LOCUS       NM_005204               2850 bp    mRNA    linear   PRI 15-OCT-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase kinase 8
            (MAP3K8), transcript variant 1, mRNA.
ACCESSION   NM_005204
VERSION     NM_005204.4
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 2850)
  AUTHORS   Sibira,R., Vu,A., Giubellino,A. and Murugan,P.
  TITLE     Spitz melanoma with MAP3K8::ABLIM1 rearrangement: a case report
            with review of the literature
  JOURNAL   Diagn Pathol 19 (1), 133 (2024)
   PUBMED   39363234
  REMARK    GeneRIF: Spitz melanoma with MAP3K8::ABLIM1 rearrangement: a case
            report with review of the literature.
            Review article
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 2850)
  AUTHORS   Bansod,S., Dodhiawala,P.B., Geng,Y., Bulle,A., Liu,P., Li,L.,
            Townsend,R., Grierson,P.M., Held,J.M., Adhikari,H. and Lim,K.H.
  TITLE     The TRIM4 E3 ubiquitin ligase degrades TPL2 and is modulated by
            oncogenic KRAS
  JOURNAL   Cell Rep 43 (9), 114667 (2024)
   PUBMED   39178114
  REMARK    GeneRIF: The TRIM4 E3 ubiquitin ligase degrades TPL2 and is
            modulated by oncogenic KRAS.
REFERENCE   3  (bases 1 to 2850)
  AUTHORS   Patel,P., Hagstrom,M., Sharma,N., Chen,A., Dhillon,S.,
            Fumero-Velazquez,M., Olivares,S. and Gerami,P.
  TITLE     Clinical, Morphologic, and Molecular Features of MAP3K8 Rearranged
            Spitz Neoplasms: A Retrospective Study Documenting That Bonafide
            Spitz Melanomas Are Rare
  JOURNAL   Am J Surg Pathol 48 (4), 437-446 (2024)
   PUBMED   38233731
  REMARK    GeneRIF: Clinical, Morphologic, and Molecular Features of MAP3K8
            Rearranged Spitz Neoplasms: A Retrospective Study Documenting That
            Bonafide Spitz Melanomas Are Rare.
REFERENCE   4  (bases 1 to 2850)
  AUTHORS   Yu,Q., Wan,D., Fu,R., Li,F. and Zhang,Y.
  TITLE     Overexpression of TPL2 may be a predictor of good prognosis in
            patients with breast invasive ductal carcinoma
  JOURNAL   Sci Rep 13 (1), 17346 (2023)
   PUBMED   37833434
  REMARK    GeneRIF: Overexpression of TPL2 may be a predictor of good
            prognosis in patients with breast invasive ductal carcinoma.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 2850)
  AUTHORS   Ballester,A., Tobena,R., Lisbona,C., Calvo,V. and Alemany,S.
  TITLE     Cot kinase regulation of IL-2 production in Jurkat T cells
  JOURNAL   J Immunol 159 (4), 1613-1618 (1997)
   PUBMED   9257820
REFERENCE   6  (bases 1 to 2850)
  AUTHORS   Salmeron,A., Ahmad,T.B., Carlile,G.W., Pappin,D., Narsimhan,R.P.
            and Ley,S.C.
  TITLE     Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel
            MAP kinase kinase kinase
  JOURNAL   EMBO J 15 (4), 817-826 (1996)
   PUBMED   8631303
REFERENCE   7  (bases 1 to 2850)
  AUTHORS   Aoki,M., Hamada,F., Sugimoto,T., Sumida,S., Akiyama,T. and
            Toyoshima,K.
  TITLE     The human cot proto-oncogene encodes two protein serine/threonine
            kinases with different transforming activities by alternative
            initiation of translation
  JOURNAL   J Biol Chem 268 (30), 22723-22732 (1993)
   PUBMED   8226782
REFERENCE   8  (bases 1 to 2850)
  AUTHORS   Chan,A.M., Chedid,M., McGovern,E.S., Popescu,N.C., Miki,T. and
            Aaronson,S.A.
  TITLE     Expression cDNA cloning of a serine kinase transforming gene
  JOURNAL   Oncogene 8 (5), 1329-1333 (1993)
   PUBMED   8479752
REFERENCE   9  (bases 1 to 2850)
  AUTHORS   Aoki,M., Akiyama,T., Miyoshi,J. and Toyoshima,K.
  TITLE     Identification and characterization of protein products of the cot
            oncogene with serine kinase activity
  JOURNAL   Oncogene 6 (9), 1515-1519 (1991)
   PUBMED   1833717
REFERENCE   10 (bases 1 to 2850)
  AUTHORS   Miyoshi,J., Higashi,T., Mukai,H., Ohuchi,T. and Kakunaga,T.
