LOCUS       NM_002755               2547 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase 1 (MAP2K1),
            transcript variant 1, mRNA.
ACCESSION   NM_002755
VERSION     NM_002755.4
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 2547)
  AUTHORS   Alomari,A.K., Harms,P.W., Andea,A.A. and Warren,S.J.
  TITLE     MAP2K1-mutated melanocytic tumors have reproducible histopathologic
            features and share similarities with melanocytic tumors with BRAF
            V600E mutations
  JOURNAL   J Cutan Pathol 50 (12), 1083-1093 (2023)
   PUBMED   37565534
  REMARK    GeneRIF: MAP2K1-mutated melanocytic tumors have reproducible
            histopathologic features and share similarities with melanocytic
            tumors with BRAF V600E mutations.
            Review article
REFERENCE   2  (bases 1 to 2547)
  AUTHORS   Patil,K., Wang,Y., Chen,Z., Suresh,K. and Radhakrishnan,R.
  TITLE     Activating mutations drive human MEK1 kinase using a gear-shifting
            mechanism
  JOURNAL   Biochem J 480 (21), 1733-1751 (2023)
   PUBMED   37869794
  REMARK    GeneRIF: Activating mutations drive human MEK1 kinase using a
            gear-shifting mechanism.
REFERENCE   3  (bases 1 to 2547)
  AUTHORS   Kemps,P.G., van den Bos,C. and van Halteren,A.G.S.
  CONSRTM   International Study Group
  TITLE     Clinical associations of BRAF and MAP2K1 mutations in pediatric
            Langerhans cell histiocytosis: When 1 + 1 = 3
  JOURNAL   Am J Hematol 98 (9), E244-E246 (2023)
   PUBMED   37357851
  REMARK    GeneRIF: Clinical associations of BRAF and MAP2K1 mutations in
            pediatric Langerhans cell histiocytosis: When 1 + 1 = 3.
REFERENCE   4  (bases 1 to 2547)
  AUTHORS   Andrianova,E.P., Marmion,R.A., Shvartsman,S.Y. and Zhulin,I.B.
  TITLE     Evolutionary history of MEK1 illuminates the nature of deleterious
            mutations
  JOURNAL   Proc Natl Acad Sci U S A 120 (34), e2304184120 (2023)
   PUBMED   37579140
  REMARK    GeneRIF: Evolutionary history of MEK1 illuminates the nature of
            deleterious mutations.
REFERENCE   5  (bases 1 to 2547)
  AUTHORS   Xu,S., Robbins,D., Frost,J., Dang,A., Lange-Carter,C. and Cobb,M.H.
  TITLE     MEKK1 phosphorylates MEK1 and MEK2 but does not cause activation of
            mitogen-activated protein kinase
  JOURNAL   Proc Natl Acad Sci U S A 92 (15), 6808-6812 (1995)
   PUBMED   7624324
REFERENCE   6  (bases 1 to 2547)
  AUTHORS   Seger,R. and Krebs,E.G.
  TITLE     The MAPK signaling cascade
  JOURNAL   FASEB J 9 (9), 726-735 (1995)
   PUBMED   7601337
  REMARK    Review article
REFERENCE   7  (bases 1 to 2547)
  AUTHORS   Gelb,B.D. and Tartaglia,M.
  TITLE     Noonan Syndrome with Multiple Lentigines
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301557
REFERENCE   8  (bases 1 to 2547)
  AUTHORS   Rauen,K.A.
  TITLE     Cardiofaciocutaneous Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301365
REFERENCE   9  (bases 1 to 2547)
  AUTHORS   Roberts,A.E.
  TITLE     Noonan Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301303
REFERENCE   10 (bases 1 to 2547)
  AUTHORS   Seger,R., Seger,D., Lozeman,F.J., Ahn,N.G., Graves,L.M.,
            Campbell,J.S., Ericsson,L., Harrylock,M., Jensen,A.M. and
            Krebs,E.G.
  TITLE     Human T-cell mitogen-activated protein kinase kinases are related
            to yeast signal transduction kinases
  JOURNAL   J Biol Chem 267 (36), 25628-25631 (1992)
   PUBMED   1281467
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK291500.1, AK312356.1,
            L11284.1, BG709050.1 and CA419665.1.
