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FLASH GENE

Symbol

CAMKK2

contributors: mct - updated : 08-03-2023

HGNC name	calcium/calmodulin-dependent protein kinase kinase 2, beta
HGNC id	1470

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	12q24.31      Physical location : 121.675.495 - 121.736.111
Synonym name	CAMKK beta protein
	CaM-kinase kinase beta
Synonym symbol(s)	KIAA0787, CAMKBB, CAMKK, CAMKKB, MGC15254
EC.number	2.7.11.17

DNA

TYPE	functioning gene
STRUCTURE	60.62 kb     17 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D12S366 - D12S86 - D12S349 - D12S321 - CAMKK2 - D12S342 - D12S340 - qter
Authors	Gene Map (98)

RNA

TRANSCRIPTS	type	messenger

text	several transcripts resulting from alternative polyadenylation and/or splicing of exons 14 and/or 16 (PMID: 11395482)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006549 17 initiation site 5620 NP_006540 64.6 588 - 2008 18436530 also known as beta 1 NM_172214 17 polyA site 2981 NP_757363 58.8 533 - 2008 18436530 also known as beta 2 containing an alternate segment in the 3' coding region and differing in the 3' UTR compared to variant 1 NM_153499 16 splicing 5577 PMID: 18436530 59.5 541 - 2008 18436530 also known as beta 1del16 lacking a segment in the coding region which leads to a frameshift compared to variant 1 encoding the same protein than variant 7 NM_172216 16 splicing 5491 NP_757365 59.8 545 - 2008 18436530 also known as beta 1del14 lacking an in-frame segment of the coding region compared to variant 1 NM_153500 15 - 5448 NP_705720 54.7 498 - 2008 18436530 also known as beta 1del14del16 having multiple differences in the coding region compared to variant 1, one of which results in a translational frameshift NM_172226 16 splicing 4923 NP_757380 59.5 541 - 2008 18436530 differing in the 5' UTR and also lacking a segment in the coding region, which leads to a frameshift compared to variant 1 encoding the same protein than variant 2 NM_172215 16 splicing 2852 NP_757364 54 490 - 2008 18436530 also known as beta 2del14 differing in the 3' UTR and having multiple coding region differences compared to variant 1 NM_001270485 16 - 4905 NP_001257414 - 588 - 2008 18436530 NM_001270486 16 - 4523 NP_001257415 - 556 - 2008 18436530

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine adrenal gland cortex zona glomerula   highly Homo sapiens   adrenal gland cortex zona fasciculata   lowly Homo sapiens Lymphoid/Immune spleen           thymus         Nervous brain       highly Homo sapiens Reproductive male system testis         male system prostate     highly Respiratory respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Homo sapiens Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol not specific adipocyte Homo sapiens

cell lineage
cell lines	in human non small cell lung cancers
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a catalytic domain
	a regulatory region composed of an autoinhibitory domain
	a CaM binding domain
	AAs 129-151 participate in the release of the autoinhibitory domain from its catalytic core, resulting in generation of autonomous activity
	a flag-tagged protein

HOMOLOGY

interspecies

homolog to rattus Cmkkbeta

Homologene

FAMILY	protein kinase superfamily
	Ser/Thr protein kinase family
	Ca2+/calmodulin-dependent kinase (CaMK) family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	serine/threonine protein kinase, calcium/calmodulin dependent
	acting upstream of AMP-activated protein kinase in mammalian cells
	has potentially a male-specific function in hippocampal memory formation and we have identified male-restricted transcription occurring during hippocampal memory formation
	regulates hypothalamic production of the orexigenic hormone NPY and contributes to the regulation of energy balance
	with STK11, catalyzing activation of PRKAB1 by phosphorylation at Thr172
	act as regulatory enzymes for downstream protein kinases in various Ca2+-dependent cellular processes
	mediates potentially novel Ca2+-signaling pathway(s), which are independent of downstream protein kinases
	isoform-specific function for CAMKK2 that regulates ubiquitin signaling at the centrosome and thereby orchestrates dendrite patterning, with important implications for neuronal connectivity in the brain
	role for CAMKK2 in the restriction of granulocytic fate commitment and differentiation of myeloid progenitor cells
	CAMKK2 and PRKAB1 function in a signaling pathway that participates in the regulation of adiposity
	CaMKK2 plays a pivotal role in the calcium signaling cascade regulating adrenal aldosterone production
	is a molecular rheostat for insulin action
	plays a role in the calcium/calmodulin-dependent kinase cascade
	role for CAMKK2 as a negative regulator of myoblast differentiation and proliferation
	CAMKK2-mediated cell-type-specific differential regulation of mitochondrial function
	CAMKK2 likely sustains cell proliferation in large part through effects on organelle integrity and membrane trafficking
	involved in maintaining various physiological and cellular processes within the cell that regulate energy homeostasis and cell growth
	role of CAMKK2 in Golgi-associated vesicle trafficking
	regulates bone remodeling through its effects on osteoblasts and osteoclasts
	novel CAMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

CAMKK2-PRKAB1 complex that can be specifically targeted by small molecule drugs to treat disease

INTERACTION

DNA

RNA

small molecule

protein	activating CAMK1, CAMK4 when coexpressed in Jurkat T cells
	PACSIN1 is a CAMKK substrate (first non-kinase substrate for CaMKK2)
	CAMKK2 can form a complex with and activate PRKAB1
	important AR-regulated gene in the context of Prostate cancer and as a critical regulator of macrophage activation
	YWHAG directly interacts with the kinase domain of CAMKK2 and the region containing the inhibitory phosphorylation site Thr145 within the N-terminal extension
	a novel role of GPR39 in enhancing tight junction assembly in intestinal epithelial cells (IECs) via phospholipase C-CAMKK2-AMPK pathways
	GEMIN4 is a direct interactor, capable of binding CAMKK2 and COPI subunits
	JMJD1C regulates CAMKK2-AMPK signaling to participate in cardiac hypertrophy

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in gastric cancer and leads to progression tumoral       gain of function in hepatocellular carcinoma (HCC) and negatively correlated with HCC patient survival

Susceptibility

to bipolar and psychiatric disorders

Variant & Polymorphism SNP	Single-Nucleotide Polymorphisms increasing the risk of bipolar and psychiatric disorders

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive   novel therapeutic target for sex hormone-regulated cancers neuromuscular myopathy   CAMKK2 could serve as a potential target to treat patients with muscle injury or myopathies cancer digestive stomach CAMKK2 as a novel therapeutic target in gastric cancer cancer digestive liver CaMKK2 and CaMK4 may represent potential targets for hepatic cancer diabete     CaMKK2 may be an attractive therapeutic target for combatting comorbidities associated with perturbed insulin signaling

ANIMAL & CELL MODELS

CaMKK2 null mice have increased adiposity and larger adipocytes than do wild-type mice, whereas energy balance is unchanged