LOCUS       NM_152649               2477 bp    mRNA    linear   PRI 24-SEP-2024
DEFINITION  Homo sapiens mixed lineage kinase domain like pseudokinase (MLKL),
            transcript variant 1, mRNA.
ACCESSION   NM_152649 XM_936963
VERSION     NM_152649.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2477)
  AUTHORS   Davies,K.A., Czabotar,P.E. and Murphy,J.M.
  TITLE     Death at a funeral: Activation of the dead enzyme, MLKL, to kill
            cells by necroptosis
  JOURNAL   Curr Opin Struct Biol 88, 102891 (2024)
   PUBMED   39059047
  REMARK    GeneRIF: Death at a funeral: Activation of the dead enzyme, MLKL,
            to kill cells by necroptosis.
            Review article
REFERENCE   2  (bases 1 to 2477)
  AUTHORS   Yu,X., Feng,M., Guo,J., Wang,H., Yu,J., Zhang,A., Wu,J., Han,Y.,
            Sun,Z., Liao,Y. and Zhao,Q.
  TITLE     MLKL promotes hepatocarcinogenesis through inhibition of
            AMPK-mediated autophagy
  JOURNAL   Cell Death Differ 31 (8), 1085-1098 (2024)
   PUBMED   38783090
  REMARK    GeneRIF: MLKL promotes hepatocarcinogenesis through inhibition of
            AMPK-mediated autophagy.
REFERENCE   3  (bases 1 to 2477)
  AUTHORS   El Feky,S.E., Fakhry,K.A., Hussain,A.M., Ibrahim,F.A.R. and
            Morsi,M.I.
  TITLE     MLKL regulates radiation-induced death in breast cancer cells: an
            interplay between apoptotic and necroptotic signals
  JOURNAL   Med Oncol 41 (7), 172 (2024)
   PUBMED   38862702
  REMARK    GeneRIF: MLKL regulates radiation-induced death in breast cancer
            cells: an interplay between apoptotic and necroptotic signals.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2477)
  AUTHORS   Liu,S., Perez,P., Sun,X., Chen,K., Fatirkhorani,R., Mammadova,J.
            and Wang,Z.
  TITLE     MLKL polymerization-induced lysosomal membrane permeabilization
            promotes necroptosis
  JOURNAL   Cell Death Differ 31 (1), 40-52 (2024)
   PUBMED   37996483
  REMARK    GeneRIF: MLKL polymerization-induced lysosomal membrane
            permeabilization promotes necroptosis.
REFERENCE   5  (bases 1 to 2477)
  AUTHORS   Geng,L., Gao,W., Saiyin,H., Li,Y., Zeng,Y., Zhang,Z., Li,X.,
            Liu,Z., Gao,Q., An,P., Jiang,N., Yu,X., Chen,X., Li,S., Chen,L.,
            Lu,B., Li,A., Chen,G., Shen,Y., Zhang,H., Tian,M., Zhang,Z. and
            Li,J.
  TITLE     MLKL deficiency alleviates neuroinflammation and motor deficits in
            the alpha-synuclein transgenic mouse model of Parkinson's disease
  JOURNAL   Mol Neurodegener 18 (1), 94 (2023)
   PUBMED   38041169
  REMARK    GeneRIF: MLKL deficiency alleviates neuroinflammation and motor
            deficits in the alpha-synuclein transgenic mouse model of
            Parkinson's disease.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 2477)
  AUTHORS   Zhao,J., Jitkaew,S., Cai,Z., Choksi,S., Li,Q., Luo,J. and Liu,Z.G.
  TITLE     Mixed lineage kinase domain-like is a key receptor interacting
            protein 3 downstream component of TNF-induced necrosis
  JOURNAL   Proc Natl Acad Sci U S A 109 (14), 5322-5327 (2012)
   PUBMED   22421439
  REMARK    GeneRIF: study suggests that MLKL is a key RIP3 downstream
            component of TNF-induced necrotic cell death
REFERENCE   7  (bases 1 to 2477)
  AUTHORS   Wang,Z., Jiang,H., Chen,S., Du,F. and Wang,X.
  TITLE     The mitochondrial phosphatase PGAM5 functions at the convergence
            point of multiple necrotic death pathways
  JOURNAL   Cell 148 (1-2), 228-243 (2012)
   PUBMED   22265414
REFERENCE   8  (bases 1 to 2477)
  AUTHORS   Sun,L., Wang,H., Wang,Z., He,S., Chen,S., Liao,D., Wang,L., Yan,J.,
            Liu,W., Lei,X. and Wang,X.
