:
29,106 bases
Orientation:
Minus strand

Genomic View for MLKL Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MLKL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MLKL Gene

Proteins for MLKL Gene

  • Protein details for MLKL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8NB16-MLKL_HUMAN
    Recommended name:
    Mixed lineage kinase domain-like protein
    Protein Accession:
    Q8NB16
    Secondary Accessions:
    • A6NCE4
    • Q8N6V0

    Protein attributes for MLKL Gene

    Size:
    471 amino acids
    Molecular mass:
    54479 Da
    Quaternary structure:
    • 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.
    Miscellaneous:
    • Interaction with RIPK3 is species specific: human MLKL only interacts with human RIPK3 and not mouse RIPK3.

    Three dimensional structures from OCA and Proteopedia for MLKL Gene

    Alternative splice isoforms for MLKL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MLKL Gene

Proteomics data for MLKL Gene at MOPED

Post-translational modifications for MLKL Gene

  • Phosphorylation by RIPK3 induces a conformational switch that is required for necroptosis. It also induces homotrimerization and localization to the plasma membrane.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MLKL Gene

No data available for DME Specific Peptides for MLKL Gene

Domains for MLKL Gene

Gene Families for MLKL Gene

Protein Domains for MLKL Gene

Suggested Antigen Peptide Sequences for MLKL Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8NB16

UniProtKB/Swiss-Prot:

MLKL_HUMAN :
  • Q8NB16
Domain:
  • 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).
  • The coiled coil region 2 is responsible for homotrimerization.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily.
genes like me logo Genes that share domains with MLKL: view

Function for MLKL Gene

Molecular function for MLKL Gene

UniProtKB/Swiss-Prot EnzymeRegulation: Inhibited by necrosulfonamide, a specific inhibitor of necroptosis that targets Cys-86.
UniProtKB/Swiss-Prot Function: 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.

Gene Ontology (GO) - Molecular Function for MLKL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 NOT protein kinase activity ISS --
GO:0004674 protein serine/threonine kinase activity TAS --
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding IPI 22265413
GO:0005524 ATP binding IDA 24219132
genes like me logo Genes that share ontologies with MLKL: view
genes like me logo Genes that share phenotypes with MLKL: view

Animal Models for MLKL Gene

MGI Knock Outs for MLKL:

Animal Model Products

CRISPR Products

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for MLKL Gene

Localization for MLKL Gene

Subcellular locations from UniProtKB/Swiss-Prot for MLKL Gene

Cytoplasm. Cell membrane. Note=Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MLKL Gene COMPARTMENTS Subcellular localization image for MLKL gene
Compartment Confidence
cytosol 3
nucleus 2
endoplasmic reticulum 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for MLKL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 24316671
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IDA 24316671
genes like me logo Genes that share ontologies with MLKL: view

Pathways for MLKL Gene

genes like me logo Genes that share pathways with MLKL: view

Pathways by source for MLKL Gene

1 BioSystems pathway for MLKL Gene
1 KEGG pathway for MLKL Gene

Gene Ontology (GO) - Biological Process for MLKL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA --
GO:0012501 programmed cell death TAS --
GO:0070207 protein homotrimerization IDA 24316671
GO:0070266 necroptotic process TAS --
GO:0097300 programmed necrotic cell death TAS --
genes like me logo Genes that share ontologies with MLKL: view

Compounds for MLKL Gene

(2) HMDB Compounds for MLKL Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
genes like me logo Genes that share compounds with MLKL: view

Transcripts for MLKL Gene

Unigene Clusters for MLKL Gene

Mixed lineage kinase domain-like:
Representative Sequences:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MLKL

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for MLKL Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11
SP1: - - -
SP2: -
SP3: - - - - - - - -
SP4:

Relevant External Links for MLKL Gene

GeneLoc Exon Structure for
MLKL
ECgene alternative splicing isoforms for
MLKL

Expression for MLKL Gene

mRNA expression in normal human tissues for MLKL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MLKL Gene

This gene is overexpressed in Whole Blood (10.1).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MLKL Gene

SOURCE GeneReport for Unigene cluster for MLKL Gene Hs.119878

genes like me logo Genes that share expressions with MLKL: view

In Situ Assay Products

No data available for mRNA Expression by UniProt/SwissProt for MLKL Gene

Orthologs for MLKL Gene

This gene was present in the common ancestor of chordates.

Orthologs for MLKL Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MLKL 35
  • 98.8 (n)
  • 97.66 (a)
MLKL 36
  • 98 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MLKL 35
  • 77.47 (n)
  • 64.59 (a)
MLKL 36
  • 63 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Mlkl 35
  • 75.92 (n)
  • 63.66 (a)
Mlkl 16
Mlkl 36
  • 62 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MLKL 36
  • 48 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Mlkl 35
  • 75.81 (n)
  • 64.16 (a)
chicken
(Gallus gallus)
Aves MLKL 35
  • 54.2 (n)
  • 41.45 (a)
MLKL 36
  • 40 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MLKL 36
  • 41 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia mlkl 35
  • 48.97 (n)
  • 37.67 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 24 (a)
OneToOne
Species with no ortholog for MLKL:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for MLKL Gene

ENSEMBL:
Gene Tree for MLKL (if available)
TreeFam:
Gene Tree for MLKL (if available)

Paralogs for MLKL Gene

Selected SIMAP similar genes for MLKL Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with MLKL: view

No data available for Paralogs for MLKL Gene

Variants for MLKL Gene

Sequence variations from dbSNP and Humsavar for MLKL Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type MAF
rs8998 -- 74,672,063(+) CATGT(C/T)CATGG utr-variant-3-prime, nc-transcript-variant
rs877375 -- 74,700,969(+) TCACT(C/G)GGTAA upstream-variant-2KB
rs2002756 -- 74,701,365(+) GCTCA(A/T)GCCTG upstream-variant-2KB
rs2057803 -- 74,701,544(+) aatcg(C/T)ttgaa upstream-variant-2KB
rs2057804 -- 74,701,581(+) CCTTG(C/G)TATTG upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for MLKL Gene

Variant ID Type Subtype PubMed ID
esv275138 CNV Gain+Loss 21479260
nsv906906 CNV Gain 21882294
nsv906907 CNV Loss 21882294

Relevant External Links for MLKL Gene

HapMap Linkage Disequilibrium report
MLKL

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MLKL Gene

Disorders for MLKL Gene

Relevant External Links for MLKL

Genetic Association Database (GAD)
MLKL
Human Genome Epidemiology (HuGE) Navigator
MLKL
genes like me logo Genes that share disorders with MLKL: view

No data available for UniProtKB/Swiss-Prot for MLKL Gene

Publications for MLKL Gene

  1. The protein kinase complement of the human genome. (PMID: 12471243) Manning G. … Sudarsanam S. (Science 2002) 3 4
  2. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PMID: 12477932) Strausberg R.L. … Marra M.A. (Proc. Natl. Acad. Sci. U.S.A. 2002) 2 3
  3. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T. … Sugano S. (Nat. Genet. 2004) 3 4
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard D.S. … Malek J. (Genome Res. 2004) 3 4
  5. Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects. (PMID: 19844255) Dastani Z. … Genest J. (Eur. J. Hum. Genet. 2010) 3 48

Products for MLKL Gene

Sources for MLKL Gene

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