  TITLE     Structure and transforming potential of the human cot oncogene
            encoding a putative protein kinase
  JOURNAL   Mol Cell Biol 11 (8), 4088-4096 (1991)
   PUBMED   2072910
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL161651.13.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_005204.3.
            
            Summary: This gene is an oncogene that encodes a member of the
            serine/threonine protein kinase family. The encoded protein
            localizes to the cytoplasm and can activate both the MAP kinase and
            JNK kinase pathways. This protein was shown to activate IkappaB
            kinases, and thus induce the nuclear production of NF-kappaB. This
            protein was also found to promote the production of TNF-alpha and
            IL-2 during T lymphocyte activation. This gene may also utilize a
            downstream in-frame translation start codon, and thus produce an
            isoform containing a shorter N-terminus. The shorter isoform has
            been shown to display weaker transforming activity. Alternate
            splicing results in multiple transcript variants that encode the
            same protein. [provided by RefSeq, Sep 2011].
            
            Transcript Variant: This variant (1) represents the longest
            transcript. Variants 1-3 encode the same protein.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: SRR1660803.107248.1,
                                           SRR1660803.97478.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000263056.6/ ENSP00000263056.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-195               AL161651.13        116775-116969
            196-426             AL161651.13        119767-119997
            427-785             AL161651.13        121507-121865
            786-953             AL161651.13        130373-130540
            954-1215            AL161651.13        132849-133110
            1216-1322           AL161651.13        134229-134335
            1323-1475           AL161651.13        140675-140827
            1476-1722           AL161651.13        141846-142092
            1723-2850           AL161651.13        143297-144424
FEATURES             Location/Qualifiers
     source          1..2850
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="10"
                     /map="10p11.23"
     gene            1..2850
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /note="mitogen-activated protein kinase kinase kinase 8"
                     /db_xref="GeneID:1326"
                     /db_xref="HGNC:HGNC:6860"
                     /db_xref="MIM:191195"
     exon            1..195
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     exon            196..426
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     exon            427..785
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     CDS             450..1853
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /EC_number="2.7.11.25"
                     /note="cot (cancer Osaka thyroid) oncogene; Ewing sarcoma
                     transformant; proto-oncogene serine/threoine protein
                     kinase; proto-oncogene c-Cot; tumor progression locus 2;
                     augmented in rheumatoid arthritis 2"
                     /codon_start=1
                     /product="mitogen-activated protein kinase kinase kinase
                     8"
                     /protein_id="NP_005195.2"
                     /db_xref="CCDS:CCDS7166.1"
                     /db_xref="GeneID:1326"
                     /db_xref="HGNC:HGNC:6860"
                     /db_xref="MIM:191195"
                     /translation="MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEP
                     SLMTMCQDSNQNDERSKSLLLSGQEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQR
                     PQESGILLNMVITPQNGRYQIDSDVLLIPWKLTYRNIGSDFIPRGAFGKVYLAQDIKT
                     KKRMACKLIPVDQFKPSDVEIQACFRHENIAELYGAVLWGETVHLFMEAGEGGSVLEK
                     LESCGPMREFEIIWVTKHVLKGLDFLHSKKVIHHDIKPSNIVFMSTKAVLVDFGLSVQ
                     MTEDVYFPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRS
                     AYPSYLYIIHKQAPPLEDIADDCSPGMRELIEASLERNPNHRPRAADLLKHEALNPPR
                     EDQPRCQSLDSALLERKRLLSRKELELPENIADSSCTGSTEESEMLKRQRSLYIDLGA
                     LAGYFNLVRGPPTLEYG"
     exon            786..953
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     exon            954..1215
