LOCUS       NM_002401               4752 bp    mRNA    linear   PRI 09-DEC-2024
DEFINITION  Homo sapiens mitogen-activated protein kinase kinase kinase 3
            (MAP3K3), transcript variant 2, mRNA.
ACCESSION   NM_002401
VERSION     NM_002401.5
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 4752)
  AUTHORS   Zhang,B., He,R., Xu,Z., Sun,Y., Wei,L., Li,L., Liu,Y., Guo,W.,
            Song,L., Wang,H., Lin,Z. and Ma,L.
  TITLE     Somatic mutation spectrum of a Chinese cohort of pediatrics with
            vascular malformations
  JOURNAL   Orphanet J Rare Dis 18 (1), 261 (2023)
   PUBMED   37658401
  REMARK    GeneRIF: Somatic mutation spectrum of a Chinese cohort of
            pediatrics with vascular malformations.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4752)
  AUTHORS   Segal,D., Maier,S., Mastromarco,G.J., Qian,W.W., Nabeel-Shah,S.,
            Lee,H., Moore,G., Lacoste,J., Larsen,B., Lin,Z.Y.,
            Selvabaskaran,A., Liu,K., Smibert,C., Zhang,Z., Greenblatt,J.,
            Peng,J., Lee,H.O., Gingras,A.C. and Taipale,M.
  TITLE     A central chaperone-like role for 14-3-3 proteins in human cells
  JOURNAL   Mol Cell 83 (6), 974-993 (2023)
   PUBMED   36931259
REFERENCE   3  (bases 1 to 4752)
  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 4752)
  AUTHORS   Yang,C., Shi,J., Wang,J., Hao,D., An,J. and Jiang,J.
  TITLE     Circ_0006988 promotes the proliferation, metastasis and
            angiogenesis of non-small cell lung cancer cells by modulating
            miR-491-5p/MAP3K3 axis
  JOURNAL   Cell Cycle 20 (13), 1334-1346 (2021)
   PUBMED   34189997
  REMARK    GeneRIF: Circ_0006988 promotes the proliferation, metastasis and
            angiogenesis of non-small cell lung cancer cells by modulating
            miR-491-5p/MAP3K3 axis.
REFERENCE   5  (bases 1 to 4752)
  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 4752)
  AUTHORS   Sun,W., Kesavan,K., Schaefer,B.C., Garrington,T.P., Ware,M.,
            Johnson,N.L., Gelfand,E.W. and Johnson,G.L.
  TITLE     MEKK2 associates with the adapter protein Lad/RIBP and regulates
            the MEK5-BMK1/ERK5 pathway
  JOURNAL   J Biol Chem 276 (7), 5093-5100 (2001)
   PUBMED   11073940
REFERENCE   7  (bases 1 to 4752)
  AUTHORS   Yang,J., Boerm,M., McCarty,M., Bucana,C., Fidler,I.J., Zhuang,Y.
            and Su,B.
  TITLE     Mekk3 is essential for early embryonic cardiovascular development
  JOURNAL   Nat Genet 24 (3), 309-313 (2000)
   PUBMED   10700190
REFERENCE   8  (bases 1 to 4752)
  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   9  (bases 1 to 4752)
  AUTHORS   Fanger,G.R., Widmann,C., Porter,A.C., Sather,S., Johnson,G.L. and
            Vaillancourt,R.R.
  TITLE     14-3-3 proteins interact with specific MEK kinases
  JOURNAL   J Biol Chem 273 (6), 3476-3483 (1998)
   PUBMED   9452471
REFERENCE   10 (bases 1 to 4752)
  AUTHORS   Ellinger-Ziegelbauer,H., Brown,K., Kelly,K. and Siebenlist,U.
  TITLE     Direct activation of the stress-activated protein kinase (SAPK) and
            extracellular signal-regulated protein kinase (ERK) pathways by an
            inducible mitogen-activated protein Kinase/ERK kinase kinase 3
            (MEKK) derivative
  JOURNAL   J Biol Chem 272 (5), 2668-2674 (1997)
   PUBMED   9006902
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC046185.14, BQ643432.1,
            AL834303.1, BM728104.1, BM800091.1 and BU633068.1.
            
            On Jun 2, 2019 this sequence version replaced NM_002401.4.
