LOCUS       NM_145160               2344 bp    mRNA    linear   PRI 05-APR-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase 5 (MAP2K5),
            transcript variant 1, mRNA.
ACCESSION   NM_145160
VERSION     NM_145160.3
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 2344)
  AUTHORS   Qiu,M., Lin,Q., Liu,Y., Chen,P., Zhou,Y., Jiang,Y., Zhou,Z.,
            Wen,Q., Zhou,X., Liang,X., Gan,H. and Yu,H.
  TITLE     Potentially functional genetic variants in RPS6KA4 and MAP2K5 in
            the MAPK signaling pathway predict HBV-related hepatocellular
            carcinoma survival
  JOURNAL   Mol Carcinog 62 (9), 1378-1387 (2023)
   PUBMED   37278562
  REMARK    GeneRIF: Potentially functional genetic variants in RPS6KA4 and
            MAP2K5 in the MAPK signaling pathway predict HBV-related
            hepatocellular carcinoma survival.
REFERENCE   2  (bases 1 to 2344)
  AUTHORS   Fukasawa,K., Lyu,J., Kubo,T., Tanaka,Y., Suzuki,A., Horie,T.,
            Tomizawa,A., Osumi,R., Iwahashi,S., Tokumura,K., Murata,M.,
            Kobayashi,M., Todo,T., Hirao,A. and Hinoi,E.
  TITLE     MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma
            Stem Cells
  JOURNAL   Cancer Res Commun 3 (1), 148-159 (2023)
   PUBMED   36968222
  REMARK    GeneRIF: MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of
            Glioma Stem Cells.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2344)
  AUTHORS   Li,F., Peng,X., Zhou,J., Chen,Q. and Chen,Y.
  TITLE     Aberrant MEK5 signalling promotes clear cell renal cell carcinoma
            development via mTOR activation
  JOURNAL   J Cancer Res Clin Oncol 148 (12), 3257-3266 (2022)
   PUBMED   35713705
  REMARK    GeneRIF: Aberrant MEK5 signalling promotes clear cell renal cell
            carcinoma development via mTOR activation.
REFERENCE   4  (bases 1 to 2344)
  AUTHORS   Zhao,W., Yu,D., Chen,Z., Yao,W., Yang,J., Ramalingam,S.S. and
            Sun,S.Y.
  TITLE     Inhibition of MEK5/ERK5 signaling overcomes acquired resistance to
            the third generation EGFR inhibitor, osimertinib, via enhancing
            Bim-dependent apoptosis
  JOURNAL   Cancer Lett 519, 141-149 (2021)
   PUBMED   34245854
  REMARK    GeneRIF: Inhibition of MEK5/ERK5 signaling overcomes acquired
            resistance to the third generation EGFR inhibitor, osimertinib, via
            enhancing Bim-dependent apoptosis.
REFERENCE   5  (bases 1 to 2344)
  AUTHORS   Tusa,I., Gagliardi,S., Tubita,A., Pandolfi,S., Menconi,A.,
            Lulli,M., Dello Sbarba,P., Stecca,B. and Rovida,E.
  TITLE     The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and
            Activation in Melanoma Cells
  JOURNAL   Int J Mol Sci 22 (20), 11259 (2021)
   PUBMED   34681917
  REMARK    GeneRIF: The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression
            and Activation in Melanoma Cells.
            Publication Status: Online-Only
REFERENCE   6  (bases 1 to 2344)
  AUTHORS   Chao,T.H., Hayashi,M., Tapping,R.I., Kato,Y. and Lee,J.D.
  TITLE     MEKK3 directly regulates MEK5 activity as part of the big
            mitogen-activated protein kinase 1 (BMK1) signaling pathway
  JOURNAL   J Biol Chem 274 (51), 36035-36038 (1999)
   PUBMED   10593883
REFERENCE   7  (bases 1 to 2344)
  AUTHORS   English,J.M., Pearson,G., Hockenberry,T., Shivakumar,L., White,M.A.
            and Cobb,M.H.
  TITLE     Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and
            growth control
  JOURNAL   J Biol Chem 274 (44), 31588-31592 (1999)
   PUBMED   10531364
REFERENCE   8  (bases 1 to 2344)
  AUTHORS   Kato,Y., Tapping,R.I., Huang,S., Watson,M.H., Ulevitch,R.J. and
            Lee,J.D.
  TITLE     Bmk1/Erk5 is required for cell proliferation induced by epidermal
            growth factor
  JOURNAL   Nature 395 (6703), 713-716 (1998)
   PUBMED   9790194
REFERENCE   9  (bases 1 to 2344)
  AUTHORS   Kato,Y., Kravchenko,V.V., Tapping,R.I., Han,J., Ulevitch,R.J. and
            Lee,J.D.
