LOCUS       NM_001270485            4905 bp    mRNA    linear   PRI 19-AUG-2024
DEFINITION  Homo sapiens calcium/calmodulin dependent protein kinase kinase 2
            (CAMKK2), transcript variant 8, mRNA.
ACCESSION   NM_001270485
VERSION     NM_001270485.2
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 4905)
  AUTHORS   Han,F., Wu,S., Dong,Y., Liu,Y., Sun,B. and Chen,L.
  TITLE     Aberrant expression of NEDD4L disrupts mitochondrial homeostasis by
            downregulating CaMKKbeta in diabetic kidney disease
  JOURNAL   J Transl Med 22 (1), 465 (2024)
   PUBMED   38755664
  REMARK    GeneRIF: Aberrant expression of NEDD4L disrupts mitochondrial
            homeostasis by downregulating CaMKKbeta in diabetic kidney disease.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 4905)
  AUTHORS   Wang,Y., Yang,C., Wen,J., Ju,L., Ren,Z., Zhang,T. and Liu,Y.
  TITLE     Whole-exome sequencing combined with postoperative data identify
            c.1614dup (CAMKK2) as a novel candidate monogenic obesity variant
  JOURNAL   Front Endocrinol (Lausanne) 15, 1334342 (2024)
   PUBMED   38469147
  REMARK    GeneRIF: Whole-exome sequencing combined with postoperative data
            identify c.1614dup (CAMKK2) as a novel candidate monogenic obesity
            variant.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 4905)
  AUTHORS   Kaiser,J., Nay,K., Horne,C.R., McAloon,L.M., Fuller,O.K.,
            Muller,A.G., Whyte,D.G., Means,A.R., Walder,K., Berk,M.,
            Hannan,A.J., Murphy,J.M., Febbraio,M.A., Gundlach,A.L. and
            Scott,J.W.
  TITLE     CaMKK2 as an emerging treatment target for bipolar disorder
  JOURNAL   Mol Psychiatry 28 (11), 4500-4511 (2023)
   PUBMED   37730845
  REMARK    GeneRIF: CaMKK2 as an emerging treatment target for bipolar
            disorder.
            Review article
REFERENCE   4  (bases 1 to 4905)
  AUTHORS   Mukherjee,D., Previs,R.A., Haines,C., Al Abo,M., Juras,P.K.,
            Strickland,K.C., Chakraborty,B., Artham,S., Whitaker,R.S.,
            Hebert,K., Fontenot,J., Patierno,S.R., Freedman,J.A., Lau,F.H.,
            Burow,M.E., Chang,C.Y. and McDonnell,D.P.
  TITLE     Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress
            Cancer Metastasis
  JOURNAL   Cancer Res 83 (17), 2889-2907 (2023)
   PUBMED   37335130
  REMARK    GeneRIF: Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to
            Suppress Cancer Metastasis.
REFERENCE   5  (bases 1 to 4905)
  AUTHORS   Gaff,J., Octaviana,F., Jackaman,C., Kamerman,P., Papadimitriou,J.,
            Lee,S., Mountford,J. and Price,P.
  TITLE     Expression in skin biopsies supports genetic evidence linking
            CAMKK2, P2X7R and P2X4R with HIV-associated sensory neuropathy
  JOURNAL   J Neurovirol 29 (3), 241-251 (2023)
   PUBMED   37166584
  REMARK    GeneRIF: Expression in skin biopsies supports genetic evidence
            linking CAMKK2, P2X7R and P2X4R with HIV-associated sensory
            neuropathy.
REFERENCE   6  (bases 1 to 4905)
  AUTHORS   Hawley,S.A., Pan,D.A., Mustard,K.J., Ross,L., Bain,J.,
            Edelman,A.M., Frenguelli,B.G. and Hardie,D.G.