            
            On Nov 22, 2019 this sequence version replaced NM_002755.3.
            
            Summary: The protein encoded by this gene is a member of the dual
            specificity protein kinase family, which acts as a
            mitogen-activated protein (MAP) kinase kinase. MAP kinases, also
            known as extracellular signal-regulated kinases (ERKs), act as an
            integration point for multiple biochemical signals. This protein
            kinase lies upstream of MAP kinases and stimulates the enzymatic
            activity of MAP kinases upon wide variety of extra- and
            intracellular signals. As an essential component of MAP kinase
            signal transduction pathway, this kinase is involved in many
            cellular processes such as proliferation, differentiation,
            transcription regulation and development. [provided by RefSeq, Jul
            2008].
            
            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 :: AK291500.1, L11284.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000307102.10/ ENSP00000302486.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-351               AK291500.1         1-351
            352-568             AK312356.1         298-514
            569-1905            AK291500.1         569-1905
            1906-1977           L11284.1           1543-1614
            1978-2538           BG709050.1         47-607
            2539-2547           CA419665.1         18-26               c
FEATURES             Location/Qualifiers
     source          1..2547
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="15"
                     /map="15q22.31"
     gene            1..2547
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /note="mitogen-activated protein kinase kinase 1"
                     /db_xref="GeneID:5604"
                     /db_xref="HGNC:HGNC:6840"
                     /db_xref="MIM:176872"
     exon            1..516
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     CDS             437..1618
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /EC_number="2.7.12.2"
                     /note="isoform 1 is encoded by transcript variant 1;
                     protein kinase, mitogen-activated, kinase 1 (MAP kinase
                     kinase 1); dual specificity mitogen-activated protein
                     kinase kinase 1; MEK 1; MAPKK 1; MAPK/ERK kinase 1; ERK
                     activator kinase 1"
                     /codon_start=1
                     /product="dual specificity mitogen-activated protein
                     kinase kinase 1 isoform 1"
                     /protein_id="NP_002746.1"
                     /db_xref="CCDS:CCDS10216.1"
                     /db_xref="GeneID:5604"
                     /db_xref="HGNC:HGNC:6840"
                     /db_xref="MIM:176872"
                     /translation="MPKKKPTPIQLNPAPDGSAVNGTSSAETNLEALQKKLEELELDE
                     QQRKRLEAFLTQKQKVGELKDDDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLE
                     IKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKAGR
                     IPEQILGKVSIAVIKGLTYLREKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDS
                     MANSFVGTRSYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELELMFG
                     CQVEGDAAETPPRPRTPGRPLSSYGMDSRPPMAIFELLDYIVNEPPPKLPSGVFSLEF
                     QDFVNKCLIKNPAERADLKQLMVHAFIKRSDAEEVDFAGWLCSTIGLNQPSTPTHAAG
                     V"
     exon            517..727
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            728..874
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            875..952
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            953..1004
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1005..1129
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1130..1331
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1332..1396