  TITLE     BMK1/ERK5 regulates serum-induced early gene expression through
            transcription factor MEF2C
  JOURNAL   EMBO J 16 (23), 7054-7066 (1997)
   PUBMED   9384584
REFERENCE   10 (bases 1 to 2344)
  AUTHORS   Zhou,G., Bao,Z.Q. and Dixon,J.E.
  TITLE     Components of a new human protein kinase signal transduction
            pathway
  JOURNAL   J Biol Chem 270 (21), 12665-12669 (1995)
   PUBMED   7759517
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC016355.8, AC103753.2 and
            AC009292.11.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_145160.2.
            
            Summary: The protein encoded by this gene is a dual specificity
            protein kinase that belongs to the MAP kinase kinase family. This
            kinase specifically interacts with and activates MAPK7/ERK5. This
            kinase itself can be phosphorylated and activated by MAP3K3/MEKK3,
            as well as by atypical protein kinase C isoforms (aPKCs). The
            signal cascade mediated by this kinase is involved in growth factor
            stimulated cell proliferation and muscle cell differentiation.
            Three alternatively spliced transcript variants of this gene
            encoding distinct isoforms have been described. [provided by
            RefSeq, May 2011].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (A).
            
            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 :: BC008838.2, SRR11853567.10419.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000178640.10/ ENSP00000178640.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-768               AC016355.8         44963-45730         c
            769-817             AC016355.8         38351-38399         c
            818-885             AC016355.8         25083-25150         c
            886-955             AC016355.8         7610-7679           c
            956-996             AC016355.8         2503-2543           c
            997-1064            AC016355.8         1520-1587           c
            1065-1113           AC103753.2         69378-69426
            1114-1178           AC103753.2         77137-77201
            1179-1218           AC103753.2         107340-107379
            1219-1287           AC103753.2         122683-122751
            1288-1369           AC103753.2         122840-122921
            1370-1431           AC103753.2         135005-135066
            1432-1480           AC103753.2         141049-141097
            1481-1554           AC103753.2         168931-169004
            1555-1605           AC103753.2         169970-170020
            1606-1639           AC103753.2         179789-179822
            1640-1677           AC009292.11        19047-19084
            1678-1707           AC009292.11        43592-43621
            1708-1734           AC009292.11        63907-63933
            1735-1767           AC009292.11        64245-64277
            1768-1829           AC009292.11        85278-85339
            1830-1875           AC009292.11        88383-88428
            1876-2344           AC009292.11        122322-122790
FEATURES             Location/Qualifiers
     source          1..2344
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q23"
     gene            1..2344
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /note="mitogen-activated protein kinase kinase 5"
                     /db_xref="GeneID:5607"
                     /db_xref="HGNC:HGNC:6845"
                     /db_xref="MIM:602520"
     exon            1..768
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     CDS             634..1980
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /EC_number="2.7.12.2"
                     /note="isoform A is encoded by transcript variant 1; dual
                     specificity mitogen-activated protein kinase kinase 5; MAP
                     kinase kinase MEK5b; MAPK/ERK kinase 5; MEK 5; MAPKK 5;
                     MAP kinase kinase 5"
                     /codon_start=1
                     /product="dual specificity mitogen-activated protein
                     kinase kinase 5 isoform A"
                     /protein_id="NP_660143.1"
                     /db_xref="CCDS:CCDS10224.1"
                     /db_xref="GeneID:5607"
                     /db_xref="HGNC:HGNC:6845"
                     /db_xref="MIM:602520"
                     /translation="MLWLALGPFPAMENQVLVIRIKIPNSGAVDWTVHSGPQLLFRDV
                     LDVIGQVLPEATTTAFEYEDEDGDRITVRSDEEMKAMLSYYYSTVMEQQVNGQLIEPL
                     QIFPRACKPPGERNIHGLKVNTRAGPSQHSSPAVSDSLPSNSLKKSSAELKKILANGQ
                     MNEQDIRYRDTLGHGNGGTVYKAYHVPSGKILAVKVILLDITLELQKQIMSELEILYK
                     CDSSYIIGFYGAFFVENRISICTEFMDGGSLDVYRKMPEHVLGRIAVAVVKGLTYLWS
                     LKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLVNSIAKTYVGTNAYMAPERISGEQYG
