LOCUS       NP_659731                347 aa            linear   PRI 12-JUN-2025
DEFINITION  dual specificity mitogen-activated protein kinase kinase 3 isoform
            B [Homo sapiens].
ACCESSION   NP_659731 XP_001130488
VERSION     NP_659731.1
DBSOURCE    REFSEQ: accession 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  (residues 1 to 347)
  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  (residues 1 to 347)
  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  (residues 1 to 347)
  AUTHORS   Robinson,K.S., Toh,G.A., Rozario,P., Chua,R., Bauernfried,S.,
            Sun,Z., Firdaus,M.J., Bayat,S., Nadkarni,R., Poh,Z.S., Tham,K.C.,
            Harapas,C.R., Lim,C.K., Chu,W., Tay,C.W.S., Tan,K.Y., Zhao,T.,
            Bonnard,C., Sobota,R., Connolly,J.E., Common,J., Masters,S.L.,
            Chen,K.W., Ho,L., Wu,B., Hornung,V. and Zhong,F.L.
  TITLE     ZAKalpha-driven ribotoxic stress response activates the human NLRP1
            inflammasome
  JOURNAL   Science 377 (6603), 328-335 (2022)
   PUBMED   35857590
REFERENCE   4  (residues 1 to 347)
  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   5  (residues 1 to 347)
  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  (residues 1 to 347)
  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  (residues 1 to 347)
  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  (residues 1 to 347)
  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  (residues 1 to 347)
  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 (residues 1 to 347)
  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 Sep 20, 2006 this sequence version replaced XP_001130488.1.
            
            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##
FEATURES             Location/Qualifiers
     source          1..347
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17p11.2"
     Protein         1..347
                     /product="dual specificity mitogen-activated protein
                     kinase kinase 3 isoform B"
                     /EC_number="2.7.12.2"
                     /note="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"
                     /calculated_mol_wt=39187
     Region          1..46
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P46734.2)"
     Site            1
                     /site_type="acetylation"
                     /note="N-acetylmethionine.
                     /evidence=ECO:0007744|PubMed:19413330,
                     ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22814378;
                     propagated from UniProtKB/Swiss-Prot (P46734.2)"
     Site            3
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231; propagated from
                     UniProtKB/Swiss-Prot (P46734.2)"
     Site            15
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:20068231; propagated from
                     UniProtKB/Swiss-Prot (P46734.2)"
     Region          62..344
                     /region_name="PKc_MKK3_6"
                     /note="Catalytic domain of the dual-specificity Protein
                     Kinases, Mitogen-activated protein Kinase Kinases 3 and 6;
                     cd06617"
                     /db_xref="CDD:173729"
     Site            order(66,68,70..77,79,81,93..94,96..98,130,132..133,135,
                     137,142..146,153,194..195,197,207,212,215..218,343..344)
                     /site_type="other"
                     /note="dimer interface [polypeptide binding]"
                     /db_xref="CDD:173729"
     Site            order(70..74,78,91,93,124,140..143,145..146,149,190,
                     192..195,197,207..208,211,224..227,229,260,269)
                     /site_type="active"
                     /db_xref="CDD:173729"
     Site            order(70..74,76,78,91,93,124,140..143,145..146,148..149,
                     192,194..195,197,208)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:173729"
     Site            order(73..74,190,192..194,211,224..227,229,260,269)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:173729"
     Site            order(207..222,224..229)
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:173729"
     Site            218
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000269|PubMed:8622669; propagated from
                     UniProtKB/Swiss-Prot (P46734.2)"
     Site            222
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000269|PubMed:8622669; propagated from
                     UniProtKB/Swiss-Prot (P46734.2)"
     CDS             1..347
                     /gene="MAP2K3"
                     /gene_synonym="MAPKK3; MEK3; MKK3; PRKMK3; SAPKK-2;
                     SAPKK2"
                     /coded_by="NM_145109.3:211..1254"
                     /note="isoform B is encoded by transcript variant B"
                     /db_xref="CCDS:CCDS11217.1"
                     /db_xref="GeneID:5606"
                     /db_xref="HGNC:HGNC:6843"
                     /db_xref="MIM:602315"
ORIGIN      
        1 mespassqpa smpqskgksk rkkdlriscm skppapnptp prnldsrtfi tigdrnfeve
       61 addlvtisel grgaygvvek vrhaqsgtim avkriratvn sqeqkrllmd ldinmrtvdc
      121 fytvtfygal fregdvwicm elmdtsldkf yrkvldknmt ipedilgeia vsivralehl
      181 hsklsvihrd vkpsnvlink eghvkmcdfg isgylvdsva ktmdagckpy maperinpel
      241 nqkgynvksd vwslgitmie mailrfpyes wgtpfqqlkq vveepspqlp adrfspefvd
      301 ftaqclrknp aermsylelm ehpfftlhkt kktdiaafvk eilgeds
//
