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

Gene ID: 10645, updated on 15-Apr-2019

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
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

Genomic context

See CAMKK2 in Genome Data Viewer
Location:
12q24.31
Exon count:
20
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 12 NC_000012.12 (121237692..121298308, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (121675495..121736111, complement)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370032 Neighboring gene purinergic receptor P2X 7 Neighboring gene purinergic receptor P2X 4 Neighboring gene anaphase promoting complex subunit 5 Neighboring gene ring finger protein 34 Neighboring gene lysine demethylase 2B

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 FunctionsWhat'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 BioSystems

  • AMP-activated Protein Kinase (AMPK) Signaling, organism-specific biosystem (from WikiPathways)
    AMP-activated Protein Kinase (AMPK) Signaling, organism-specific biosystemAMPK signaling pathway, a fuel sensor and regulator, promotes ATP-producing and inhibits ATP-consuming pathways in various tissues. AMPK is a heterotrimer composed of alpha-catalytic and beta and gam...
  • AMPK signaling pathway, organism-specific biosystem (from KEGG)
    AMPK signaling pathway, organism-specific biosystemAMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in th...
  • AMPK signaling pathway, conserved biosystem (from KEGG)
    AMPK signaling pathway, conserved biosystemAMP-activated protein kinase (AMPK) is a serine threonine kinase that is highly conserved through evolution. AMPK system acts as a sensor of cellular energy status. It is activated by increases in th...
  • Adipocytokine signaling pathway, organism-specific biosystem (from KEGG)
    Adipocytokine signaling pathway, organism-specific biosystemIncreased adipocyte volume and number are positively correlated with leptin production, and negatively correlated with production of adiponectin. Leptin is an important regulator of energy intake and...
  • Adipocytokine signaling pathway, conserved biosystem (from KEGG)
    Adipocytokine signaling pathway, conserved biosystemIncreased adipocyte volume and number are positively correlated with leptin production, and negatively correlated with production of adiponectin. Leptin is an important regulator of energy intake and...
  • Alcoholism, organism-specific biosystem (from KEGG)
    Alcoholism, organism-specific biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
  • Alcoholism, conserved biosystem (from KEGG)
    Alcoholism, conserved biosystemAlcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the reward...
  • Autophagy - animal, organism-specific biosystem (from KEGG)
    Autophagy - animal, organism-specific biosystemAutophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily cons...
  • Autophagy - animal, conserved biosystem (from KEGG)
    Autophagy - animal, conserved biosystemAutophagy (or macroautophagy) is a cellular catabolic pathway involving in protein degradation, organelle turnover, and non-selective breakdown of cytoplasmic components, which is evolutionarily cons...
  • Longevity regulating pathway, organism-specific biosystem (from KEGG)
    Longevity regulating pathway, organism-specific biosystemRegulation of longevity depends on genetic and environmental factors. Caloric restriction (CR), that is limiting food intake, is recognized in mammals as the best characterized and most reproducible ...
  • Oxytocin signaling pathway, organism-specific biosystem (from KEGG)
    Oxytocin signaling pathway, organism-specific biosystemOxytocin (OT) is a nonapeptide synthesized by the magno-cellular neurons located in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. It exerts a wide variety of central and ...
  • Oxytocin signaling pathway, conserved biosystem (from KEGG)
    Oxytocin signaling pathway, conserved biosystemOxytocin (OT) is a nonapeptide synthesized by the magno-cellular neurons located in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. It exerts a wide variety of central and ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • KIAA0787, MGC15254

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
calcium ion binding IDA
Inferred from Direct Assay
more info
PubMed 
calmodulin binding TAS
Traceable Author Statement
more info
PubMed 
calmodulin-dependent protein kinase activity IEA
Inferred from Electronic Annotation
more info
 
protein tyrosine kinase activity TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
cell projection IEA
Inferred from Electronic Annotation
more info
 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol IMP
Inferred from Mutant Phenotype
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
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_016874183.1
XP_016874184.1
XP_016874188.1
XP_016874189.1
XP_016874191.1
XP_016874192.1
XP_016874194.1
XP_016874195.1
XP_016874197.1
XP_016874198.1
XP_024304566.1
XP_024304567.1

NCBI Reference Sequences (RefSeq)

