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    CAMKK2 calcium/calmodulin dependent protein kinase kinase 2 [ Homo sapiens (human) ]

    Gene ID: 10645, updated on 3-Apr-2024

    Summary

    Official Symbol
    CAMKK2provided by HGNC
    Official Full Name
    calcium/calmodulin dependent protein kinase kinase 2provided by HGNC
    Primary source
    HGNC:HGNC:1470
    See related
    Ensembl:ENSG00000110931 MIM:615002; AllianceGenome:HGNC:1470
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CAMKK; CAMKKB
    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]
    Expression
    Ubiquitous expression in brain (RPKM 24.4), spleen (RPKM 11.0) and 24 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Location:
    12q24.31
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (121237692..121297819, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (121228458..121289212, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (121675495..121735622, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370032 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7157 Neighboring gene NANOG hESC enhancer GRCh37_chr12:121593595-121594096 Neighboring gene purinergic receptor P2X 7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121627731-121628231 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4970 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7158 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121661200-121661700 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7159 Neighboring gene Sharpr-MPRA regulatory region 10951 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121671545-121672172 Neighboring gene purinergic receptor P2X 4 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4971 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:121683587-121683800 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7161 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121693396-121693896 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121720271-121720878 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121720879-121721486 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4972 Neighboring gene anaphase promoting complex subunit 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:121773208-121773399 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:121789289-121789964 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7162 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:121790641-121791316 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:121791317-121791990 Neighboring gene uncharacterized LOC124903037 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7163

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    Knockdown of calcium/calmodulin-dependent protein kinase kinase 2, beta (CAMKK2) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat Knockdown of calcium/calmodulin-dependent protein kinase kinase 2 beta (CAMKK2) by siRNAs inhibits HIV LTR-beta-gal activation in the Tat transactivation assay PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • KIAA0787, MGC15254

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables calcium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables calmodulin binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables calmodulin-dependent protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in neuron projection IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    calcium/calmodulin-dependent protein kinase kinase 2
    Names
    CAMKK beta protein
    caM-KK 2
    caM-KK beta
    caM-kinase kinase 2
    caM-kinase kinase beta
    calcium/calmodulin-dependent protein kinase beta
    calcium/calmodulin-dependent protein kinase kinase 2, beta
    NP_001257414.1
    NP_001257415.1
    NP_006540.3
    NP_705719.2
    NP_705720.1
    NP_757363.1
    NP_757364.1
    NP_757365.1
    NP_757380.1
    XP_005253879.1
    XP_005253880.1
    XP_005253881.1
    XP_011536065.1
    XP_011536066.1
    XP_016874191.1
    XP_047284057.1
    XP_047284058.1
    XP_047284059.1
    XP_047284060.1
    XP_047284061.1
    XP_047284062.1
    XP_047284063.1
    XP_047284064.1
    XP_047284065.1
    XP_054226771.1
    XP_054226772.1
    XP_054226773.1
    XP_054226774.1
    XP_054226775.1
    XP_054226776.1
    XP_054226777.1
    XP_054226778.1
    XP_054226779.1
    XP_054226780.1
    XP_054226781.1
    XP_054226782.1
    XP_054226783.1
    XP_054226784.1
    XP_054226785.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029409.1 RefSeqGene

      Range
      6600..65617
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001270485.2NP_001257414.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform 1

      See identical proteins and their annotated locations for NP_001257414.1

      Status: REVIEWED

      Description
      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).
      Source sequence(s)
      AA678930, AB081336, AF287630, AL834322, BC026060, DA075361
      Consensus CDS
      CCDS9216.1
      UniProtKB/Swiss-Prot
      A8K7Q7, O94883, Q8IUG2, Q8IUG3, Q8N3I4, Q8WY03, Q8WY04, Q8WY05, Q8WY06, Q96RP1, Q96RP2, Q96RR3, Q96RR4, Q9BWE9, Q9UER3, Q9UES2, Q9Y5N2
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000384600.3, ENST00000404169.8
      Conserved Domains (1) summary
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
    2. NM_001270486.1NP_001257415.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform 7

