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Q8NB16

- MLKL_HUMAN

UniProt

Q8NB16 - MLKL_HUMAN

Protein

Mixed lineage kinase domain-like protein

Gene

MLKL

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 1 (01 Oct 2002)
      Previous versions | rss
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    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.4 Publications

    Enzyme regulationi

    Inhibited by necrosulfonamide, a specific inhibitor of necroptosis that targets Cys-86.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei86 – 861Target of necrosulfonamide inhibitor
    Binding sitei230 – 2301ATPCurated

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi209 – 2179ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB
    2. protein binding Source: IntAct
    3. protein complex binding Source: UniProtKB
    4. transferase activity, transferring phosphorus-containing groups Source: InterPro

    GO - Biological processi

    1. necroptotic process Source: UniProtKB
    2. protein homotrimerization Source: UniProtKB
    3. protein phosphorylation Source: InterPro

    Keywords - Biological processi

    Necrosis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mixed lineage kinase domain-like protein
    Short name:
    hMLKL
    Gene namesi
    Name:MLKLImported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:26617. MLKL.

    Subcellular locationi

    Cytoplasm 1 Publication. Cell membrane 1 Publication
    Note: Localizes to the cytoplasm and translocates to the plasma membrane on necroptosis induction.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi58 – 581L → 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
    Mutagenesisi76 – 761I → 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
    Mutagenesisi86 – 861C → S: Abolishes binding to necrosulfonamide inhibitor. 1 Publication
    Mutagenesisi162 – 1621L → G: Impairs formation of homotrimers and translocation to the plasma membrane on necroptosis induction; when associated with G-165. 1 Publication
    Mutagenesisi165 – 1651L → G: Impairs formation of homotrimers and translocation to the plasma membrane on necroptosis induction; when associated with G-162. 1 Publication
    Mutagenesisi230 – 2301K → M: Abolishes ATP-binding. 1 Publication
    Mutagenesisi331 – 3311K → N: Impairs ATP-binding. 1 Publication
    Mutagenesisi351 – 3511E → K: Binds ATP with an enhanced affinity. 1 Publication
    Mutagenesisi357 – 3582TS → ED: Mimics phosphorylation state; acts as a dominant-negative mutant that impairs necroptosis. 1 Publication
    Mutagenesisi357 – 3571T → A: No effect. Abolishes ability to mediate necroptosis; when associated with A-358. 1 Publication
    Mutagenesisi358 – 3581S → A: No effect. Abolishes ability to mediate necroptosis; when associated with A-357. 1 Publication

    Organism-specific databases

    PharmGKBiPA142671349.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 471471Mixed lineage kinase domain-like proteinPRO_0000248239Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei125 – 1251Phosphoserine2 Publications
    Modified residuei357 – 3571Phosphothreonine; by RIPK31 Publication
    Modified residuei358 – 3581Phosphoserine; by RIPK31 Publication
    Modified residuei360 – 3601Phosphoserine; by RIPK3By similarity

    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.3 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ8NB16.
    PaxDbiQ8NB16.
    PRIDEiQ8NB16.

    PTM databases

    PhosphoSiteiQ8NB16.

    Expressioni

    Gene expression databases

    ArrayExpressiQ8NB16.
    BgeeiQ8NB16.
    CleanExiHS_MLKL.
    GenevestigatoriQ8NB16.

    Organism-specific databases

    HPAiHPA010535.
    HPA046756.

    Interactioni

    Subunit structurei

    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 PGAM5.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RIPK3Q9Y57210EBI-1055040,EBI-298250

    Protein-protein interaction databases

    BioGridi128244. 7 interactions.
    DIPiDIP-41782N.
    IntActiQ8NB16. 7 interactions.
    MINTiMINT-1033261.
    STRINGi9606.ENSP00000308351.

