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

Gene ID: 10645, updated on 2-Nov-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
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Genomic context

See CAMKK2 in Genome Data Viewer
Location:
12q24.31
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (121237692..121297819, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (121228458..121289212, complement)
RS_2024_09 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 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 calcium/calmodulin-dependent protein kinase activity IEA
Inferred from Electronic Annotation
more info
 
enables calmodulin binding TAS
Traceable Author Statement
more info
PubMed 
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_2024_08

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