LOCUS       NM_172214               2478 bp    mRNA    linear   PRI 19-AUG-2024
DEFINITION  Homo sapiens calcium/calmodulin dependent protein kinase kinase 2
            (CAMKK2), transcript variant 5, mRNA.
ACCESSION   NM_172214
VERSION     NM_172214.3
KEYWORDS    RefSeq.
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 2478)
  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 2478)
  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 2478)
  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 2478)
  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 2478)
  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 2478)
  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 2478)
  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 2478)
  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 2478)
  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 2478)
  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 AC069209.38 and AF287631.1.
            
            On May 31, 2019 this sequence version replaced NM_172214.2.
            
            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 (5), also known as beta 2,
            contains an alternate segment in the 3' coding region and differs
            in the 3' UTR, compared to variant 1. The encoded isoform (5) is
            shorter and has a distinct C-terminus, compared to isoform 1.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 :: AF287631.1, SRR1803611.21968.1
                                           [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-281               AC069209.38        131334-131614       c
            282-811             AC069209.38        107851-108380       c
            812-859             AC069209.38        104693-104740       c
            860-913             AC069209.38        103323-103376       c
            914-965             AC069209.38        102433-102484       c
            966-1099            AC069209.38        97601-97734         c
            1100-1136           AC069209.38        94114-94150         c
            1137-1158           AC069209.38        89578-89599         c
            1159-1247           AC069209.38        89345-89433         c
            1248-1447           AC069209.38        87068-87267         c
            1448-1501           AC069209.38        86456-86509         c
            1502-1575           AC069209.38        83756-83829         c
            1576-1663           AC069209.38        83582-83669         c
            1664-1792           AC069209.38        82401-82529         c
            1793-1893           AC069209.38        78935-79035         c
            1894-1936           AC069209.38        78368-78410         c
            1937-2333           AC069209.38        77528-77924         c
            2334-2478           AF287631.1         2817-2961
FEATURES             Location/Qualifiers
     source          1..2478
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q24.31"
     gene            1..2478
                     /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..281
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            282..811
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     CDS             341..1942
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /EC_number="2.7.11.17"
                     /note="isoform 5 is encoded by transcript variant 5; 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 5"
                     /protein_id="NP_757363.1"
                     /db_xref="CCDS:CCDS44999.1"
                     /db_xref="GeneID:10645"
                     /db_xref="HGNC:HGNC:1470"
                     /db_xref="MIM:615002"
                     /translation="MSSCVSSQPSSNRAAPQDELGGRGSSSSESQKPCEALRGLSSLS
                     IHLGMESFIVVTECEPGCAVDLGLARDRPLEADGQEVPLDTSGSQARPHLSGRKLSLQ
                     ERSQGGLAAGGSLDMNGRCICPSLPYSPVSSPQSSPRLPRRPTVESHHVSITGMQDCV
                     QLNQYTLKDEIGKGSYGVVKLAYNENDNTYYAMKVLSKKKLIRQAGFPRRPPPRGTRP
                     APGGCIQPRGPIEQVYQEIAILKKLDHPNVVKLVEVLDDPNEDHLYMVFELVNQGPVM
                     EVPTLKPLSEDQARFYFQDLIKGIEYLHYQKIIHRDIKPSNLLVGEDGHIKIADFGVS
                     NEFKGSDALLSNTVGTPAFMAPESLSETRKIFSGKALDVWAMGVTLYCFVFGQCPFMD
                     ERIMCLHSKIKSQALEFPDQPDIAEDLKDLITRMLDKNPESRIVVPEIKLHPWVTRHG
                     AEPLPSEDENCTLVEVTEEEVENSVKHIPSLATVILVKTMIRKRSFGNPFEGSRREER
                     SLSAPGNLLTKKPTRECESLSELKT"
