LOCUS       NM_001193511            4261 bp    mRNA    linear   PRI 11-FEB-2025
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase kinase 12
            (MAP3K12), transcript variant 1, mRNA.
ACCESSION   NM_001193511
VERSION     NM_001193511.2
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 4261)
  AUTHORS   Kennedy,S.A., Jarboui,M.A., Srihari,S., Raso,C., Bryan,K.,
            Dernayka,L., Charitou,T., Bernal-Llinares,M., Herrera-Montavez,C.,
            Krstic,A., Matallanas,D., Kotlyar,M., Jurisica,I., Curak,J.,
            Wong,V., Stagljar,I., LeBihan,T., Imrie,L., Pillai,P., Lynn,M.A.,
            Fasterius,E., Al-Khalili Szigyarto,C., Breen,J., Kiel,C.,
            Serrano,L., Rauch,N., Rukhlenko,O., Kholodenko,B.N.,
            Iglesias-Martinez,L.F., Ryan,C.J., Pilkington,R., Cammareri,P.,
            Sansom,O., Shave,S., Auer,M., Horn,N., Klose,F., Ueffing,M.,
            Boldt,K., Lynn,D.J. and Kolch,W.
  TITLE     Extensive rewiring of the EGFR network in colorectal cancer cells
            expressing transforming levels of KRASG13D
  JOURNAL   Nat Commun 11 (1), 499 (2020)
   PUBMED   31980649
  REMARK    Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4261)
  AUTHORS   Yu,J., Feng,Y., Wang,Y. and An,R.
  TITLE     Aryl hydrocarbon receptor enhances the expression of miR-150-5p to
            suppress in prostate cancer progression by regulating MAP3K12
  JOURNAL   Arch Biochem Biophys 654, 47-54 (2018)
   PUBMED   30009782
  REMARK    GeneRIF: Aryl hydrocarbon receptor enhances the expression of
            miR-150-5p to suppress cell proliferation and invasion in prostate
            cancer by regulating MAP3K12
REFERENCE   3  (bases 1 to 4261)
  AUTHORS   Welsbie,D.S., Mitchell,K.L., Jaskula-Ranga,V., Sluch,V.M., Yang,Z.,
            Kim,J., Buehler,E., Patel,A., Martin,S.E., Zhang,P.W., Ge,Y.,
            Duan,Y., Fuller,J., Kim,B.J., Hamed,E., Chamling,X., Lei,L.,
            Fraser,I.D.C., Ronai,Z.A., Berlinicke,C.A. and Zack,D.J.
  TITLE     Enhanced Functional Genomic Screening Identifies Novel Mediators of
            Dual Leucine Zipper Kinase-Dependent Injury Signaling in Neurons
  JOURNAL   Neuron 94 (6), 1142-1154 (2017)
   PUBMED   28641113
  REMARK    GeneRIF: LZK cooperates with DLK to promote retinal ganglion cell
            death in response to axon injury.
REFERENCE   4  (bases 1 to 4261)
  AUTHORS   Huang,Y.A., Zhou,B., Wernig,M. and Sudhof,T.C.
  TITLE     ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription
            and Abeta Secretion
  JOURNAL   Cell 168 (3), 427-441 (2017)
   PUBMED   28111074
REFERENCE   5  (bases 1 to 4261)
  AUTHORS   Oetjen,E.
  TITLE     Regulation of Beta-Cell Function and Mass by the Dual Leucine
            Zipper Kinase
  JOURNAL   Arch Pharm (Weinheim) 349 (6), 410-413 (2016)
   PUBMED   27100796
  REMARK    GeneRIF: REVIEW: Regulation of Beta-Cell Function and Mass by the
            Dual Leucine Zipper Kinase
            Review article
REFERENCE   6  (bases 1 to 4261)
  AUTHORS   Mata,M., Merritt,S.E., Fan,G., Yu,G.G. and Holzman,L.B.
  TITLE     Characterization of dual leucine zipper-bearing kinase, a mixed
            lineage kinase present in synaptic terminals whose phosphorylation
            state is regulated by membrane depolarization via calcineurin
  JOURNAL   J Biol Chem 271 (28), 16888-16896 (1996)
   PUBMED   8663324
REFERENCE   7  (bases 1 to 4261)
  AUTHORS   Hirai,S., Izawa,M., Osada,S., Spyrou,G. and Ohno,S.
  TITLE     Activation of the JNK pathway by distantly related protein kinases,
            MEKK and MUK
  JOURNAL   Oncogene 12 (3), 641-650 (1996)
   PUBMED   8637721
REFERENCE   8  (bases 1 to 4261)
  AUTHORS   Reddy,U.R., Nycum,L., Slavc,I. and Biegel,J.A.