            
            Summary: This gene product is a 626-amino acid polypeptide that is
            96.5% identical to mouse Mekk3. Its catalytic domain is closely
            related to those of several other kinases, including mouse Mekk2,
            tobacco NPK, and yeast Ste11. Northern blot analysis revealed a
            4.6-kb transcript that appears to be ubiquitously expressed. This
            protein directly regulates the stress-activated protein kinase
            (SAPK) and extracellular signal-regulated protein kinase (ERK)
            pathways by activating SEK and MEK1/2 respectively; it does not
            regulate the p38 pathway. In cotransfection assays, it enhanced
            transcription from a nuclear factor kappa-B (NFKB)-dependent
            reporter gene, consistent with a role in the SAPK pathway.
            Alternatively spliced transcript variants encoding distinct
            isoforms have been observed. [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 :: BC090859.1, U78876.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000361733.8/ ENSP00000354485.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-24                AC046185.14        107183-107206       c
            25-602              BQ643432.1         2-579
            603-3534            AL834303.1         671-3602
            3535-4073           BM728104.1         58-596
            4074-4518           BM800091.1         284-728
            4519-4752           BU633068.1         23-256              c
FEATURES             Location/Qualifiers
     source          1..4752
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q23.3"
     gene            1..4752
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /note="mitogen-activated protein kinase kinase kinase 3"
                     /db_xref="GeneID:4215"
                     /db_xref="HGNC:HGNC:6855"
                     /db_xref="MIM:602539"
     exon            1..347
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     CDS             344..2224
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /EC_number="2.7.11.25"
                     /note="isoform 2 is encoded by transcript variant 2;
                     MAP/ERK kinase kinase 3; MAPK/ERK kinase kinase 3; MEKK 3;
                     MEK kinase 3"
                     /codon_start=1
                     /product="mitogen-activated protein kinase kinase kinase 3
                     isoform 2"
                     /protein_id="NP_002392.2"
                     /db_xref="CCDS:CCDS32702.1"
                     /db_xref="GeneID:4215"
                     /db_xref="HGNC:HGNC:6855"
                     /db_xref="MIM:602539"
                     /translation="MDEQEALNSIMNDLVALQMNRRHRMPGYETMKNKDTGHSNRQSD
                     VRIKFEHNGERRIIAFSRPVKYEDVEHKVTTVFGQPLDLHYMNNELSILLKNQDDLDK
                     AIDILDRSSSMKSLRILLLSQDRNHNSSSPHSGVSRQVRIKASQSAGDINTIYQPPEP
                     RSRHLSVSSQNPGRSSPPPGYVPERQQHIARQGSYTSINSEGEFIPETSEQCMLDPLS
                     SAENSLSGSCQSLDRSADSPSFRKSRMSRAQSFPDNRQEYSDRETQLYDKGVKGGTYP
                     RRYHVSVHHKDYSDGRRTFPRIRRHQGNLFTLVPSSRSLSTNGENMGLAVQYLDPRGR
                     LRSADSENALSVQERNVPTKSPSAPINWRRGKLLGQGAFGRVYLCYDVDTGRELASKQ
                     VQFDPDSPETSKEVSALECEIQLLKNLQHERIVQYYGCLRDRAEKTLTIFMEYMPGGS
                     VKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDF
                     GASKRLQTICMSGTGMRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPP
                     WAEYEAMAAIFKIATQPTNPQLPSHISEHGRDFLRRIFVEARQRPSAEELLTHHFAQL
                     MY"
     exon            348..469
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            470..510
