LOCUS       NM_145109               2256 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase 3 (MAP2K3),
            transcript variant B, mRNA.
ACCESSION   NM_145109 XM_001130488
VERSION     NM_145109.3
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 2256)
  AUTHORS   Pranteda,A., Piastra,V., Serra,M., Bernardini,R., Lo Sardo,F.,
            Carpano,S., Diodoro,M.G., Bartolazzi,A., Milella,M., Blandino,G.
            and Bossi,G.
  TITLE     Activated MKK3/MYC crosstalk impairs dabrafenib response in
            BRAFV600E colorectal cancer leading to resistance
  JOURNAL   Biomed Pharmacother 167, 115480 (2023)
   PUBMED   37713993
  REMARK    GeneRIF: Activated MKK3/MYC crosstalk impairs dabrafenib response
            in BRAFV600E colorectal cancer leading to resistance.
REFERENCE   2  (bases 1 to 2256)
  AUTHORS   Gu,L., Li,Z., Zhang,X., Chen,M. and Zhang,X.
  TITLE     Identification of MAP Kinase Kinase 3 as a protein target of
            myricetin in non-small cell lung cancer cells
  JOURNAL   Biomed Pharmacother 161, 114460 (2023)
   PUBMED   36870282
  REMARK    GeneRIF: Identification of MAP Kinase Kinase 3 as a protein target
            of myricetin in non-small cell lung cancer cells.
REFERENCE   3  (bases 1 to 2256)
  AUTHORS   Ayala-Marin,Y.M., Grant,A.H., Rodriguez,G. and Kirken,R.A.
  TITLE     Quadruple and Truncated MEK3 Mutants Identified from Acute
            Lymphoblastic Leukemia Promote Degradation and Enhance
            Proliferation
  JOURNAL   Int J Mol Sci 22 (22), 12210 (2021)
   PUBMED   34830095
  REMARK    GeneRIF: Quadruple and Truncated MEK3 Mutants Identified from Acute
            Lymphoblastic Leukemia Promote Degradation and Enhance
            Proliferation.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2256)
  AUTHORS   Zhou,Y., Liu,J., Chu,L., Dong,M. and Feng,L.
  TITLE     Whole-Exome Sequencing Reveals Novel Variations in Patients with
            Familial Von Hippel-Lindau Syndrome
  JOURNAL   World Neurosurg 150, e696-e704 (2021)
   PUBMED   33774214
  REMARK    GeneRIF: Whole-Exome Sequencing Reveals Novel Variations in
            Patients with Familial Von Hippel-Lindau Syndrome.
REFERENCE   5  (bases 1 to 2256)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   6  (bases 1 to 2256)
  AUTHORS   Stein,B., Brady,H., Yang,M.X., Young,D.B. and Barbosa,M.S.
  TITLE     Cloning and characterization of MEK6, a novel member of the
            mitogen-activated protein kinase kinase cascade
  JOURNAL   J Biol Chem 271 (19), 11427-11433 (1996)
   PUBMED   8626699
REFERENCE   7  (bases 1 to 2256)
  AUTHORS   Raingeaud,J., Whitmarsh,A.J., Barrett,T., Derijard,B. and
            Davis,R.J.
  TITLE     MKK3- and MKK6-regulated gene expression is mediated by the p38
            mitogen-activated protein kinase signal transduction pathway
  JOURNAL   Mol Cell Biol 16 (3), 1247-1255 (1996)
   PUBMED   8622669
REFERENCE   8  (bases 1 to 2256)
  AUTHORS   Doza,Y.N., Cuenda,A., Thomas,G.M., Cohen,P. and Nebreda,A.R.
  TITLE     Activation of the MAP kinase homologue RK requires the
            phosphorylation of Thr-180 and Tyr-182 and both residues are
            phosphorylated in chemically stressed KB cells
  JOURNAL   FEBS Lett 364 (2), 223-228 (1995)
   PUBMED   7750576
REFERENCE   9  (bases 1 to 2256)
  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 2256)
  AUTHORS   Zheng,C.F. and Guan,K.L.