  TITLE     Calmodulin-dependent protein kinase kinase-beta is an alternative
            upstream kinase for AMP-activated protein kinase
  JOURNAL   Cell Metab 2 (1), 9-19 (2005)
   PUBMED   16054095
  REMARK    GeneRIF: There is a significant basal activity and phosphorylation
            of AMPK in LKB1-deficient cells that can be stimulated by Ca2+
            ionophores, and studies using the CaMKK inhibitor STO-609 and
            isoform-specific siRNAs show that CaMKKbeta is required for this
            effect
REFERENCE   7  (bases 1 to 4905)
  AUTHORS   Ishikawa,Y., Tokumitsu,H., Inuzuka,H., Murata-Hori,M., Hosoya,H.
            and Kobayashi,R.
  TITLE     Identification and characterization of novel components of a
            Ca2+/calmodulin-dependent protein kinase cascade in HeLa cells
  JOURNAL   FEBS Lett 550 (1-3), 57-63 (2003)
   PUBMED   12935886
REFERENCE   8  (bases 1 to 4905)
  AUTHORS   Hsu,L.S., Chen,G.D., Lee,L.S., Chi,C.W., Cheng,J.F. and Chen,J.Y.
  TITLE     Human Ca2+/calmodulin-dependent protein kinase kinase beta gene
            encodes multiple isoforms that display distinct kinase activity
  JOURNAL   J Biol Chem 276 (33), 31113-31123 (2001)
   PUBMED   11395482
REFERENCE   9  (bases 1 to 4905)
  AUTHORS   Anderson,K.A., Means,R.L., Huang,Q.H., Kemp,B.E., Goldstein,E.G.,
            Selbert,M.A., Edelman,A.M., Fremeau,R.T. and Means,A.R.
  TITLE     Components of a calmodulin-dependent protein kinase cascade.
            Molecular cloning, functional characterization and cellular
            localization of Ca2+/calmodulin-dependent protein kinase kinase
            beta
  JOURNAL   J Biol Chem 273 (48), 31880-31889 (1998)
   PUBMED   9822657
REFERENCE   10 (bases 1 to 4905)
  AUTHORS   Hsu,L.S., Tsou,A.P., Chi,C.W., Lee,C.H. and Chen,J.Y.
  TITLE     Cloning, expression and chromosomal localization of human
            Ca2+/calmodulin-dependent protein kinase kinase
  JOURNAL   J Biomed Sci 5 (2), 141-149 (1998)
   PUBMED   9662074
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA075361.1, AB081336.1,
            AF287630.1, BC026060.2, AL834322.1 and AA678930.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_001270485.1.
            
            Summary: The product of this gene belongs to the Serine/Threonine
            protein kinase family, and to the Ca(2+)/calmodulin-dependent
            protein kinase subfamily. The major isoform of this gene plays a
            role in the calcium/calmodulin-dependent (CaM) kinase cascade by
            phosphorylating the downstream kinases CaMK1 and CaMK4. Protein
            products of this gene also phosphorylate AMP-activated protein
            kinase (AMPK). This gene has its strongest expression in the brain
            and influences signalling cascades involved with learning and
            memory, neuronal differentiation and migration, neurite outgrowth,
            and synapse formation. Alternative splicing results in multiple
            transcript variants encoding distinct isoforms. The identified
            isoforms differ in their ability to undergo autophosphorylation and
            to phosphorylate downstream kinases. [provided by RefSeq, Jul
            2012].
            
            Transcript Variant: This variant (8) differs in the 5' UTR,
            compared to variant 1, and encodes isoform (1). Variants 1 and 8
            encode the same protein (isoform 1).