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            511..610
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            611..724
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            725..845
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            846..979
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            980..1053
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            1054..1121
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            1122..1214
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            1215..1406
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            1407..1555
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            1556..1687
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            1688..1817
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            1818..1995
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     exon            1996..4752
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4733..4738
                     /regulatory_class="polyA_signal_sequence"
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /note="hexamer: AATAAA"
     polyA_site      4752
                     /gene="MAP3K3"
                     /gene_synonym="CCM5; MAPKKK3; MEKK3"
                     /note="major polyA site"
ORIGIN      
        1 gtttttcgga gcgttcctga ggtggagaac ggtggccgga cggagagact gcgggtctga
       61 gggactggcg ggcgggcggg ccgagcggcg ccgccgaggc cgggctgggc cgagcccagg
      121 agcgcccggg atgtagcggg ccaccctgcc gatgccacag cgcccggccg cgggcggagc
      181 cggagccgga gcctggggag gcggcggggg cccagagcgc agcccgcgcc ccccgcgcgg
      241 agccaggccc gctgccgtcc ccgccgcccg ggcccccggc atgcagcccc ggctgcggag
      301 gtgacactca cggaccttag ccaccgccgc cgccatcgcc accatggacg aacaggaggc
      361 attgaactca atcatgaacg atctggtggc cctccagatg aaccgacgtc accggatgcc
      421 tggatatgag accatgaaga acaaagacac aggtcactca aataggcaga gtgacgtcag
      481 aatcaagttc gagcacaacg gggagaggcg aattatagcg ttcagccggc ctgtgaaata
      541 tgaagatgtg gagcacaagg tgacaacagt atttggacaa cctcttgatc tacattacat
      601 gaacaatgag ctctccatcc tgctgaaaaa ccaagatgat cttgataaag caattgacat
      661 tttagataga agctcaagca tgaaaagcct taggatattg ctgttgtccc aggacagaaa
      721 ccataacagt tcctctcccc actctggggt gtccagacag gtgcggatca aggcttccca
      781 gtccgcaggg gatataaata ctatctacca gccccccgag cccagaagca ggcacctctc
      841 tgtcagctcc cagaaccctg gccgaagctc acctccccct ggctatgttc ctgagcggca
      901 gcagcacatt gcccggcagg ggtcctacac cagcatcaac agtgaggggg agttcatccc
      961 agagaccagc gagcagtgca tgctggatcc cctgagcagt gcagaaaatt ccttgtctgg
     1021 aagctgccaa tccttggaca ggtcagcaga cagcccatcc ttccggaaat cacgaatgtc
     1081 ccgtgcccag agcttccctg acaacagaca ggaatactca gatcgggaaa ctcagcttta
     1141 tgacaaaggg gtcaaaggtg gaacctaccc ccggcgctac cacgtgtctg tgcaccacaa
     1201 ggactacagt gatggcagaa gaacatttcc ccgaatacgg cgtcatcaag gcaacttgtt
     1261 caccctggtg ccctccagcc gctccctgag cacaaatggc gagaacatgg gtctggctgt
     1321 gcaatacctg gacccccgtg ggcgcctgcg gagtgcggac agcgagaatg ccctctctgt
     1381 gcaggagagg aatgtgccaa ccaagtctcc cagtgccccc atcaactggc gccggggaaa
     1441 gctcctgggc cagggtgcct tcggcagggt ctatttgtgc tatgacgtgg acacgggacg
     1501 tgaacttgct tccaagcagg tccaatttga tccagacagt cctgagacaa gcaaggaggt
     1561 gagtgctctg gagtgcgaga tccagttgct aaagaacttg cagcatgagc gcatcgtgca
     1621 gtactatggc tgtctgcggg accgcgctga gaagaccctg accatcttca tggagtacat
     1681 gccagggggc tcggtgaaag accagttgaa ggcttacggt gctctgacag agagcgtgac
     1741 ccgaaagtac acgcggcaga tcctggaggg catgtcctac ctgcacagca acatgattgt
     1801 tcaccgggac attaagggag ccaacatcct ccgagactct gctgggaatg taaagctggg