  TITLE     Properties of MEKs, the kinases that phosphorylate and activate the
            extracellular signal-regulated kinases
  JOURNAL   J Biol Chem 268 (32), 23933-23939 (1993)
   PUBMED   8226933
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA131175.1, BC032478.1,
            D87116.1 and AI758302.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_145109.2.
            
            Summary: The protein encoded by this gene is a dual specificity
            protein kinase that belongs to the MAP kinase kinase family. This
            kinase is activated by mitogenic and environmental stress, and
            participates in the MAP kinase-mediated signaling cascade. It
            phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can
            be activated by insulin, and is necessary for the expression of
            glucose transporter. Expression of RAS oncogene is found to result
            in the accumulation of the active form of this kinase, which thus
            leads to the constitutive activation of MAPK14, and confers
            oncogenic transformation of primary cells. The inhibition of this
            kinase is involved in the pathogenesis of Yersina
            pseudotuberculosis. Multiple alternatively spliced transcript
            variants that encode distinct isoforms have been reported for this
            gene. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (B) encodes the longer isoform
            (B).
            
            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 :: SRR7346977.1309238.1,
                                           SRR1660809.88144.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000342679.9/ ENSP00000345083.4
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-10                DA131175.1         56-65
            11-259              BC032478.1         1-249
            260-2021            D87116.1           107-1868
            2022-2256           AI758302.1         9-243               c
FEATURES             Location/Qualifiers
     source          1..2256
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17p11.2"
     gene            1..2256
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /note="mitogen-activated protein kinase kinase 3"
                     /db_xref="GeneID:5606"
                     /db_xref="HGNC:HGNC:6843"
                     /db_xref="MIM:602315"
     exon            1..259
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     CDS             211..1254
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /EC_number="2.7.12.2"
                     /note="isoform B is encoded by transcript variant B;
                     MAPK/ERK kinase 3; MAP kinase kinase 3; dual specificity
                     mitogen-activated protein kinase kinase 3; SAPK kinase 2;
                     stress-activated protein kinase kinase 2; MEK 3; MAPKK 3"
                     /codon_start=1
                     /product="dual specificity mitogen-activated protein
                     kinase kinase 3 isoform B"
                     /protein_id="NP_659731.1"
                     /db_xref="CCDS:CCDS11217.1"
                     /db_xref="GeneID:5606"
                     /db_xref="HGNC:HGNC:6843"
                     /db_xref="MIM:602315"
                     /translation="MESPASSQPASMPQSKGKSKRKKDLRISCMSKPPAPNPTPPRNL
                     DSRTFITIGDRNFEVEADDLVTISELGRGAYGVVEKVRHAQSGTIMAVKRIRATVNSQ
                     EQKRLLMDLDINMRTVDCFYTVTFYGALFREGDVWICMELMDTSLDKFYRKVLDKNMT
                     IPEDILGEIAVSIVRALEHLHSKLSVIHRDVKPSNVLINKEGHVKMCDFGISGYLVDS
                     VAKTMDAGCKPYMAPERINPELNQKGYNVKSDVWSLGITMIEMAILRFPYESWGTPFQ
                     QLKQVVEEPSPQLPADRFSPEFVDFTAQCLRKNPAERMSYLELMEHPFFTLHKTKKTD
                     IAAFVKEILGEDS"
     exon            260..326