            
            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 :: SRR14038191.764851.1,
                                           SRR1803615.9309.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000404169.8/ ENSP00000384600.3
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-383               DA075361.1         45-427
            384-1683            AB081336.1         285-1584
            1684-1800           AF287630.1         2376-2492
            1801-2072           BC026060.2         1735-2006
            2073-4820           AL834322.1         1043-3790
            4821-4905           AA678930.1         26-110              c
FEATURES             Location/Qualifiers
     source          1..4905
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q24.31"
     gene            1..4905
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /note="calcium/calmodulin dependent protein kinase kinase
                     2"
                     /db_xref="GeneID:10645"
                     /db_xref="HGNC:HGNC:1470"
                     /db_xref="MIM:615002"
     exon            1..72
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            73..602
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     CDS             132..1898
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /EC_number="2.7.11.17"
                     /note="isoform 1 is encoded by transcript variant 8; CAMKK
                     beta protein; calcium/calmodulin-dependent protein kinase
                     beta; caM-KK 2; caM-KK beta; calcium/calmodulin-dependent
                     protein kinase kinase 2, beta; caM-kinase kinase 2;
                     caM-kinase kinase beta"
                     /codon_start=1
                     /product="calcium/calmodulin-dependent protein kinase
                     kinase 2 isoform 1"
                     /protein_id="NP_001257414.1"
                     /db_xref="CCDS:CCDS9216.1"
                     /db_xref="GeneID:10645"
                     /db_xref="HGNC:HGNC:1470"
                     /db_xref="MIM:615002"
                     /translation="MSSCVSSQPSSNRAAPQDELGGRGSSSSESQKPCEALRGLSSLS
                     IHLGMESFIVVTECEPGCAVDLGLARDRPLEADGQEVPLDTSGSQARPHLSGRKLSLQ
                     ERSQGGLAAGGSLDMNGRCICPSLPYSPVSSPQSSPRLPRRPTVESHHVSITGMQDCV
                     QLNQYTLKDEIGKGSYGVVKLAYNENDNTYYAMKVLSKKKLIRQAGFPRRPPPRGTRP
                     APGGCIQPRGPIEQVYQEIAILKKLDHPNVVKLVEVLDDPNEDHLYMVFELVNQGPVM
                     EVPTLKPLSEDQARFYFQDLIKGIEYLHYQKIIHRDIKPSNLLVGEDGHIKIADFGVS
                     NEFKGSDALLSNTVGTPAFMAPESLSETRKIFSGKALDVWAMGVTLYCFVFGQCPFMD
                     ERIMCLHSKIKSQALEFPDQPDIAEDLKDLITRMLDKNPESRIVVPEIKLHPWVTRHG
                     AEPLPSEDENCTLVEVTEEEVENSVKHIPSLATVILVKTMIRKRSFGNPFEGSRREER
                     SLSAPGNLLTKKPTRECESLSELKEARQRRQPPGHRPAPRGGGGSALVRGSPCVESCW
                     APAPGSPARMHPLRPEEAMEPE"
     exon            603..650
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            651..704
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            705..756
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            757..890
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            891..927
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            928..949
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            950..1038
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1039..1238