     1861 ggactttggg gccagcaaac gcctgcagac gatctgtatg tcggggacgg gcatgcgctc
     1921 cgtcactggc acaccctact ggatgagccc tgaggtgatc agcggcgagg gctatggaag
     1981 gaaagcagac gtgtggagcc tgggctgcac tgtggtggag atgctgacag agaaaccacc
     2041 gtgggcagag tatgaagcta tggccgccat cttcaagatt gccacccagc ccaccaatcc
     2101 tcagctgccc tcccacatct ctgaacatgg ccgggacttc ctgaggcgca tttttgtgga
     2161 ggctcgccag agaccttcag ctgaggagct gctcacacac cactttgcac agctcatgta
     2221 ctgagctctc acggccacac agctgccggt cgccctttgc tgcatggcag ggggctgctg
     2281 ctgggctcag tgaagttgct gcttctccca ggcaaggctg tggaccatgg agtggcagcc
     2341 cagccagcgt cggtctgtgc cccttccgcc actggggctc agagccgggg tggggtggct
     2401 gcagcctcag gactgggagc ccccagcctg tcagatccag gagctccagt gtcctgagct
     2461 cagcgtggag gggtaggggc tgggaacagt gtgcaaggca gccgtgggcc ccaccctcgg
     2521 ggatgtgtcc tgacactgca attggcaccg aagcccagag ggtctggggg cacaagactg
     2581 acgccagggt atgaagagtg ttattttcat tcaaagtgtt attttgtttt tccttccaat
     2641 gtctggagac caccagggca tctctgggct ggatgagctc ccacaagcct gagggaaagg
     2701 ccagcactcg ctagcagtgg caggcagagg cccaggctgc cgtcccctag agtcccaggt
     2761 tggctctgcc agtcctgtcc tttaccaaag atgaatgaag caaatgtcat gctgccttat
     2821 tcagggaagg aggagcctgt cctgcctgtg gccatgaccc tgcctctccc aggcaggggc
     2881 ccgcgatgtg gaactgctgc cactgagggg ggatccagtt ttgtcaatgc agttgtctct
     2941 gttttacaag ttggagtcac tcttatgctg tacccagttt ctaaactgga gactgtgtgt
     3001 gccctctggg ctctgagtac ccctgctttg ggcttgggcc taggctgcat tgaaaagagc
     3061 tgaaggttgt ggcctttgcg ctcctggccc agcctttgtt ccccactgga gcagaagggg
     3121 agatggacga cacggtcggg gcatctggcc tggccagtgc cctgatccca gagagcccga
     3181 ggaggtgtct caggctgcct gagtcgtgac ctgctaggcc agagcccact ccatctggta
     3241 gaagggaaag cccatatgct accaccagct gtgtccaaaa ccgccagctc tgttcttcct
     3301 cagccagcct cgcccatccc cttgaggtct cagccccttt cccttgtagc tcctcccctg
     3361 gagggggaat ggcagcaggg gttggggaaa cagcatctcc aagcagctta gagttggcca
     3421 tatttacctc agcctgggcg ctggtccttt cttccggccc ctcccctcca aaatgtgcct
     3481 attgctagag ctcctccctc tcaacaccca gtttccttgg gagttgtcat taaaggaaaa
     3541 aaaaaaaaaa aaaagccagt gcccagggat gggcatctcc agggagctgg ggattagtgc
     3601 caggcagccc tgccagccat gcctacatcc ccatgggcac agaacaagcc aaagccttcg
     3661 ttgtatgttg acgatgcact tttatgaatg tagtttctat cgctgttttt agccttttca
     3721 catcatgtaa tgtgaggcct tgtacttgtt aatttatatc tcagatcata tttgatggtt
     3781 tttatatata tcaattctag actgttacag gtgacggacg cctcaagaga gagaagagaa
     3841 aatgaaagca gctggttttg cagaagtgtg tgtcgcatgc gccagttggg cctggaccct
     3901 cctgtgtcca tccctgttcc cccaggggct ctatcagccc ctgtacccca cactgccctc
     3961 tgaagacaac acaggctcct gcttccacct cggcccttgc ccagggtggg gcctggccct
     4021 catcttgacc aaagctgctg tgtggcagct cggcctctct acgaccccat cttggtggct
     4081 gcacactctt cctggcccgc acccccatcc ccagtccctg ttccccaaga ggatacagag
     4141 cacggtgctg gctgactcaa ctgtgcgtcc caggttcagg gtcttacaga gctccacccc
     4201 ctggggtctt acctcactgg gaatgtgttt tgaaaatgaa tttgaagaca agccaacaaa
     4261 ccctgcactc caaaaaagca aaacagaccc taattttttt gtgccaaaaa ctgtggacat
     4321 gctggctcag catcctcagg accaagttgt tgcttaattt attgtttttt aataactaat
     4381 ccagataaaa agttgtgggg cttcagggtg acctgggccc aaaggttctg aagggcagtt
     4441 cctggcagcc ccaggcttgc tgtgggaagg ggccgtgccg tcactttctc atcattccat
     4501 ggggtgtgtc tgcctgggcc aactctgcat ggagaggcca gggctgggga cagtccgcac
     4561 tctgccaccc tcctgcccct tccacccacc ccagctctat gtctgtgtct gaattgtgga
     4621 tcgtgcagcc atggttattg tggaactgtg gaacctgcag ccatagttat ttgactatat
     4681 cttgaccgag ggcttgcagt gcaaagccag gccagtgttg cgcattactt acaataaaag
     4741 ggatcattta ta
//