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            327..375
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            376..489
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            490..609
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            610..726
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            727..778
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            779..906
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            907..984
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            985..1124
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            1125..1170
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     exon            1171..2256
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2154..2159
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /note="hexamer: AATATA"
     polyA_site      2173
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /note="major polyA site"
ORIGIN      
        1 agtctgtctc cggcgccgcc cgtcgcggac tcgtccttgc tgcagtcgcc gccgcagtcc
       61 tcgccgcagt cgccgccgcc gccgccgccg ccgccgctgc tcctccgcct ggcctgggcc
      121 gtctgcccgc agccatgagc gtgctcggcc ccggtggagc ccgcagtcct ctagattagt
      181 ctccaccgcc gtccaggacc cacttgcagc atggagtcgc ccgcctcgag ccagcccgcc
      241 agcatgcccc agtccaaagg aaaatccaag aggaagaagg atctacggat atcctgcatg
      301 tccaagccac ccgcacccaa ccccacaccc ccccggaacc tggactcccg gaccttcatc
      361 accattggag acagaaactt tgaggtggag gctgatgact tggtgaccat ctcagaactg
      421 ggccgtggag cctatggggt ggtagagaag gtgcggcacg cccagagcgg caccatcatg
      481 gccgtgaagc ggatccgggc caccgtgaac tcacaggagc agaagcggct gctcatggac
      541 ctggacatca acatgcgcac ggtcgactgt ttctacactg tcaccttcta cggggcacta
      601 ttcagagagg gagacgtgtg gatctgcatg gagctcatgg acacatcctt ggacaagttc
      661 taccggaagg tgctggataa aaacatgaca attccagagg acatccttgg ggagattgct
      721 gtgtctatcg tgcgggccct ggagcatctg cacagcaagc tgtcggtgat ccacagagat
      781 gtgaagccct ccaatgtcct tatcaacaag gagggccatg tgaagatgtg tgactttggc
      841 atcagtggct acttggtgga ctctgtggcc aagacgatgg atgccggctg caagccctac
      901 atggcccctg agaggatcaa cccagagctg aaccagaagg gctacaatgt caagtccgac
      961 gtctggagcc tgggcatcac catgattgag atggccatcc tgcggttccc ttacgagtcc
     1021 tgggggaccc cgttccagca gctgaagcag gtggtggagg agccgtcccc ccagctccca
     1081 gccgaccgtt tctcccccga gtttgtggac ttcactgctc agtgcctgag gaagaacccc
     1141 gcagagcgta tgagctacct ggagctgatg gagcacccct tcttcacctt gcacaaaacc
     1201 aagaagacgg acattgctgc cttcgtgaag gagatcctgg gagaagactc ataggggctg
     1261 ggcctcggac cccactccgg ccctccagag ccccacagcc ccatctgcgg gggcagtgct
     1321 cacccacacc ataagctact gccatcctgg cccagggcat ctgggaggaa ccgagggggc
     1381 tgctcccacc tggctctgtg gcgagccatt tgtcccaagt gccaaagaag cagaccattg
     1441 gggctcccag ccaggccctt gtcggcccca ccagtgcctc tccctgctgc tcctaggacc
     1501 cgtctccagc tgctgagatc ctggactgag ggggcctgga tgccccctgt ggatgctgct
     1561 gcccctgcac agcaggctgc cagtgcctgg gtggatgggc caccgccttg cccagcctgg
     1621 atgccatcca agttgtatat ttttttaatc tctcgactga atggactttg cacactttgg
     1681 cccagggtgg ccacacctct atcccggctt tggtgcgggg tacacaagag gggatgagtt
     1741 gtgtgaatac cccaagactc ccatgaggga gatgccatga gccgcccaag gccttcccct
     1801 ggcactggca aacagggcct ctgcggagca cactggctca cccagtcctg cccgccaccg
     1861 ttatcggtgt cattcacctt tcgtgttttt tttaatttat cctctgttga ttttttcttt
     1921 tgctttatgg gtttggcttg tttttcttgc atggtttgga gctgatcgct tctcccccac
     1981 cccctagggt accagcaggc agagccttgc cctctgctca ggctggggtc cagtgggagg
     2041 ggcccaagat ctctgctcag agaagtgcag ggggagcctt ccagctcact ctccctgagg
     2101 actggcttga caggggctat gggtttgctt tggtgttgtt tttaaaaaaa gaaaatatat
     2161 ttttttgaaa aaacgactgc ccatcccggg tcctttccct gatgggttgg ggcagttacc
     2221 tggttgctgt tttaattaaa aaaaaaaaaa aaaaaa
//