      See identical proteins and their annotated locations for NP_001257415.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) lacks a segment in the 3' coding region and 3' UTR, which leads to a frameshift, compared to variant 1. The resulting isoform (7) contains a shorter and distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AA678930, AB018330, AF321385, AL834322
      Consensus CDS
      CCDS58283.1
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000376266.2, ENST00000392474.6
      Conserved Domains (2) summary
      smart00220
      Location:165446
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
    3. NM_006549.4NP_006540.3  calcium/calmodulin-dependent protein kinase kinase 2 isoform 1

      See identical proteins and their annotated locations for NP_006540.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1), also known as beta 1, represents the longest transcript, and encodes the longest isoform (1). Variants 1 and 8 encode the same protein (isoform 1).
      Source sequence(s)
      AC069209
      Consensus CDS
      CCDS9216.1
      UniProtKB/Swiss-Prot
      A8K7Q7, O94883, Q8IUG2, Q8IUG3, Q8N3I4, Q8WY03, Q8WY04, Q8WY05, Q8WY06, Q96RP1, Q96RP2, Q96RR3, Q96RR4, Q9BWE9, Q9UER3, Q9UES2, Q9Y5N2
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000312741.5, ENST00000324774.9
      Conserved Domains (1) summary
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
    4. NM_153499.3NP_705719.2  calcium/calmodulin-dependent protein kinase kinase 2 isoform 2

      See identical proteins and their annotated locations for NP_705719.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), also known as beta 1del16, lacks a segment in the coding region, which leads to a frameshift, compared to variant 1. The resulting isoform (2) contains a shorter and distinct C-terminus compared to isoform 1. This isoform (2) is also encoded by variant 7.
      Source sequence(s)
      AC069209
      Consensus CDS
      CCDS9218.1
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000336634.3, ENST00000337174.7
      Conserved Domains (1) summary
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
    5. NM_153500.2NP_705720.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform 4

      See identical proteins and their annotated locations for NP_705720.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), also known as beta 1del14del16, has multiple differences in the coding region, compared to variant 1, one of which results in a translational frameshift. The resulting isoform (4) has a distinct C-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC069209
      Consensus CDS
      CCDS9219.1
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000445944.1, ENST00000538733.5
      Conserved Domains (1) summary
      cl21453
      Location:162442
      PKc_like; Protein Kinases, catalytic domain
    6. NM_172214.3NP_757363.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform 5

      See identical proteins and their annotated locations for NP_757363.1

      Status: REVIEWED

      Description
      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.
      Source sequence(s)
      AC069209, AF287631
      Consensus CDS
      CCDS44999.1
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000376265.2, ENST00000392473.2
      Conserved Domains (1) summary
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
    7. NM_172215.3NP_757364.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform 6

      See identical proteins and their annotated locations for NP_757364.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6), also known as beta 2del14, differs in the 3' UTR and has multiple coding region differences, compared to variant 1. This results in a shorter isoform (6) with a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AC069209, AF287631
      Consensus CDS
      CCDS53837.1
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000388273.2, ENST00000446440.6
      Conserved Domains (1) summary
      cl21453
      Location:162442
      PKc_like; Protein Kinases, catalytic domain
    8. NM_172216.2NP_757365.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform 3

      See identical proteins and their annotated locations for NP_757365.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), also known as beta 1del14, lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (3), that is missing an internal segment compared to isoform 1.
      Source sequence(s)
      AC069209
      Consensus CDS
      CCDS9217.1
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000321230.3, ENST00000347034.6
      Conserved Domains (1) summary
      cl21453
      Location:162442
      PKc_like; Protein Kinases, catalytic domain
    9. NM_172226.3NP_757380.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform 2

