LOCUS       NM_003010               3778 bp    mRNA    linear   PRI 19-SEP-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase 4 (MAP2K4),
            transcript variant 1, mRNA.
ACCESSION   NM_003010
VERSION     NM_003010.4
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 3778)
  AUTHORS   Pan,C., Su,Z., Xie,H., Ning,Y., Li,S. and Xiao,H.
  TITLE     Hsa_circ_0081069 facilitates tongue squamous cell carcinoma
            progression by modulating MAP2K4 expression via miR-634
  JOURNAL   Odontology 111 (2), 474-486 (2023)
   PUBMED   36181561
  REMARK    GeneRIF: Hsa_circ_0081069 facilitates tongue squamous cell
            carcinoma progression by modulating MAP2K4 expression via miR-634.
REFERENCE   2  (bases 1 to 3778)
  AUTHORS   Wang,B., Yang,S., Jia,Y., Yang,J., Du,K., Luo,Y., Li,Y., Wang,Z.,
            Liu,Y. and Zhu,B.
  TITLE     PCAT19 Regulates the Proliferation and Apoptosis of Lung Cancer
            Cells by Inhibiting miR-25-3p via Targeting the MAP2K4 Signal Axis
  JOURNAL   Dis Markers 2022, 2442094 (2022)
   PUBMED   35615401
  REMARK    GeneRIF: PCAT19 Regulates the Proliferation and Apoptosis of Lung
            Cancer Cells by Inhibiting miR-25-3p via Targeting the MAP2K4
            Signal Axis.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 3778)
  AUTHORS   Cho,N.H., Cheveralls,K.C., Brunner,A.D., Kim,K., Michaelis,A.C.,
            Raghavan,P., Kobayashi,H., Savy,L., Li,J.Y., Canaj,H., Kim,J.Y.S.,
            Stewart,E.M., Gnann,C., McCarthy,F., Cabrera,J.P., Brunetti,R.M.,
            Chhun,B.B., Dingle,G., Hein,M.Y., Huang,B., Mehta,S.B.,
            Weissman,J.S., Gomez-Sjoberg,R., Itzhak,D.N., Royer,L.A., Mann,M.
            and Leonetti,M.D.
  TITLE     OpenCell: Endogenous tagging for the cartography of human cellular
            organization
  JOURNAL   Science 375 (6585), eabi6983 (2022)
   PUBMED   35271311
REFERENCE   4  (bases 1 to 3778)
  AUTHORS   Kragelj,J., Orand,T., Delaforge,E., Tengo,L., Blackledge,M.,
            Palencia,A. and Jensen,M.R.
  TITLE     Enthalpy-Entropy Compensation in the Promiscuous Interaction of an
            Intrinsically Disordered Protein with Homologous Protein Partners
  JOURNAL   Biomolecules 11 (8), 1204 (2021)
   PUBMED   34439869
  REMARK    Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3778)
  AUTHORS   Liu,X.D., Zhang,Z.W., Wu,H.W. and Liang,Z.Y.
  TITLE     A new prognosis prediction model combining TNM stage with MAP2K4
            and JNK in postoperative pancreatic cancer patients
  JOURNAL   Pathol Res Pract 217, 153313 (2021)
   PUBMED   33341545
  REMARK    GeneRIF: A new prognosis prediction model combining TNM stage with
            MAP2K4 and JNK in postoperative pancreatic cancer patients.
REFERENCE   6  (bases 1 to 3778)
  AUTHORS   Gale,N.W., Holland,S.J., Valenzuela,D.M., Flenniken,A., Pan,L.,
            Ryan,T.E., Henkemeyer,M., Strebhardt,K., Hirai,H., Wilkinson,D.G.,
            Pawson,T., Davis,S. and Yancopoulos,G.D.
  TITLE     Eph receptors and ligands comprise two major specificity subclasses
            and are reciprocally compartmentalized during embryogenesis
  JOURNAL   Neuron 17 (1), 9-19 (1996)
   PUBMED   8755474
REFERENCE   7  (bases 1 to 3778)
  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   8  (bases 1 to 3778)
  AUTHORS   Lin,A., Minden,A., Martinetto,H., Claret,F.X., Lange-Carter,C.,
            Mercurio,F., Johnson,G.L. and Karin,M.