  TITLE     Localization of the human zipper protein kinase gene (ZPK) to
            chromosome 12q13 by fluorescence in situ hybridization and somatic
            cell hybrid analysis
  JOURNAL   Genomics 25 (2), 597-598 (1995)
   PUBMED   7790002
REFERENCE   9  (bases 1 to 4261)
  AUTHORS   Holzman,L.B., Merritt,S.E. and Fan,G.
  TITLE     Identification, molecular cloning, and characterization of dual
            leucine zipper bearing kinase. A novel serine/threonine protein
            kinase that defines a second subfamily of mixed lineage kinases
  JOURNAL   J Biol Chem 269 (49), 30808-30817 (1994)
   PUBMED   7983011
REFERENCE   10 (bases 1 to 4261)
  AUTHORS   Reddy,U.R. and Pleasure,D.
  TITLE     Cloning of a novel putative protein kinase having a leucine zipper
            domain from human brain
  JOURNAL   Biochem Biophys Res Commun 202 (1), 613-620 (1994)
   PUBMED   8037767
  REMARK    Erratum:[Biochem Biophys Res Commun. 1994 Dec 15;205(2):1494-5.
            doi: 10.1006/bbrc.1994.2834.. PMID: 7802686]
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC050050.1, AK094195.1 and
            AC023509.42.
            
            On Nov 23, 2018 this sequence version replaced NM_001193511.1.
            
            Summary: This gene encodes a member of the serine/threonine protein
            kinase family. This kinase contains a leucine-zipper domain and is
            predominately expressed in neuronal cells. The phosphorylation
            state of this kinase in synaptic terminals was shown to be
            regulated by membrane depolarization via calcineurin. This kinase
            forms heterodimers with leucine zipper containing transcription
            factors, such as cAMP responsive element binding protein (CREB) and
            MYC, and thus may play a regulatory role in PKA or retinoic acid
            induced neuronal differentiation. Alternatively spliced transcript
            variants encoding different proteins have been described.[provided
            by RefSeq, Jul 2010].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            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 :: SRR1660809.179053.1,
                                           SRR1660803.227057.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000547488.6/ ENSP00000449038.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1602              BC050050.1         204-1805
            1603-2809           AK094195.1         1601-2807
            2810-4261           AC023509.42        141650-143101
FEATURES             Location/Qualifiers
     source          1..4261
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q13.13"
     gene            1..4261
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /note="mitogen-activated protein kinase kinase kinase 12"
                     /db_xref="GeneID:7786"
                     /db_xref="HGNC:HGNC:6851"
                     /db_xref="MIM:600447"
     exon            1..32
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            33..514
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     CDS             70..2748
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /EC_number="2.7.11.25"
                     /note="isoform 1 is encoded by transcript variant 1;
                     protein kinase MUK; dual leucine zipper kinase DLK;
                     leucine zipper protein kinase; MAPK-upstream kinase; mixed
                     lineage kinase; dual leucine zipper bearing kinase"
                     /codon_start=1
                     /product="mitogen-activated protein kinase kinase kinase
                     12 isoform 1"
                     /protein_id="NP_001180440.1"
                     /db_xref="CCDS:CCDS55831.1"
                     /db_xref="GeneID:7786"
                     /db_xref="HGNC:HGNC:6851"
                     /db_xref="MIM:600447"