      See identical proteins and their annotated locations for NP_757380.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) differs in the 5' UTR and also lacks a segment in the coding region, which leads to a frameshift, compared to variant 1. The resulting isoform (2) contains a shorter and distinct C-terminus compared to isoform 1. This isoform (2) is also encoded by variant 2.
      Source sequence(s)
      AB018330, AC069209, AI612762, BC026060, DA075361
      Consensus CDS
      CCDS9218.1
      UniProtKB/TrEMBL
      B4DV02
      Related
      ENSP00000388368.2, ENST00000412367.6
      Conserved Domains (1) summary
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      121237692..121297819 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017018702.3XP_016874191.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X2

      UniProtKB/TrEMBL
      B4DV02
      Conserved Domains (2) summary
      smart00220
      Location:165446
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
    2. XM_005253824.3XP_005253881.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X8

      See identical proteins and their annotated locations for XP_005253881.1

      UniProtKB/TrEMBL
      B4DV02
      Conserved Domains (1) summary
      cl21453
      Location:162442
      PKc_like; Protein Kinases, catalytic domain
    3. XM_047428105.1XP_047284061.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X6

    4. XM_005253822.3XP_005253879.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X3

      See identical proteins and their annotated locations for XP_005253879.1

      UniProtKB/TrEMBL
      B4DV02
      Conserved Domains (1) summary
      cl21453
      Location:162442
      PKc_like; Protein Kinases, catalytic domain
    5. XM_011537763.1XP_011536065.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X2

      See identical proteins and their annotated locations for XP_011536065.1

      UniProtKB/TrEMBL
      B4DV02
      Conserved Domains (2) summary
      smart00220
      Location:165446
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
    6. XM_047428107.1XP_047284063.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X8

    7. XM_047428103.1XP_047284059.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X4

    8. XM_047428102.1XP_047284058.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X2

    9. XM_047428101.1XP_047284057.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      A8K7Q7, O94883, Q8IUG2, Q8IUG3, Q8N3I4, Q8WY03, Q8WY04, Q8WY05, Q8WY06, Q96RP1, Q96RP2, Q96RR3, Q96RR4, Q9BWE9, Q9UER3, Q9UES2, Q9Y5N2
    10. XM_011537764.3XP_011536066.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X10

      Conserved Domains (2) summary
      smart00220
      Location:9282
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl21453
      Location:9283
      PKc_like; Protein Kinases, catalytic domain
    11. XM_047428109.1XP_047284065.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X11

    12. XM_047428108.1XP_047284064.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X9

    13. XM_005253823.1XP_005253880.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X5

      See identical proteins and their annotated locations for XP_005253880.1

      UniProtKB/TrEMBL
      B4DV02
      Conserved Domains (1) summary
      cd14199
      Location:162447
      STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
    14. XM_047428104.1XP_047284060.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X5

    15. XM_047428106.1XP_047284062.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X7

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      121228458..121289212 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054370799.1XP_054226774.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X2

    2. XM_054370806.1XP_054226781.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X8

    3. XM_054370804.1XP_054226779.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X6

    4. XM_054370800.1XP_054226775.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X3

    5. XM_054370797.1XP_054226772.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X2

    6. XM_054370807.1XP_054226782.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X8

    7. XM_054370801.1XP_054226776.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X4

    8. XM_054370798.1XP_054226773.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X2

    9. XM_054370796.1XP_054226771.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X1

      UniProtKB/Swiss-Prot
      A8K7Q7, O94883, Q8IUG2, Q8IUG3, Q8N3I4, Q8WY03, Q8WY04, Q8WY05, Q8WY06, Q96RP1, Q96RP2, Q96RR3, Q96RR4, Q9BWE9, Q9UER3, Q9UES2, Q9Y5N2
    10. XM_054370809.1XP_054226784.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X10

    11. XM_054370810.1XP_054226785.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X11

    12. XM_054370808.1XP_054226783.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X9

    13. XM_054370802.1XP_054226777.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X5

    14. XM_054370803.1XP_054226778.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X5

    15. XM_054370805.1XP_054226780.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X7