  TITLE     Identification of a dual specificity kinase that activates the Jun
            kinases and p38-Mpk2
  JOURNAL   Science 268 (5208), 286-290 (1995)
   PUBMED   7716521
REFERENCE   9  (bases 1 to 3778)
  AUTHORS   Derijard,B., Raingeaud,J., Barrett,T., Wu,I.H., Han,J.,
            Ulevitch,R.J. and Davis,R.J.
  TITLE     Independent human MAP-kinase signal transduction pathways defined
            by MEK and MKK isoforms
  JOURNAL   Science 267 (5198), 682-685 (1995)
   PUBMED   7839144
  REMARK    Erratum:[Science 1995 Jul 7;269(5220):17]
REFERENCE   10 (bases 1 to 3778)
  AUTHORS   Yan,M., Dai,T., Deak,J.C., Kyriakis,J.M., Zon,L.I., Woodgett,J.R.
            and Templeton,D.J.
  TITLE     Activation of stress-activated protein kinase by MEKK1
            phosphorylation of its activator SEK1
  JOURNAL   Nature 372 (6508), 798-800 (1994)
   PUBMED   7997270
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC036032.1, L36870.1,
            BQ028457.1 and AU150695.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_003010.3.
            
            Summary: This gene encodes a member of the mitogen-activated
            protein kinase (MAPK) family. Members of this family act as an
            integration point for multiple biochemical signals and are involved
            in a wide variety of cellular processes such as proliferation,
            differentiation, transcription regulation, and development. They
            form a three-tiered signaling module composed of MAPKKKs, MAPKKs,
            and MAPKs. This protein is phosphorylated at serine and threonine
            residues by MAPKKKs and subsequently phosphorylates downstream MAPK
            targets at threonine and tyrosine residues. A similar protein in
            mouse has been reported to play a role in liver organogenesis. A
            pseudogene of this gene is located on the long arm of chromosome X.
            Alternative splicing results in multiple transcript variants.
            [provided by RefSeq, Jul 2013].
            
            Transcript Variant: This variant (1) encodes 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 :: SRR1803614.39130.1, BC060764.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000353533.10/ ENSP00000262445.5
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1                 BC036032.1         60-60
            2-1610              L36870.1           1-1609
            1611-2537           BC036032.1         1670-2596
            2538-3227           L36870.1           2537-3226
            3228-3766           BQ028457.1         18-556              c
            3767-3778           AU150695.1         7-18                c
FEATURES             Location/Qualifiers
     source          1..3778
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17p12"
     gene            1..3778
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /note="mitogen-activated protein kinase kinase 4"
                     /db_xref="GeneID:6416"
                     /db_xref="HGNC:HGNC:6844"
                     /db_xref="MIM:601335"
     exon            1..125
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     CDS             11..1210
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /EC_number="2.7.12.2"
                     /note="isoform 1 is encoded by transcript variant 1; dual
                     specificity mitogen-activated protein kinase kinase 4; MAP
                     kinase kinase 4; c-Jun N-terminal kinase kinase 1;
                     SAPK/ERK kinase 1; MAPK/ERK kinase 4; JNK-activated kinase
                     1; MEK 4; MAPKK 4; JNK-activating kinase 1;