  TITLE     Mixed lineage kinase domain-like protein mediates necrosis
            signaling downstream of RIP3 kinase
  JOURNAL   Cell 148 (1-2), 213-227 (2012)
   PUBMED   22265413
  REMARK    GeneRIF: Findings implicate MLKL as a key mediator of necrosis
            signaling downstream of the kinase RIP3.
REFERENCE   9  (bases 1 to 2477)
  AUTHORS   Dastani,Z., Pajukanta,P., Marcil,M., Rudzicz,N., Ruel,I.,
            Bailey,S.D., Lee,J.C., Lemire,M., Faith,J., Platko,J., Rioux,J.,
            Hudson,T.J., Gaudet,D., Engert,J.C. and Genest,J.
  TITLE     Fine mapping and association studies of a high-density lipoprotein
            cholesterol linkage region on chromosome 16 in French-Canadian
            subjects
  JOURNAL   Eur J Hum Genet 18 (3), 342-347 (2010)
   PUBMED   19844255
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
REFERENCE   10 (bases 1 to 2477)
  AUTHORS   Manning,G., Whyte,D.B., Martinez,R., Hunter,T. and Sudarsanam,S.
  TITLE     The protein kinase complement of the human genome
  JOURNAL   Science 298 (5600), 1912-1934 (2002)
   PUBMED   12471243
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK091708.1, BC028141.1 and
            BQ575071.1.
            
            On Nov 22, 2018 this sequence version replaced NM_152649.3.
            
            Summary: This gene belongs to the protein kinase superfamily. The
            encoded protein contains a protein kinase-like domain; however, is
            thought to be inactive because it lacks several residues required
            for activity. This protein plays a critical role in tumor necrosis
            factor (TNF)-induced necroptosis, a programmed cell death process,
            via interaction with receptor-interacting protein 3 (RIP3), which
            is a key signaling molecule in necroptosis pathway. Inhibitor
            studies and knockdown of this gene inhibited TNF-induced necrosis.
            High levels of this protein and RIP3 are associated with
            inflammatory bowel disease in children. Alternatively spliced
            transcript variants have been described for this gene. [provided by
            RefSeq, Sep 2015].
            
            Transcript Variant: This variant (1, also known as MLKLshRNA-A)
            represents the longer transcript and encodes the longer isoform
            (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK091708.1, SRR18074968.3860329.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000308807.12/ ENSP00000308351.7
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1851              AK091708.1         30-1880
            1852-1931           BC028141.1         1156-1235
            1932-2477           BQ575071.1         17-562              c
FEATURES             Location/Qualifiers
     source          1..2477
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q23.1"
     gene            1..2477
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /note="mixed lineage kinase domain like pseudokinase"
                     /db_xref="GeneID:197259"
                     /db_xref="HGNC:HGNC:26617"
                     /db_xref="MIM:615153"
     exon            1..410
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            411..872
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     CDS             413..1828
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /note="isoform 1 is encoded by transcript variant 1; mixed
                     lineage kinase domain-like protein"
                     /codon_start=1
                     /product="mixed lineage kinase domain-like protein isoform
                     1"
                     /protein_id="NP_689862.1"
                     /db_xref="CCDS:CCDS32487.1"
                     /db_xref="GeneID:197259"
                     /db_xref="HGNC:HGNC:26617"
                     /db_xref="MIM:615153"
                     /translation="MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEM
                     LQDQGKRSVPSEKLTTAMNRFKAALEEANGEIEKFSNRSNICRFLTASQDKILFKDVN
                     RKLSDVWKELSLLLQVEQRMPVSPISQGASWAQEDQQDADEDRRAFQMLRRDNEKIEA
                     SLRRLEINMKEIKETLRQYLPPKCMQEIPQEQIKEIKKEQLSGSPWILLRENEVSTLY
                     KGEYHRAPVAIKVFKKLQAGSIAIVRQTFNKEIKTMKKFESPNILRIFGICIDETVTP
                     PQFSIVMEYCELGTLRELLDREKDLTLGKRMVLVLGAARGLYRLHHSEAPELHGKIRS