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1239..1292
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1293..1366
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1367..1454
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1455..1583
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1584..1684
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1685..1727
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1728..4905
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4879..4884
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /note="hexamer: AATAAA"
     polyA_site      4905
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /note="major polyA site"
ORIGIN      
        1 agagcaagct gagccgagcc gagccgagct gggggcgcag agcgcgggag gcggcggcgg
       61 cgcggagccc aggtggctcc gctgccggat gggagtgccc cagtgtgctg gatgaagctg
      121 gcgcatgcac catgtcatca tgtgtctcta gccagcccag cagcaaccgg gccgcccccc
      181 aggatgagct ggggggcagg ggcagcagca gcagcgaaag ccagaagccc tgtgaggccc
      241 tgcggggcct ctcatccttg agcatccacc tgggcatgga gtccttcatt gtggtcaccg
      301 agtgtgagcc gggctgtgct gtggacctcg gcttggcgcg ggaccggccc ctggaggccg
      361 atggccaaga ggtccccctt gacacctccg ggtcccaggc ccggccccac ctctccggtc
      421 gcaagctgtc tctgcaagag cggtcccagg gtgggctggc agccggtggc agcctggaca
      481 tgaacggacg ctgcatctgc ccgtccctgc cctactcacc cgtcagctcc ccgcagtcct
      541 cgcctcggct gccccggcgg ccgacagtgg agtctcacca cgtctccatc acgggtatgc
      601 aggactgtgt gcagctgaat cagtataccc tgaaggatga aattggaaag ggctcctatg
      661 gtgtcgtcaa gttggcctac aatgaaaatg acaataccta ctatgcaatg aaggtgctgt
      721 ccaaaaagaa gctgatccgg caggccggct ttccacgtcg ccctccaccc cgaggcaccc
      781 ggccagctcc tggaggctgc atccagccca ggggccccat tgagcaggtg taccaggaaa
      841 ttgccatcct caagaagctg gaccacccca atgtggtgaa gctggtggag gtcctggatg
      901 accccaatga ggaccatctg tacatggtgt tcgaactggt caaccaaggg cccgtgatgg
      961 aagtgcccac cctcaaacca ctctctgaag accaggcccg tttctacttc caggatctga
     1021 tcaaaggcat cgagtactta cactaccaga agatcatcca ccgtgacatc aaaccttcca
     1081 acctcctggt cggagaagat gggcacatca agatcgctga ctttggtgtg agcaatgaat
     1141 tcaagggcag tgacgcgctc ctctccaaca ccgtgggcac gcccgccttc atggcacccg
     1201 agtcgctctc tgagacccgc aagatcttct ctgggaaggc cttggatgtt tgggccatgg
     1261 gtgtgacact atactgcttt gtctttggcc agtgcccatt catggacgag cggatcatgt
     1321 gtttacacag taagatcaag agtcaggccc tggaatttcc agaccagccc gacatagctg
     1381 aggacttgaa ggacctgatc acccgtatgc tggacaagaa ccccgagtcg aggatcgtgg
     1441 tgccggaaat caagctgcac ccctgggtca cgaggcatgg ggcggagccg ttgccgtcgg
     1501 aggatgagaa ctgcacgctg gtcgaagtga ctgaagagga ggtcgagaac tcagtcaaac
     1561 acattcccag cttggcaacc gtgatcctgg tgaagaccat gatacgtaaa cgctcctttg
     1621 ggaacccatt cgagggcagc cggcgggagg aacgctcact gtcagcgcct ggaaacttgc
     1681 tcaccaaaaa accaaccagg gaatgtgagt ccctgtctga gctcaaggaa gcaaggcagc
     1741 gaagacaacc tccagggcac cgacccgccc cccgtggggg aggaggaagt gctcttgtga
     1801 gaggcagtcc ctgcgtggaa agttgctggg cccccgcccc cggctccccc gcacgcatgc
     1861 atccactgcg gccggaggag gccatggagc ccgagtagct gcctggatcg ctcgacctcg
     1921 catgcgcgcc gcgtcgcctc tggggggctg ctgcaccgcg tttccatagc agcatgtcct
     1981 acggaaaccc agcacgtgtg tagagcctcg atcgtcatct ctggttattt gttttttcct
     2041 ttgttgtttt aaaggggaca aaaaaaaaaa aaggacttga ctccatgacg tcgaccgtgg
     2101 ccgctggctg gctggacagg cgggtgtgag gagttgcaga cccaaaccca cgtgcatttt