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
    5001..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
    Q96RR4
    UniProtKB/TrEMBL
    A0A024RBQ0
    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/Swiss-Prot
    Q96RR4
    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_006549.3NP_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)
    AF287630
    Consensus CDS
    CCDS9216.1
    UniProtKB/Swiss-Prot
    Q96RR4
    UniProtKB/TrEMBL
    A0A024RBQ0
    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_153499.2NP_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)
    AF287630, AF321387
    Consensus CDS
    CCDS9218.1
    UniProtKB/Swiss-Prot
    Q96RR4
    UniProtKB/TrEMBL
    A0A024RBP6
    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_153500.1NP_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)
    AF287630, AF321388
    Consensus CDS
    CCDS9219.1
    UniProtKB/Swiss-Prot
    Q96RR4
    UniProtKB/TrEMBL
    A0A024RBQ3
    Related
    ENSP00000445944.1, ENST00000538733.5
    Conserved Domains (1) summary
    cl21453
    Location:162442
    PKc_like; Protein Kinases, catalytic domain
  6. NM_172214.2NP_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/Swiss-Prot
    Q96RR4
    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_172215.2NP_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/Swiss-Prot
    Q96RR4
    Related
    ENSP00000388273.2, ENST00000446440.6
    Conserved Domains (1) summary
    cl21453
    Location:162442
    PKc_like; Protein Kinases, catalytic domain
  8. NM_172216.1NP_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)
    AF287630, AF321386
    Consensus CDS
    CCDS9217.1
    UniProtKB/Swiss-Prot
    Q96RR4
    UniProtKB/TrEMBL
    A0A024RBP8
    Related
    ENSP00000321230.3, ENST00000347034.6
    Conserved Domains (1) summary
    cl21453
    Location:162442
    PKc_like; Protein Kinases, catalytic domain
  9. NM_172226.2NP_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/Swiss-Prot
    Q96RR4
    UniProtKB/TrEMBL
    A0A024RBP6
    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: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p12 Primary Assembly

    Range
    121237692..121298308 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017018695.1XP_016874184.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X1

  2. XM_017018702.2XP_016874191.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X4

    UniProtKB/Swiss-Prot
    Q96RR4
    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. XM_017018709.2XP_016874198.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X14

    Conserved Domains (1) summary
    cl21453
    Location:1172
    PKc_like; Protein Kinases, catalytic domain
  4. XM_005253824.3XP_005253881.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X9

    See identical proteins and their annotated locations for XP_005253881.1

    UniProtKB/Swiss-Prot
    Q96RR4
    UniProtKB/TrEMBL
    A0A024RBQ3
    Conserved Domains (1) summary
    cl21453
    Location:162442
    PKc_like; Protein Kinases, catalytic domain
  5. XM_005253822.3XP_005253879.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X6

    See identical proteins and their annotated locations for XP_005253879.1

    UniProtKB/TrEMBL
    A0A024RBP8
    Conserved Domains (1) summary
    cl21453
    Location:162442
    PKc_like; Protein Kinases, catalytic domain
  6. XM_011537763.1XP_011536065.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X4

    See identical proteins and their annotated locations for XP_011536065.1

    UniProtKB/Swiss-Prot
    Q96RR4
    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
  7. XM_017018706.1XP_016874195.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X11

  8. XM_011537764.2XP_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
  9. XM_017018705.1XP_016874194.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X8

  10. XM_017018699.1XP_016874188.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X2

  11. XM_017018700.1XP_016874189.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X3

  12. XM_017018694.1XP_016874183.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X1

  13. XM_024448799.1XP_024304567.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X14

    Conserved Domains (1) summary
    cl21453
    Location:1172
    PKc_like; Protein Kinases, catalytic domain
  14. XM_024448798.1XP_024304566.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X12

    Conserved Domains (1) summary
    cl21453
    Location:9283
    PKc_like; Protein Kinases, catalytic domain
  15. XM_005253823.1XP_005253880.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X7

    See identical proteins and their annotated locations for XP_005253880.1

    UniProtKB/Swiss-Prot
    Q96RR4
    Conserved Domains (1) summary
    cd14199
    Location:162447
    STKc_CaMKK2; Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2
  16. XM_017018708.1XP_016874197.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X13

  17. XM_017018703.1XP_016874192.1  calcium/calmodulin-dependent protein kinase kinase 2 isoform X5

RNA

  1. XR_001748557.1 RNA Sequence

  2. XR_001748558.1 RNA Sequence

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