     exon            812..859
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            860..913
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            914..965
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            966..1099
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1100..1136
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1137..1158
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1159..1247
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1248..1447
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1448..1501
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1502..1575
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1576..1663
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1664..1792
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1793..1893
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1894..1936
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     exon            1937..2478
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2458..2463
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /note="hexamer: TATAAA"
     polyA_site      2478
                     /gene="CAMKK2"
                     /gene_synonym="CAMKK; CAMKKB"
                     /note="major polyA site"
ORIGIN      
        1 gagtgtccct acggcctaga aatacaagag aagcacatcg gaacgggctg gaaatccacc
       61 cagttaacta gagggctttg aaccttttat taacttggag gttgactctc ctgtcaactc
      121 gattcccttt tggctgtttg gcagggtcag tgagacatcc cctgggtcgc tcgaccccgt
      181 aggacggttc agggagccct ccaggtcttc gtttctcctc ttccccgcac agtgctgtta
      241 tccagctggg ggatccaacg cacacttaag gctccagcaa agtggctccg ctgccggatg
      301 ggagtgcccc agtgtgctgg atgaagctgg cgcatgcacc atgtcatcat gtgtctctag
      361 ccagcccagc agcaaccggg ccgcccccca ggatgagctg gggggcaggg gcagcagcag
      421 cagcgaaagc cagaagccct gtgaggccct gcggggcctc tcatccttga gcatccacct
      481 gggcatggag tccttcattg tggtcaccga gtgtgagccg ggctgtgctg tggacctcgg
      541 cttggcgcgg gaccggcccc tggaggccga tggccaagag gtcccccttg acacctccgg
      601 gtcccaggcc cggccccacc tctccggtcg caagctgtct ctgcaagagc ggtcccaggg
      661 tgggctggca gccggtggca gcctggacat gaacggacgc tgcatctgcc cgtccctgcc
      721 ctactcaccc gtcagctccc cgcagtcctc gcctcggctg ccccggcggc cgacagtgga
      781 gtctcaccac gtctccatca cgggtatgca ggactgtgtg cagctgaatc agtataccct
      841 gaaggatgaa attggaaagg gctcctatgg tgtcgtcaag ttggcctaca atgaaaatga
      901 caatacctac tatgcaatga aggtgctgtc caaaaagaag ctgatccggc aggccggctt
      961 tccacgtcgc cctccacccc gaggcacccg gccagctcct ggaggctgca tccagcccag
     1021 gggccccatt gagcaggtgt accaggaaat tgccatcctc aagaagctgg accaccccaa
     1081 tgtggtgaag ctggtggagg tcctggatga ccccaatgag gaccatctgt acatggtgtt
     1141 cgaactggtc aaccaagggc ccgtgatgga agtgcccacc ctcaaaccac tctctgaaga
     1201 ccaggcccgt ttctacttcc aggatctgat caaaggcatc gagtacttac actaccagaa
     1261 gatcatccac cgtgacatca aaccttccaa cctcctggtc ggagaagatg ggcacatcaa
     1321 gatcgctgac tttggtgtga gcaatgaatt caagggcagt gacgcgctcc tctccaacac
     1381 cgtgggcacg cccgccttca tggcacccga gtcgctctct gagacccgca agatcttctc
     1441 tgggaaggcc ttggatgttt gggccatggg tgtgacacta tactgctttg tctttggcca
     1501 gtgcccattc atggacgagc ggatcatgtg tttacacagt aagatcaaga gtcaggccct
     1561 ggaatttcca gaccagcccg acatagctga ggacttgaag gacctgatca cccgtatgct
     1621 ggacaagaac cccgagtcga ggatcgtggt gccggaaatc aagctgcacc cctgggtcac
     1681 gaggcatggg gcggagccgt tgccgtcgga ggatgagaac tgcacgctgg tcgaagtgac
     1741 tgaagaggag gtcgagaact cagtcaaaca cattcccagc ttggcaaccg tgatcctggt
     1801 gaagaccatg atacgtaaac gctcctttgg gaacccattc gagggcagcc ggcgggagga
     1861 acgctcactg tcagcgcctg gaaacttgct caccaaaaaa ccaaccaggg aatgtgagtc
     1921 cctgtctgag ctcaagacct agaaaataag tccccttcct gcctgttgca aagtaacgta
     1981 agagttccct cacccgagtg gatgcagacc ttcttgctgt cagccaccct tccttcatac
     2041 acatagccag cccaggtgac cagaacctcc caggacagat gaggctttgt gtccttatga
     2101 gactgggaga acctgctggg cacccctgct gcaggtgctg tggtgggtgg ggaccccact
     2161 gcccttccca ctgagcacat catggctacc tgacttggtg ggagctccag gcagtcactt
     2221 ctgtttctta aacatagctt tactgaggta caattcacat accatgtaat tcacccacgg
     2281 gaagtgtatg attcagtggt ttctaataca gacttctgca gccattacca ccgtcaactt
     2341 tacgacattt tcatcagccc aagaagacac cctacactcc ttagctgtcc ccatccaact
     2401 cccccacccc agtaaccact cagaataggt atggatttgc ctattctgga cgtttcgtat
     2461 aaatggcgtc atacacta
//