                     SNFLVTQGYQVKLAGFELRKTQTSMSLGTTREKTDRVKSTAYLSPQELEDVFYQYDVK
                     SEIYSFGIVLWEIATGDIPFQGCNSEKIRKLVAVKRQQEPLGEDCPSELREIIDECRA
                     HDPSVRPSVDEILKKLSTFSK"
     exon            873..947
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            948..1134
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            1135..1232
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            1233..1368
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            1369..1450
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            1451..1602
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            1603..1652
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            1653..1793
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     exon            1794..2477
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2451..2456
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /note="hexamer: AATAAA"
     polyA_site      2477
                     /gene="MLKL"
                     /gene_synonym="hMLKL"
                     /note="major polyA site"
ORIGIN      
        1 gtgagcctgg tggttggcag ctggagccac gtcggagggg gaagtgtcgc agcattctct
       61 gcaggcatca cagacctgag gcagtggcct ccggagggca ctggacagaa acagccatcc
      121 aagtggctga gtggagggac cctgctcaag tgcagctgca gtggccgggg tttccctcag
      181 gtagggatcg gggcgccttg tcgccgccag ccacgtgtgg cgtccggtac agtcagcaga
      241 gtgcagggtg cgggcaccag gaaagggggc gcaggggaac tcccgcgggc ctcgcgtttg
      301 caaacttctc gcctgggcag gaggcggtcg tgggaaagaa ggtggaagag cgagcttttt
      361 ggaactgtgc acgggacaga ttggacgcac acccctcggg aggcgcgaag gcatggaaaa
      421 tttgaagcat attatcaccc ttggccaggt catccacaaa cggtgtgaag agatgaaata
      481 ctgcaagaaa cagtgccggc gcctgggcca ccgcgtcctc ggcctgatca agcctctgga
      541 gatgctccag gaccaaggaa agaggagcgt gccctctgag aagttaacca cagccatgaa
      601 ccgcttcaag gctgccctgg aggaggctaa tggggagata gaaaagttca gcaatagatc
      661 caatatctgc aggtttctaa cagcaagcca ggacaaaata ctcttcaagg acgtgaacag
      721 gaagctgagt gatgtctgga aggagctctc gctgttactt caggttgagc aacgcatgcc
      781 tgtttcaccc ataagccaag gagcgtcctg ggcacaggaa gatcagcagg atgcagacga
      841 agacaggcga gctttccaga tgctaagaag agataatgaa aaaatagaag cttcactgag
      901 acgattagaa atcaacatga aagaaatcaa ggaaactttg aggcagtatt taccaccaaa
      961 atgcatgcag gagatcccgc aagagcaaat caaggagatc aagaaggagc agctttcagg
     1021 atccccgtgg attctgctaa gggaaaatga agtcagcaca ctttataaag gagaatacca
     1081 cagagctcca gtggccataa aagtattcaa aaaactccag gctggcagca ttgcaatagt
     1141 gaggcagact ttcaataagg agatcaaaac catgaagaaa ttcgaatctc ccaacatcct
     1201 gcgtatattt gggatttgca ttgatgaaac agtgactccg cctcaattct ccattgtcat
     1261 ggagtactgt gaactcggga ccctgaggga gctgttggat agggaaaaag acctcacact
     1321 tggcaagcgc atggtcctag tcctgggggc agcccgaggc ctataccggc tacaccattc
     1381 agaagcacct gaactccacg gaaaaatcag aagctcaaac ttcctggtaa ctcaaggcta
     1441 ccaagtgaag cttgcaggat ttgagttgag gaaaacacag acttccatga gtttgggaac
     1501 tacgagagaa aagacagaca gagtcaaatc tacagcatat ctctcacctc aggaactgga
     1561 agatgtattt tatcaatatg atgtaaagtc tgaaatatac agctttggaa tcgtcctctg
     1621 ggaaatcgcc actggagata tcccgtttca aggctgtaat tctgagaaga tccgcaagct
     1681 ggtggctgtg aagcggcagc aggagccact gggtgaagac tgcccttcag agctgcggga
     1741 gatcattgat gagtgccggg cccatgatcc ctctgtgcgg ccctctgtgg atgaaatctt
     1801 aaagaaactc tccacctttt ctaagtagtg tatcaaaatc taaaccaagg agtctctgga
     1861 caagaagctg ggagaggcac aaactggaca tctctctctc tcatatcctt cggcattggg
     1921 ttatctatgg gtgcaaggag tgggcacgct tctctgttac aaatagaaaa cgattccagt
     1981 catacaggac acatcccact ccaaatgata tttccaaaaa catacctctg acagtaactt
     2041 tgatagatgg tttgtcaaat gtatctttct gggtatccac acctcttggc aatgaaattt
     2101 gcagctcctc ccttccataa atgaagtctc tttccccacc atttgaatct gggctggcac
     2161 tgtgacttga tttgatcaat agaatgtgga agaagtgact gtatgccagt tccaagccta
     2221 ggtttcaaga ggccttataa atgtctgttg gaaccttacc cagccatgaa catgttgagt
     2281 gagcatgctg gagaatgaga gaccacatga agcagaaaca tgctttccta gctgaagtca
     2341 tactagccca accaacatgg cagctaacac atgaatgagg ccaatcaaga ccagaagaac
     2401 cactcaagca gatcccagcc caaattgccc attcacacaa tcaggagcta aataaattac
     2461 tgttgtctta acactaa
//