                     /translation="MACLHETRTPSPSFGGFVSTLSEASMRKLDPDTSDCTPEKDLTP
                     TQCVLRDVVPLGGQGGGGPSPSPGGEPPPEPFANSVLQLHEQDAGGPGGAAGSPESRA
                     SRVRADEVRLQCQSGSGFLEGLFGCLRPVWTMIGKAYSTEHKQQQEDLWEVPFEEILD
                     LQWVGSGAQGAVFLGRFHGEEVAVKKVRDLKETDIKHLRKLKHPNIITFKGVCTQAPC
                     YCILMEFCAQGQLYEVLRAGRPVTPSLLVDWSMGIAGGMNYLHLHKIIHRDLKSPNML
                     ITYDDVVKISDFGTSKELSDKSTKMSFAGTVAWMAPEVIRNEPVSEKVDIWSFGVVLW
                     ELLTGEIPYKDVDSSAIIWGVGSNSLHLPVPSSCPDGFKILLRQCWNSKPRNRPSFRQ
                     ILLHLDIASADVLSTPQETYFKSQAEWREEVKLHFEKIKSEGTCLHRLEEELVMRRRE
                     ELRHALDIREHYERKLERANNLYMELNALMLQLELKERELLRREQALERRCPGLLKPH
                     PSRGLLHGNTMEKLIKKRNVPQKLSPHSKRPDILKTESLLPKLDAALSGVGLPGCPKG
                     PPSPGRSRRGKTRHRKASAKGSCGDLPGLRTAVPPHEPGGPGSPGGLGGGPSAWEACP
                     PALRGLHHDLLLRKMSSSSPDLLSAALGSRGRGATGGAGDPGSPPPARGDTPPSEGSA
                     PGSTSPDSPGGAKGEPPPPVGPGEGVGLLGTGREGTSGRGGSRAGSQHLTPAALLYRA
                     AVTRSQKRGISSEEEEGEVDSEVELTSSQRWPQSLNMRQSLSTFSSENPSDGEEGTAS
                     EPSPSGTPEVGSTNTDERPDERSDDMCSQGSEIPLDPPPSEVIPGPEPSSLPIPHQEL
                     LRERGPPNSEDSDCDSTELDNSNSVDALRPPASLPP"
     exon            515..698
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            699..890
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            891..1049
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1050..1208
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1209..1317
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1318..1427
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1428..1544
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1545..1682
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            1683..2307
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2308..2378
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2379..2649
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     exon            2650..4261
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3415..3420
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /note="hexamer: AATATA"
     polyA_site      3438
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /note="major polyA site"
     polyA_site      4261
                     /gene="MAP3K12"
                     /gene_synonym="DLK; HP09298; MEKK12; MUK; ZPK; ZPKP1"
                     /note="major polyA site"
ORIGIN      
        1 gccttttgtg ctgcggccgc ggagcccccg agggcccagt gttcaccatc ataccagggg
       61 ccagaggcga tggcttgcct ccatgagacc cgaacaccct ctccttcctt tgggggcttt
      121 gtgtctaccc taagtgaggc atccatgcgc aagctggacc cagacacttc tgactgcact
      181 cccgagaagg acctgacgcc tacccagtgt gtacttcgag atgtggtacc ccttggtggg
      241 cagggtgggg gagggcccag cccctcccca ggtggagagc cgccccctga gccttttgcc
      301 aacagtgtcc tgcagctaca tgagcaggat gcagggggcc cagggggagc agctgggtca
      361 cctgagagtc gggcatccag agttcgagct gacgaggtgc gactgcagtg ccagagtggc
      421 agtggcttcc ttgagggcct ctttggctgc ctgcgccctg tctggaccat gattggcaaa
      481 gcctactcca ctgagcacaa gcagcagcag gaagaccttt gggaggtccc ctttgaggaa
      541 atcctggacc tgcagtgggt gggctcaggg gcccagggtg ctgtcttcct ggggcgcttc
      601 cacggggagg aggtggctgt gaagaaggtg cgagacctca aagaaaccga catcaagcac
      661 ttgcgaaagc tgaagcaccc caacatcatc actttcaagg gtgtgtgcac ccaggctccc
      721 tgctactgca tcctcatgga gttctgcgcc cagggccagc tgtatgaggt actgcgggct
      781 ggccgccctg tcaccccctc cttactggtt gactggtcca tgggcatcgc tggtggcatg
      841 aactacctgc acctgcacaa gattatccac agggatctca agtcacccaa catgctaatc
      901 acctacgacg atgtggtgaa gatctcagat tttggcactt ccaaggagct gagtgacaag
      961 agcaccaaga tgtcctttgc agggacagta gcctggatgg cccctgaggt gatccgcaat
     1021 gaacctgtgt ctgagaaggt cgacatctgg tcctttggcg tggtgctatg ggaactgctg
     1081 actggtgaga tcccctacaa agacgtagat tcctcagcca ttatctgggg tgtgggaagc