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1397..1458
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1459..1504
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     exon            1505..2547
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1886..1891
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /note="hexamer: ATTACA"
     polyA_site      1907
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /note="major polyA site"
     regulatory      2370..2375
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
                     /note="hexamer: ATTAAA"
     polyA_site      2399
                     /gene="MAP2K1"
                     /gene_synonym="CFC3; MAPKK1; MEK1; MEL; MKK1; PRKMK1"
ORIGIN      
        1 agtccctccc agggccgctt cgcagagcgg ctaggagcac ggcggcggcg gcactttccc
       61 cggcaggagc tggagctggg ctctggtgcg cgcgcggctg tgccgcccga gccggaggga
      121 ctggttggtt gagagagaga gaggaaggga atcccgggct gccgaaccgc acgttcagcc
      181 cgctccgctc ctgcagggca gcctttcggc tctctgcgcg cgaagccgag tcccgggcgg
      241 gtggggcggg ggtccactga gaccgctacc ggcccctcgg cgctgacggg accgcgcggg
      301 gcgcacccgc tgaaggcagc cccggggccc gcggcccgga cttggtcctg cgcagcgggc
      361 gcggggcagc gcagcgggag gaagcgagag gtgctgccct ccccccggag ttggaagcgc
      421 gttacccggg tccaaaatgc ccaagaagaa gccgacgccc atccagctga acccggcccc
      481 cgacggctct gcagttaacg ggaccagctc tgcggagacc aacttggagg ccttgcagaa
      541 gaagctggag gagctagagc ttgatgagca gcagcgaaag cgccttgagg cctttcttac
      601 ccagaagcag aaggtgggag aactgaagga tgacgacttt gagaagatca gtgagctggg
      661 ggctggcaat ggcggtgtgg tgttcaaggt ctcccacaag ccttctggcc tggtcatggc
      721 cagaaagcta attcatctgg agatcaaacc cgcaatccgg aaccagatca taagggagct
      781 gcaggttctg catgagtgca actctccgta catcgtgggc ttctatggtg cgttctacag
      841 cgatggcgag atcagtatct gcatggagca catggatgga ggttctctgg atcaagtcct
      901 gaagaaagct ggaagaattc ctgaacaaat tttaggaaaa gttagcattg ctgtaataaa
      961 aggcctgaca tatctgaggg agaagcacaa gatcatgcac agagatgtca agccctccaa
     1021 catcctagtc aactcccgtg gggagatcaa gctctgtgac tttggggtca gcgggcagct
     1081 catcgactcc atggccaact ccttcgtggg cacaaggtcc tacatgtcgc cagaaagact
     1141 ccaggggact cattactctg tgcagtcaga catctggagc atgggactgt ctctggtaga
     1201 gatggcggtt gggaggtatc ccatccctcc tccagatgcc aaggagctgg agctgatgtt
     1261 tgggtgccag gtggaaggag atgcggctga gaccccaccc aggccaagga cccccgggag
     1321 gccccttagc tcatacggaa tggacagccg acctcccatg gcaatttttg agttgttgga
     1381 ttacatagtc aacgagcctc ctccaaaact gcccagtgga gtgttcagtc tggaatttca
     1441 agattttgtg aataaatgct taataaaaaa ccccgcagag agagcagatt tgaagcaact
     1501 catggttcat gcttttatca agagatctga tgctgaggaa gtggattttg caggttggct
     1561 ctgctccacc atcggcctta accagcccag cacaccaacc catgctgctg gcgtctaagt
     1621 gtttgggaag caacaaagag cgagtcccct gcccggtggt ttgccatgtc gcttttgggc
     1681 ctccttccca tgcctgtctc tgttcagatg tgcatttcac ctgtgacaaa ggatgaagaa
     1741 cacagcatgt gccaagattc tactcttgtc atttttaata ttactgtctt tattcttatt
     1801 actattattg ttcccctaag tggattggct ttgtgcttgg ggctatttgt gtgtatgctg
     1861 atgatcaaaa cctgtgccag gctgaattac agtgaaattt tggtgaatgt gggtagtcat
     1921 tcttacaatt gcactgctgt tcctgctcca tgactggctg tctgcctgta ttttcgggat
     1981 tctttgacat ttggtggtac tttattcttg ctgggcatac tttctctcta ggagggagcc
     2041 ttgtgagatc cttcacaggc agtgcatgtg aagcatgctt tgctgctatg aaaatgagca
     2101 tcagagagtg tacatcatgt tattttatta ttattatttg cttttcatgt agaactcagc
     2161 agttgacatc caaatctagc cagagccctt cactgccatg atagctgggg cttcaccagt
     2221 ctgtctactg tggtgatctg tagacttctg gttgtatttc tatatttatt ttcagtatac
     2281 tgtgtgggat acttagtggt atgtctcttt aagttttgat taatgtttct taaatggaat
     2341 tattttgaat gtcacaaatt gatcaagata ttaaaatgtc ggatttatct ttccccatat
     2401 ccaagtacca atgctgttgt aaacaacgtg tatagtgcct aaaattgtat gaaaatcctt
     2461 ttaaccattt taacctagat gtttaacaaa tctaatctct tattctaata aatatactat
     2521 gaaataaaaa aaaaaggatg aaagcta
//