    Structurei

    Secondary structure

    1
    471
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi198 – 2014
    Beta strandi207 – 2115
    Beta strandi213 – 22210
    Beta strandi225 – 2328
    Helixi240 – 25617
    Beta strandi265 – 2717
    Beta strandi274 – 2763
    Beta strandi278 – 2847
    Helixi291 – 2977
    Helixi303 – 32220
    Beta strandi323 – 3253
    Helixi334 – 3363
    Beta strandi337 – 3393
    Beta strandi345 – 3473
    Helixi373 – 3764
    Helixi379 – 3835
    Helixi391 – 40717
    Turni411 – 4144
    Helixi417 – 4259
    Helixi439 – 44810
    Helixi453 – 4553
    Helixi459 – 4679

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4M67X-ray1.90A179-471[»]
    4MWIX-ray1.70A183-471[»]
    ProteinModelPortaliQ8NB16.
    SMRiQ8NB16. Positions 2-470.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini194 – 469276Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili55 – 8430Sequence AnalysisAdd
    BLAST
    Coiled coili139 – 18042Sequence AnalysisAdd
    BLAST

    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
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000113601.
    HOVERGENiHBG056156.
    InParanoidiQ8NB16.
    KOiK08849.
    OMAiICIDETV.
    OrthoDBiEOG7P5T0V.
    PhylomeDBiQ8NB16.
    TreeFamiTF328453.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

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

    MENLKHIITL GQVIHKRCEE MKYCKKQCRR LGHRVLGLIK PLEMLQDQGK    50
    RSVPSEKLTT AMNRFKAALE EANGEIEKFS NRSNICRFLT ASQDKILFKD 100
    VNRKLSDVWK ELSLLLQVEQ RMPVSPISQG ASWAQEDQQD ADEDRRAFQM 150
    LRRDNEKIEA SLRRLEINMK EIKETLRQYL PPKCMQEIPQ EQIKEIKKEQ 200
    LSGSPWILLR ENEVSTLYKG EYHRAPVAIK VFKKLQAGSI AIVRQTFNKE 250
    IKTMKKFESP NILRIFGICI DETVTPPQFS IVMEYCELGT LRELLDREKD 300
    LTLGKRMVLV LGAARGLYRL HHSEAPELHG KIRSSNFLVT QGYQVKLAGF 350
    ELRKTQTSMS LGTTREKTDR VKSTAYLSPQ ELEDVFYQYD VKSEIYSFGI 400
    VLWEIATGDI PFQGCNSEKI RKLVAVKRQQ EPLGEDCPSE LREIIDECRA 450
    HDPSVRPSVD EILKKLSTFS K 471
    Length:471
    Mass (Da):54,479
    Last modified:October 1, 2002 - v1
    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.

    Note: No experimental confirmation available.Curated

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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti52 – 521S → T.1 Publication
    Corresponds to variant rs34251827 [ dbSNP | Ensembl ].
    VAR_041350
    Natural varianti100 – 1001D → E.1 Publication
    Corresponds to variant rs33987771 [ dbSNP | Ensembl ].
    VAR_041351
    Natural varianti132 – 1321S → P.1 Publication
    Corresponds to variant rs35589326 [ dbSNP | Ensembl ].
    VAR_041352
    Natural varianti146 – 1461R → Q.1 Publication
    Corresponds to variant rs34515646 [ dbSNP | Ensembl ].
    VAR_041353
    Natural varianti169 – 1691M → L.1 Publication
    Corresponds to variant rs55929310 [ dbSNP | Ensembl ].
    VAR_041354
    Natural varianti291 – 2911L → P in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041355
    Natural varianti364 – 3641T → M.1 Publication
    Corresponds to variant rs34389205 [ dbSNP | Ensembl ].
    VAR_041356
    Natural varianti398 – 3981F → I in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041357
    Natural varianti421 – 4211R → H.1 Publication
    Corresponds to variant rs55987292 [ dbSNP | Ensembl ].
    VAR_041358

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei179 – 20527YLPPK…LSGSP → SLESSSGKSPLEISRFKVKN VKTGSAS in isoform 2. 1 PublicationVSP_052133Add
    BLAST
    Alternative sequencei206 – 413208Missing in isoform 2. 1 PublicationVSP_052134Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_001142497.1. [Q8NB16-2]
    NP_689862.1. NM_152649.2. [Q8NB16-1]
    XP_005255891.1. XM_005255834.1. [Q8NB16-1]
    UniGeneiHs.119878.