     1141 aacagtctcc atctgcccgt gccctccagt tgcccagatg gtttcaagat cctgcttcgc
     1201 cagtgctgga atagcaaacc acgaaatcgc ccatcattcc gacagatcct gctgcatctg
     1261 gacattgcct cagctgatgt actctccaca ccccaggaga cttactttaa gtcccaggca
     1321 gagtggcggg aagaagtaaa actgcacttt gaaaagatta agtcagaagg gacctgtctg
     1381 caccgcctag aagaggaact ggtgatgagg aggagggagg agctcagaca cgccctggac
     1441 atcagggagc actatgaaag gaagctggag agagccaaca acctgtatat ggaacttaat
     1501 gccctcatgt tgcagctgga actcaaggag agggagctgc tcaggcgaga gcaagcttta
     1561 gagcggaggt gcccaggcct gctgaagcca cacccttccc ggggcctcct gcatggaaac
     1621 acaatggaga agcttatcaa gaagaggaat gtgccacaga agctgtcacc ccatagcaaa
     1681 aggccagata tcctcaagac ggagtctttg ctccctaaac tagatgcagc cctgagtggg
     1741 gtggggcttc ctgggtgtcc taagggcccc ccctcaccag gacggagtcg ccgtggcaag
     1801 acccgtcacc gcaaggccag cgccaagggg agctgtgggg acctgcctgg gcttcgtaca
     1861 gctgtgccac cccatgaacc tggaggacca ggaagcccag ggggcctagg agggggaccc
     1921 tcagcctggg aggcctgccc tcccgccctc cgtgggcttc atcatgacct cctgctccgc
     1981 aaaatgtctt catcgtcccc agacctgctg tcagcagcac tagggtcccg gggccggggg
     2041 gccacaggcg gagctgggga tcctggctca ccacctccgg cccggggtga caccccacca
     2101 agtgagggct cagcccctgg ctccaccagc ccagattcac ctgggggagc caaaggggaa
     2161 ccacctcctc cagtagggcc tggtgaaggt gtggggcttc tgggaactgg aagggaaggg
     2221 acctcaggcc ggggaggaag ccgggctggg tcccagcact tgaccccagc tgcactgctg
     2281 tacagggctg ccgtcacccg aagtcagaaa cgtggcatct catcggaaga ggaggaagga
     2341 gaggtagaca gtgaagtaga gctgacatca agccagaggt ggcctcagag cctgaacatg
     2401 cgccagtcac tatctacctt cagctcagag aatccatcag atggggagga aggcacagct
     2461 agtgaacctt cccccagtgg cacacctgaa gttggcagca ccaacactga tgagcggcca
     2521 gatgagcggt ctgatgacat gtgctcccag ggctcagaaa tcccactgga cccacctcct
     2581 tcagaggtca tccctggccc tgaacccagc tccctgccca ttccacacca ggaacttctc
     2641 agagagcggg gccctcccaa ttctgaggac tcagactgtg acagcactga attggacaac
     2701 tccaacagcg ttgatgcctt gcggccccca gcttccctcc ctccatgaaa gccactcgta
     2761 ttccttgtac atagagaaat atttatataa attatatata tatacatata tatatatata
     2821 tgcgccacat aatcaacaga aagatggggc tgtcccagcc gtaagtcagg ctcgagggag
     2881 actgatcccc tgaccaattc acctgataaa ctctagggac actggcagct gtggaaatga
     2941 atgaggcaca gccgtagagc tgtggctaag ggcaagcccc ttcctgcccc accccattcc
     3001 ttatattcag caagcaacaa ggcaatagaa aagccagggt tgtctttata ttctttatcc
     3061 ccaaataata gggggtgggg ggaggggcgg tgggaggggc aggagagaaa accacttaga
     3121 ctgcactttt ctgttccgtt tactctgttt acacattttg cacttgggag gagggaggct
     3181 aaggctgggt cctcccctct gaggtttctc aggtggcaat gtaactcatt tttttgtccc
     3241 accatttatc ttctctgccc aagccctgtc ttaaggccca gggggaggtt aggagactga
     3301 tagcatgtga tggctcaggc tgaagaaccg gggtgctgtt taagtccctg cttttatcct
     3361 ggtgcctgat tggggtgggg actgtcctac tgtaacccct gtgaaaaacc ttgaaatata
     3421 acactccatg caggcccagc tgttgagggt tttcttgatg aatgaatggg gtaccataca
     3481 tggttaagat aaagccttgg gctccggact ttatctgagg tgtctggaga agttctcctg
     3541 cccctccact tttttgcatc tactctcact aaatgagtat aatgtcaagc cccaactttc
     3601 taaaattata ggaataaatg gtagcagata catccttcta acttgttatg gaggactata
     3661 aatgaagtta ctaaaaacaa tagactgaaa tttttagttt aaaatatgca agcctgaaca
     3721 aggggaccaa cattcccaag aaactggaac ccagtcagac atatgatcaa ctgcttaatg
     3781 tgtatgccat gtatgtcatg tgtcattcct ttcccccacc ccctccctag tggaagtgct
     3841 tgcctactcc cctaggacag gtaagtcctc ggaaagtcta atcctcaatc ttttgggcac
     3901 aagttttata agggccaacc aagcatggag tcagggaaaa ataggatcga gggccacaaa
     3961 aaaagatgga agtggtaaaa tagaagaaaa catcttaacc ggaataaagg cttccattca
     4021 aaacccaaga agggtccttt gagggataaa aggtacaaaa ataacagcaa gacaagagga
     4081 ataaaaccca catgaatcac tgtggcatcc agtttctatt cacaaagaaa aagctccagt
     4141 ccatctttta atttttttga aaaattcctg acattacaga actaaactga aatgtattaa
     4201 tattccactc ttacatttcc atgacaaaca gaaaaattca tgagccaaaa aaaaaaaacc
     4261 a
//