                     stress-activated protein kinase kinase 1; c-Jun
                     NH2-terminal kinase kinase 1"
                     /codon_start=1
                     /product="dual specificity mitogen-activated protein
                     kinase kinase 4 isoform 1"
                     /protein_id="NP_003001.1"
                     /db_xref="CCDS:CCDS11162.1"
                     /db_xref="GeneID:6416"
                     /db_xref="HGNC:HGNC:6844"
                     /db_xref="MIM:601335"
                     /translation="MAAPSPSGGGGSGGGSGSGTPGPVGSPAPGHPAVSSMQGKRKAL
                     KLNFANPPFKSTARFTLNPNPTGVQNPHIERLRTHSIESSGKLKISPEQHWDFTAEDL
                     KDLGEIGRGAYGSVNKMVHKPSGQIMAVKRIRSTVDEKEQKQLLMDLDVVMRSSDCPY
                     IVQFYGALFREGDCWICMELMSTSFDKFYKYVYSVLDDVIPEEILGKITLATVKALNH
                     LKENLKIIHRDIKPSNILLDRSGNIKLCDFGISGQLVDSIAKTRDAGCRPYMAPERID
                     PSASRQGYDVRSDVWSLGITLYELATGRFPYPKWNSVFDQLTQVVKGDPPQLSNSEER
                     EFSPSFINFVNLCLTKDESKRPKYKELLKHPFILMYEERAVEVACYVCKILDQMPATP
                     SSPMYVD"
     exon            126..228
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            229..403
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            404..523
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            524..643
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            644..695
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            696..823
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            824..901
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            902..1050
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1051..1096
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1097..3778
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1874..1879
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /note="hexamer: ATTAAA"
     polyA_site      1893
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
     regulatory      3661..3666
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /note="hexamer: AATAAA"
     polyA_site      3684
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
     regulatory      3745..3750
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /note="hexamer: ATTAAA"
     polyA_site      3778
                     /gene="MAP2K4"
                     /gene_synonym="JNKK; JNKK1; MAPKK4; MEK4; MKK4; PRKMK4;
                     SAPKK-1; SAPKK1; SEK1; SERK1; SKK1"
                     /note="major polyA site"
ORIGIN      
        1 actcccaaca atggcggctc cgagcccgag cggcggcggc ggctccgggg gcggcagcgg
       61 cagcggcacc cccggccccg tagggtcccc ggcgccaggc cacccggccg tcagcagcat
      121 gcagggtaaa cgcaaagcac tgaagttgaa ttttgcaaat ccacctttca aatctacagc
      181 aaggtttact ctgaatccca atcctacagg agttcaaaac ccacacatag agagactgag
      241 aacacacagc attgagtcat caggaaaact gaagatctcc cctgaacaac actgggattt
      301 cactgcagag gacttgaaag accttggaga aattggacga ggagcttatg gttctgtcaa
      361 caaaatggtc cacaaaccaa gtgggcaaat aatggcagtt aaaagaattc ggtcaacagt
      421 ggatgaaaaa gaacaaaaac aacttcttat ggatttggat gtagtaatgc ggagtagtga
      481 ttgcccatac attgttcagt tttatggtgc actcttcaga gagggtgact gttggatctg
      541 tatggaactc atgtctacct cgtttgataa gttttacaaa tatgtatata gtgtattaga
      601 tgatgttatt ccagaagaaa ttttaggcaa aatcacttta gcaactgtga aagcactaaa
      661 ccacttaaaa gaaaacttga aaattattca cagagatatc aaaccttcca atattcttct
      721 ggacagaagt ggaaatatta agctctgtga cttcggcatc agtggacagc ttgtggactc
      781 tattgccaag acaagagatg ctggctgtag gccatacatg gcacctgaaa gaatagaccc
      841 aagcgcatca cgacaaggat atgatgtccg ctctgatgtc tggagtttgg ggatcacatt