     2161 gggacaattg ctttttaaaa cgtttttatg ccaaaaatcc ttcattgtga ttttcagaac
     2221 cacgtcagat ataccaagtg actgtgtgtg gggtttgaca actgtggaaa ggcgagcaga
     2281 aaactccggc ggtctgaggc catggaggtg gttgctgcat ttgagaggga gtagggggct
     2341 agatgtggct cctagtgcaa accggaaacc atggcacctt ccagagccgt ggtctcaagg
     2401 agtcagagca gggctggccc tcagtagctg cagggagctt tgatgcaact tatttgtaag
     2461 aaggattttt aaatttttta tgggtagaat tgtagtcagg aaaacagaaa gggcttgaaa
     2521 tttaataagt gctgctggaa ggggattttc caagcctgga agggtattca gcagctgtgg
     2581 tggggaaaca tttctcctga aagactgaac gtgtttcttc atgacagctg ctcaaagcag
     2641 gtttctgaga tagctgaccg agctctggta aatctctttg tcaaattacg aaaacttcag
     2701 ggtgaaatcc tatgcttcca tgtacattac atggcttaag attaaacaaa aacatttttc
     2761 aagtctctaa ctagagtgaa ctctagagca cagtagttca gaaactattt agagcttcca
     2821 ggatatattt cacagcttca ggcatgtgat cagttagagc cgatgaaacc tatgcccgcc
     2881 tgtatatata ttagcagctt agctagttca taacctgtat attctaaaga ctgctaaggt
     2941 tttgttttca ttttaaatcc tagctgattg ttgtggtcaa tgaaataccc agtttctgga
     3001 gggccaggtg ggaaatgctt tcactggacc aacacacaaa tgatcatcct gaggatctga
     3061 gcttccctag actccacaca ataaccttgg ggcacccttt tagagaagac tgttgaaacc
     3121 cacagcactc gttggggtat gaggaaacca gggcttggca caggaagttc ccctttgtag
     3181 ctaaaagtcc agaaagaaag ggttcatctt tttgacttcc aactgatatt gggaagtttg
     3241 gttgaggttc aagtgtgact ccttccagag ccacaggtag gggagtgtga agttgagggg
     3301 gaggaaagct ggaaggactc tgccttggga gattcccagc tctgctttcc agcgcttggt
     3361 ggaatctggg ctggggaaag acggcaccgg gaaactctgc ttccccattg tttccatctg
     3421 atcagctgtg gtgtgaggac ttctcagaca aaggcaaggc ctcgtgcccc tgcccagccc
     3481 attcatggag ccctgggcct tcttggcttc catagatcct aagctcttga ctgtagttta
     3541 gccagacttg ttttgctatc ttataagcag ttcagaatta gggaatgctg gttttgaaga
     3601 gcaaaggaca ggtagtctag agagggtcgt ctggcctgct tgctgggtct ttgtaaccca
     3661 gcacttcctc ttgccctcct ggctttatgt ttatggggag aggactcaat agctccaccc
     3721 cttctggcac cagatggggc ttggttagtt tgcaataagc accttgcaga ggttaaagcc
     3781 agcgggtccc tagtcttagg cccagcctgc ttgtgtgggc tctggcctgg cctggtggct
     3841 ggcccagggg gcagcagtgc ttagagcttc tgcagggctt ctcttgttta cacagctgca
     3901 tcagacaatg ccatttctcc ccaccacgga accttccatc taagatttct tccagggaat
     3961 gccagcaatc aggcagcacc cagctgtggg ggcagtgggg tgggggagac ccacattgat
     4021 gacttttttt ttttctttta atgaagaaac accaaagaaa gctgtggaaa ggacctgccc
     4081 cacatgaaaa ggataagcca agatggctgt aaacacagag catttgagct gccactcttg
     4141 gagcacattg atttttcaaa agccagctct gtcaggaaag gaggtgctgt tatgagcagc
     4201 tcttccagtg ggcaaagagg acgcccataa tttcttccat tgctagctca tctgtgggac
     4261 caatttggtg taagcaacct gtggcctgca cttgtggcct cgaaggaagc acaaaccctc
     4321 catccacttc ccatttcctc tgcccttttc cacctccccc ttccatccca ccagctgcca
     4381 gtggctccca gaaagcctta ttgagcccct tgttgacact tggggctgcg gaggcctctc
     4441 cctactggtc tggcctttcc tgagaggcag gtcttccgtc ctcagagcct ttctggaaca
     4501 aggagaatgc ctgtgcaggt ggacacacag gcctggcctg tcgctctcac ttgtcttcca
     4561 gcggggagct tcacgttgcc gagtggaaga accatgacct ccacttgctt ccaaggtgct
     4621 agggaagttt cagggtacgc tggttcccct ctccagctgg aggccgagtt tctggggact
     4681 gcagattttt ctactctgtg atcgattcaa tgcccgatgc ttctgtttca ttcccgaccc
     4741 tttctactat gcattttcct tttatcaggt gtataaagtt aaatactgtg tatttatcac
     4801 taaaaagtac atgaacttaa gagacaacta agcctttcgt gtttttccac aggtgtttaa
     4861 gcttctctgt acagttgaaa taaacagaca gcaaaatggt gccaa
//