                     IHSDVWSLGISFMELALGRFPYPQIQKNQGSLMPLQLLQCIVDEDSPVLPVGEFSEPF
                     VHFITQCMRKQPKERPAPEELMGHPFIVQFNDGNAAVVSMWVCRALEERRSQQGPP"
     exon            769..817
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            818..885
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            886..955
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            956..996
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            997..1064
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1065..1113
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1114..1178
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1179..1218
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1219..1287
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1288..1369
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1370..1431
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1432..1480
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1481..1554
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1555..1605
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1606..1677
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1678..1707
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1708..1734
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1735..1767
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1768..1829
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1830..1875
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     exon            1876..2344
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2319..2324
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /note="hexamer: AATAAA"
     polyA_site      2344
                     /gene="MAP2K5"
                     /gene_synonym="HsT17454; MAPKK5; MEK5; PRKMK5"
                     /note="major polyA site"
ORIGIN      
        1 gccttcctcc tcctcctctc gccgctaccg ccgtcgccgc cgccgcagcc gccgccagtc
       61 cgcgcggcct cgggtggccg gagctcagcc tgcgcgcgcc gcgccctgtg tctccgggtg
      121 gggcagaaga ctcgcccctt gaacctcccg cggggactct ccgtggtgtg gcggccctgg
      181 ggctctttct taatagcccc ggactgagtc ccctccagtc gaggaccctc tcctagtcca
      241 ctgacgagcg gtggacacct gccgctgtat ctcccccaaa ccgagtcctt gccctgctgc
      301 ctcctcatac ccacacggcg gcagagacct tcaccatagc gttcgctcaa ctccagaacc
      361 ttccgacctc cgctagttcc tgcgggcctt tgcccgcttc ccggtgcacc ctccccggga
      421 gacacctcag acccccgaca gcctgggcag gctcggtgcc tgcgggtgcg ttcctgatca
      481 cccctcccct cttccctccc cctcatcctc cattcccttg ttttcaccct ctgtcctctg
      541 cccgtcactc cccttgtcac ctcttggagc cccctcctaa ccagcggcca gtgggtttcc
      601 cataccccag gatgtgagcc tctttaacct gtaatgctgt ggctagccct tggccccttt
      661 cctgccatgg agaaccaggt gctggtaatt cgcatcaaga tcccaaatag tggcgcggtg
      721 gactggacag tgcactccgg gccgcagtta ctcttcaggg atgtgctgga tgtgataggc
      781 caggttctgc ctgaagcaac aactacagca tttgaatatg aagatgaaga tggtgatcga
      841 attacagtga gaagtgatga ggaaatgaag gcaatgctgt catattatta ttccacagta
      901 atggaacagc aagtaaatgg acagttaata gagcctctgc agatatttcc aagagcctgc
      961 aagcctcctg gggaacggaa catacatggc ctgaaggtga atactcgggc cggaccctct
     1021 caacacagca gcccagcagt ctcagattca cttccaagca atagcttaaa gaagtcttct
     1081 gctgaactga aaaaaatact agccaatggc cagatgaatg aacaagacat acgatatcgg
     1141 gacactcttg gtcatggcaa cggaggcaca gtctacaaag catatcatgt cccgagtggg
     1201 aaaatattag ctgtaaaggt catactacta gatattacac tggaacttca gaagcaaatt
     1261 atgtctgaat tggaaattct ttataagtgc gattcatcat atatcattgg attttatgga
     1321 gcattttttg tagaaaacag gatttcaata tgtacagaat tcatggatgg gggatctttg
     1381 gatgtatata ggaaaatgcc agaacatgtc cttggaagaa ttgcagtagc agttgttaaa
     1441 ggccttactt atttgtggag tttaaagatt ttacatagag acgtgaagcc ctccaatatg
     1501 ctagtaaaca caagaggaca ggttaagctg tgtgattttg gagttagcac tcagctggtg
     1561 aattctatag ccaagacgta tgttggaaca aatgcttata tggcgcctga aaggatttca
     1621 ggggagcagt atggaattca ttctgatgtc tggagcttag gaatctcttt tatggagctt
     1681 gctcttggga ggtttccata tcctcagatt cagaaaaacc agggatcttt aatgcctctc
     1741 cagcttctgc agtgcattgt tgatgaggat tcgcccgtcc ttccagttgg agagttctcg
     1801 gagccatttg tacatttcat cactcagtgt atgcgaaaac agccaaaaga aaggccagca
     1861 cctgaagaat tgatgggcca cccgttcatc gtgcagttca atgatggaaa tgccgccgtg
     1921 gtgtccatgt gggtgtgccg ggcgctggag gagaggcgga gccagcaggg gcccccgtga
     1981 ggctgccgca gggcactgaa agcccaggac cagtaaccaa ggagaacaac ccacccgtcg
     2041 cccttctccg tatgctgcct gcgccagaag agctttgctg ggccctggct tccctgccct
     2101 cgccttcacc tctgtcagca ggtggccttg cctggggagc cccatgtgtg gcccacccca
     2161 ccaggccatc cccatacctt ctggtttgaa ggcgctgaca ctggcagaga ggtaaagggt
     2221 ggggcattga gaatggaggc tcccagggtc cctgcccact tctgttttcc taatgttttt
     2281 ctctataaag ggtcaggccc gtcagcatca ctgatgggaa taaaagtatt aatgctttgt
     2341 gaca
//