      901 gtatgagttg gccacaggcc gatttcctta tccaaagtgg aatagtgtat ttgatcaact
      961 aacacaagtc gtgaaaggag atcctccgca gctgagtaat tctgaggaaa gggaattctc
     1021 cccgagtttc atcaactttg tcaacttgtg ccttacgaag gatgaatcca aaaggccaaa
     1081 gtataaagag cttctgaaac atccctttat tttgatgtat gaagaacgtg ccgttgaggt
     1141 cgcatgctat gtttgtaaaa tcctggatca aatgccagct actcccagct ctcccatgta
     1201 tgtcgattga tatcgctgct acatcagact ctagaaaaaa gggctgagag gaagcaagac
     1261 gtaaagaatt ttcatcccgt atcacagtgt ttttattgct cgcccagaca ccatgtgcaa
     1321 taagattggt gttcgtttcc atcatgtctg tatactcctg tcacctagaa cgtgcatcct
     1381 tgtaatacct gattgatcac acagtgttag tgctggtcag agagacctca tcctgctctt
     1441 ttgtgatgaa catattcatg aaatgtggaa gtcagtacga tcaagttgtt gactgtgatt
     1501 agatcacatc ttaaattcat ttctagactc aaaacctgga gatgcagcta ctggaatggt
     1561 gttttgtcag acttccaaat cctggaagga cacagtgatg aatgtactat gtctgaacat
     1621 agaaactcgg gcttgagtga gaagagcttg cacagccaac gagacacatt gccttctgga
     1681 gctgggagac aaaggaggaa tttactttct tcaccaagtg caatagatta ctgatgtgat
     1741 attctgttgc tttacagtta cagttgatgt ttggggatcg atgtgctcag ccaaatttcc
     1801 tgtttgaaat atcatgttaa attagaatga atttatcttt accaaaaacc atgttgcgtt
     1861 caaagaggtg aacattaaaa tatagagaca ggacagaatg tgttcttttc tcctttacca
     1921 gtcctatttt tcaatgggaa gactcaggag tctgccactt gtcaaagaag gtgctgatcc
     1981 taagaatttt tcattctcag aattcggtgt gctgccaact tgatgttcca cctgccacaa
     2041 accaccagga ctgaaagaag aaaacagtac agaaggcaaa gtttacagat gtttttaatt
     2101 ctagtatttt atctggaaca acttgtagca gctatatatt tccccttggt cccaagcctg
     2161 atactttagc catcataact cactaacagg gagaagtagc tagtagcaat gtgccttgat
     2221 tgattagata aagatttcta gtaggcagca aaagaccaaa tctcagttgt ttgcttcttg
     2281 ccatcactgg tccaggtctt cagtttccga atctctttcc cttcccctgt ggtctattgt
     2341 cgctatgtga cttgcgctta atccaatatt ttgccttttt tctatatcaa aaaaccttta
     2401 cagttagcag ggatgttcct taccaaggat ttttagcccc aaatctctca tattcgctag
     2461 tgtttaaaag gctaagaata gtggggccca gccgatgtgg taggtgataa agaggcatct
     2521 tttctagaga cacattggac cagatgagga tccgaaacgg cagcctttac gttcatcacc
     2581 tgctagaacc tctcgtagtc catcaccatt tcttggcatt ggaattctac tggaaaaaaa
     2641 tacaaaaagc aaaacaaaac cctcagcact gttacaagag gccatttaag tatcttgtgc
     2701 ttcttcactt acccattagc caggttctca ttaggttttg cttgggcctc cctggcactg
     2761 aaccttaggc tttgtatgac agtgaagcag cactgtgagt ggttcaagca cactggaata
     2821 taaaacagtc atggcctgag atgcaggtga tgccattaca gaaccaaatc gtggcacgta
     2881 ttgctgtgtc tcctctcaga gtgacagtca taaatactgt caaacaataa agggagaatg
     2941 gtgctgttta aagtcacatc cctgtaaatt gcagaattca aaagtgatta tctctttgat
     3001 ctacttgcct catttcccta tcttctcccc cacggtatcc taaactttag acttcccact
     3061 gttctgaaag gagacattgc tctatgtctg ccttcgacca cagcaagcca tcatcctcca
     3121 ttgctcccgg ggactcaaga ggaatctgtt tctctgctgt caacttccca tctggctcag
     3181 catagggtca ctttgccatt atgcaaatgg agataaaagc aattctgact gtccaggagc
     3241 taatctgacc gttctattgt gtggatgacc acataagaag gcaattttag tgtattaatc
     3301 atagattatt ataaactata aacttaaggg caaggagttt attacaatgt atctttatta
     3361 aaacaaaagg gtgtatagtg ttcacaaact gtgaaaatag tgtaagaact gtacattgtg
     3421 agctctggtt atttttctct tgtaccatag aaaaatgtat aaaaattatc aaaaagctaa
     3481 tgtgcaggga tattgcctta tttgtctgta aaaaatggag ctcagtaaca taactgcttc
     3541 ttggagcttt ggaatatttt atcctgtatt cttgtttgaa ttcctcctct atttaagata
     3601 tatacatgga atcgaagtgt ttatgtaata gttctatcct tttgcctgca ggtcagttgt
     3661 aataaatcta ggatgtgatg atgactttgt aatttgattt tctgaaatca gaccctgaga
     3721 ggggaaaatc ttaaagtaaa ttacattaaa ttatctgtgc atttcacacc agggaaaa
//