    Genome annotation databases

    EnsembliENST00000306247; ENSP00000303118; ENSG00000168404. [Q8NB16-2]
    ENST00000308807; ENSP00000308351; ENSG00000168404. [Q8NB16-1]
    GeneIDi197259.
    KEGGihsa:197259.
    UCSCiuc002fdb.2. human. [Q8NB16-1]
    uc002fdc.2. human. [Q8NB16-2]

    Polymorphism databases

    DMDMi74762545.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_001142497.1. [Q8NB16-2 ]
    NP_689862.1. NM_152649.2. [Q8NB16-1 ]
    XP_005255891.1. XM_005255834.1. [Q8NB16-1 ]
    UniGenei Hs.119878.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4M67 X-ray 1.90 A 179-471 [» ]
    4MWI X-ray 1.70 A 183-471 [» ]
    ProteinModelPortali Q8NB16.
    SMRi Q8NB16. Positions 2-470.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 128244. 7 interactions.
    DIPi DIP-41782N.
    IntActi Q8NB16. 7 interactions.
    MINTi MINT-1033261.
    STRINGi 9606.ENSP00000308351.

    Chemistry

    ChEMBLi CHEMBL1938217.

    PTM databases

    PhosphoSitei Q8NB16.

    Polymorphism databases

    DMDMi 74762545.

    Proteomic databases

    MaxQBi Q8NB16.
    PaxDbi Q8NB16.
    PRIDEi Q8NB16.

    Protocols and materials databases

    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.2. human. [Q8NB16-1 ]
    uc002fdc.2. human. [Q8NB16-2 ]

    Organism-specific databases

    CTDi 197259.
    GeneCardsi GC16M074705.
    HGNCi HGNC:26617. MLKL.
    HPAi HPA010535.
    HPA046756.
    MIMi 615153. gene.
    neXtProti NX_Q8NB16.
    PharmGKBi PA142671349.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000113601.
    HOVERGENi HBG056156.
    InParanoidi Q8NB16.
    KOi K08849.
    OMAi ICIDETV.
    OrthoDBi EOG7P5T0V.
    PhylomeDBi Q8NB16.
    TreeFami TF328453.

    Miscellaneous databases

    ChiTaRSi MLKL. human.
    GenomeRNAii 197259.
    NextBioi 89630.
    PROi Q8NB16.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8NB16.
    Bgeei Q8NB16.
    CleanExi HS_MLKL.
    Genevestigatori Q8NB16.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    [Graphical view ]
    Pfami PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NOMENCLATURE.
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: ChondrocyteImported.
    3. "The sequence and analysis of duplication-rich human chromosome 16."
      Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
      , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
      Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: LeukocyteImported.
    5. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    7. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    8. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    10. "Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase."
      Sun L., Wang H., Wang Z., He S., Chen S., Liao D., Wang L., Yan J., Liu W., Lei X., Wang X.
      Cell 148:213-227(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RIPK3, ENZYME REGULATION, PHOSPHORYLATION AT THR-357 AND SER-358, MUTAGENESIS OF CYS-86; THR-357 AND SER-358.
    11. "The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways."
      Wang Z., Jiang H., Chen S., Du F., Wang X.
      Cell 148:228-243(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN COMPLEX WITH PGAM5; RIPK1 AND RIPK3.
    12. "Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis."
      Zhao J., Jitkaew S., Cai Z., Choksi S., Li Q., Luo J., Liu Z.G.
      Proc. Natl. Acad. Sci. U.S.A. 109:5322-5327(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RIPK3.
    13. "Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis."
      Cai Z., Jitkaew S., Zhao J., Chiang H.C., Choksi S., Liu J., Ward Y., Wu L.G., Liu Z.G.
      Nat. Cell Biol. 16:55-65(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, MUTAGENESIS OF LEU-58; ILE-76; LEU-162 AND LEU-165.
    14. "Insights into the evolution of divergent nucleotide-binding mechanisms among pseudokinases revealed by crystal structures of human and mouse MLKL."
      Murphy J.M., Lucet I.S., Hildebrand J.M., Tanzer M.C., Young S.N., Sharma P., Lessene G., Alexander W.S., Babon J.J., Silke J., Czabotar P.E.
      Biochem. J. 457:369-377(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 189-471, ATP-BINDING, MUTAGENESIS OF LYS-230; LYS-331 AND GLU-351.
    15. "Structural insights into RIP3-mediated necroptotic signaling."
      Xie T., Peng W., Yan C., Wu J., Gong X., Shi Y.
      Cell Rep. 5:70-78(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 179-471.
    16. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-52; GLU-100; PRO-132; GLN-146; LEU-169; PRO-291; MET-364; ILE-398 AND HIS-421.

    Entry informationi

    Entry nameiMLKL_HUMAN
    AccessioniPrimary (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: October 1, 2014
    This is version 106 of the entry and version 1 of the sequence. [Complete history]
    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.

    Miscellaneousi

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3