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1216..1322
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1323..1475
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1476..1722
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1723..2850
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2782..2787
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /note="hexamer: AATAAA"
     polyA_site      2806
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /note="major polyA site"
     regulatory      2828..2833
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
                     /note="hexamer: AATAAA"
     polyA_site      2850
                     /gene="MAP3K8"
                     /gene_synonym="AURA2; c-COT; COT; EST; ESTF; MEKK8; Tpl-2;
                     TPL2"
ORIGIN      
        1 actcgtccgc tccgctctgg actgcgcgcc acgctctggg gtccggcgcc ctggttcctg
       61 cttctgccgc tgccgccgcc ggatcccagt ggcccggcgt gctcggctcc cacaggcctg
      121 cagccagcat cgcaccgaac cttcgggggg ccgcggctgg agcgctcggc cggcgtggga
      181 gcgccaaggc cgcagatgca atcttcttac cgcgaagaag ccaggggaat aggtagccac
      241 atcttgtttg cagataagaa aggaagctaa cgcagtatct gcaaagccag gagtctgact
      301 cagtactttt ctcactcatg catacaaagc agctaaaaat gacacagctt atttaccatg
      361 cccctgacac tgcactgagc actttatgag cttgaactct gttaatcctc acgaccacct
      421 catgagactc tccagaaaga gcaacagtaa tggagtacat gagcactgga agtgacaata
      481 aagaagagat tgatttatta attaaacatt taaatgtgtc tgatgtaata gacattatgg
      541 aaaatcttta tgcaagtgaa gagccagcag tttatgaacc cagtctaatg accatgtgtc
      601 aagacagtaa tcaaaacgat gagcgttcta agtctctgct gcttagtggc caagaggtac
      661 catggttgtc atcagtcaga tatggaactg tggaggattt gcttgctttt gcaaaccata
      721 tatccaacac tgcaaagcat ttttatggac aacgaccaca ggaatctgga attttattaa
      781 acatggtcat cactccccaa aatggacgtt accaaataga ttccgatgtt ctcctgatcc
      841 cctggaagct gacttacagg aatattggtt ctgattttat tcctcggggc gcctttggaa
      901 aggtatactt ggcacaagat ataaagacga agaaaagaat ggcgtgtaaa ctgatcccag
      961 tagatcaatt taagccatct gatgtggaaa tccaggcttg cttccggcac gagaacatcg
     1021 cagagctgta tggcgcagtc ctgtggggtg aaactgtcca tctctttatg gaagcaggcg
     1081 agggagggtc tgttctggag aaactggaga gctgtggacc aatgagagaa tttgaaatta
     1141 tttgggtgac aaagcatgtt ctcaagggac ttgattttct acactcaaag aaagtgatcc
     1201 atcatgatat taaacctagc aacattgttt tcatgtccac aaaagctgtt ttggtggatt
     1261 ttggcctaag tgttcaaatg accgaagatg tctattttcc taaggacctc cgaggaacag
     1321 agatttacat gagcccagag gtcatcctgt gcaggggcca ttcaaccaaa gcagacatct
     1381 acagcctggg ggccacgctc atccacatgc agacgggcac cccaccctgg gtgaagcgct
     1441 accctcgctc agcctatccc tcctacctgt acataatcca caagcaagca cctccactgg
     1501 aagacattgc agatgactgc agtccaggga tgagagagct gatagaagct tccctggaga
     1561 gaaaccccaa tcaccgccca agagccgcag acctactaaa acatgaggcc ctgaacccgc
     1621 ccagagagga tcagccacgc tgtcagagtc tggactctgc cctcttggag cgcaagaggc
     1681 tgctgagtag gaaggagctg gaacttcctg agaacattgc tgattcttcg tgcacaggaa
     1741 gcaccgagga atctgagatg ctcaagaggc aacgctctct ctacatcgac ctcggcgctc
     1801 tggctggcta cttcaatctt gttcggggac caccaacgct tgaatatggc tgaaggatgc
     1861 catgtttgct ctaaattaag acagcattga tctcctggag gctggttctg ctgcctctac
     1921 acaggggccc tgtacagtga atggtgccat tttcgaagga gcagtgtgac ctcctgtgac
     1981 ccgtgaatgt gcctccaagc ggccctgtgt gtttgacatg tgaagctatt tgatatgcac
     2041 caggtctcaa ggttctcatt tctcaggtga cgtgattcta aggcaggaat ttgagagttc
     2101 acagaaggat cgtgtctgct gactgtttca ttcactgtgc actttgctca aaattttaaa
     2161 aataccaatc acaaggataa tagagtagcc taaaattact attcttggtt cttatttaag
     2221 tatggaatat tcattttact cagaatagct gttttgtgta tattggtgta tattatataa
     2281 ctctttgagc ctttattggt aaattctggt atacattgaa ttcattataa tttgggtgac
     2341 tagaacaact tgaagattgt agcaataagc tggactagtg tcctaaaaat ggctaactga
     2401 tgaattagaa gccatctgac agcaggccac tagtgacagt ttcttttgtg ttcctatgga
     2461 aacattttat actgtacatg ctatgctgaa gacattcaaa acgtgatgtt ttgaatgtgg
     2521 ataaaactgt gtaaaccaca taatttttgt acatcccaaa ggatgagaat gtgaccttta
     2581 agaaaaatga aaacttttgt aaattattga tgattttgta attcttatga ctaaattttc
     2641 ttttaagcat ttgtatatta aaatagcata ctgtgtatgt tttatatcaa atgccttcat
     2701 gaatctttca tacatatata tatttgtaac attgtaaagt atgtgagtag tcttatgtaa
     2761 agtatgtttt tacattatgc aaataaaacc caatactttt gtccaatgtg gttggtcaaa
     2821 tcaactgaat aaattcagta ttttgcctta
//
