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FLASH GENE

Symbol

DCLK1

contributors: mct/npt - updated : 25-01-2023

HGNC name	doublecortin-like kinase 1
HGNC id	2700

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

text	type A (AS and AL) and type B (BS and BL) isoforms differ respectively by the presence or absence of the doublecortin domain an alternative splicing occurring in 3' of the mRNA produces the long (L) instead of the short (S) isoforms

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001195415 14 splicing 7592 NP_001182344 - 422 DCLK1-short-A is relatively more strongly expressed than DCLK1-short-B in the subependymal zone 2004 14741399 variant 1 - A short DCLK1-short-A and -B control different neuronal processes that overlap with those controlled by CaMKs NM_004734 18 splicing 8453 NP_004725 81 729 - 2004 14741399 variant 2 - A long NM_001195430 3 splicing 5342 NP_001182359 - 56 . DCLK1-short-B variant shows stronger expression in the cortex, the ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus, the zona incerta and the subincertal nucleus 2004 14741399 variant 3 - B short DCLK1-short-A and -B control different neuronal processes that overlap with those controlled by CaMKs NM_001195416 13 splicing 7518 NP_001182345 47.6 433 adult, fetal brain 2004 14741399 variant 4 - B long

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 Cardiovascular heart         Digestive intestine large intestine colon     Homo sapiens   stomach         Homo sapiens Endocrine neuroendocrine pituitary     predominantly Hearing/Equilibrium ear inner     highly Homo sapiens Lymphoid/Immune spleen       moderately   thymus         Nervous brain       predominantly Homo sapiens   nerve       predominantly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     moderately Epithelial absorptive excretory digestive epithelium (mucosa)     Homo sapiens Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Digestive epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	brain, lung, liver

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	an N terminal region homologous to DCX (doublecortin) and to a rat Ca2+/calmodulin dependent kinase CPG16 at C terminus
	two doublecortin domains
	C-terminal serine/threonine kinase domain

HOMOLOGY

interspecies

ortholog to murine Dcamkl1 (98.4pc)

intraspecies	homolog to calcium/calmodulin-dependent protein kinase 1
	paralog to DCX

Homologene

FAMILY	Ser/Thr protein kinase family
	CaMK subfamily
	family of microtubule-associated proteins
	neuronal microtubule-associated doublecortin (DCX) family

CATEGORY

signaling , receptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus
text	localized in mitotic cells, radial glial cells and radial processes
	the kinase fragment of DCLK1 is translocated into the nucleus upon hyperosmotic stresses and the kinase efficiently phosphorylates JDP2, a possible target in the nucleus, with the aid of histones
	in human intestinal epithelium, DLCK1-positive cells form a subpopulation of non-proliferating neuroendocrine cells with apical brush border similar to that in enterocytes

basic FUNCTION	participating in functions of the mature nervous system
	involved in a calcium-signaling pathway controlling neuronal migration in the developing brain
	acting as a protein serine/threonine kinase
	acting as a receptor signaling protein
	may have a role in migrating neurons
	critically involved in dynamic rearrangement of the cytoskeletal machinery that allow migration
	playing a unique role in mitotic spindle integrity during early neurogenesis in radial glial cell proliferation and their radial process stability
	is a functionally pertinent gene involved in human memory and cognitive functions
	unique roles for DCLK1 in adult neurogenesis
	role for DCX and DCLK1 in enabling microtubules to overcome retrograde actin-based forces, thereby facilitating the ability of the growth cone to carry out its crucial path-finding functions
	is a physiologically relevant regulator of anabolic bone formation
	CDH13, GRM8, ANK2, SLC16A6, ARSG, RIMBP2 and DCLK1 having role in hearing function
	importance of DCLK1 function in tumorigenesis and cancer (PMIDC:
	functions in multiple stages of neural development including radial migration and axon growth of cortical neurons
	DCLK1 kinase activity negatively regulates microtubule polymerization
	is a microtubule-associated kinase
	tuft cells, via DCLK1, are important responders to bacterial-induced colitis by enhancing epithelial repair responses, which in turn limits bacterial infiltration into the mucosa
	DCLK1 autophosphorylates a residue within its C-terminal tail to restrict its kinase activity and prevent aberrant hyperphosphorylation within its microtubule-binding domain
	DCLK1 modulates likely its kinase activity to tune its microtubule-binding affinity
	roles of DCLK1 in augmenting SARS-CoV-2 viremia, inflammatory cytokine expression, and dysregulation of immune cells involved in innate immunity
	DCLK1 regulates tumorigenesis and epithelial&
	8209;mesenchymal transformation via several important pathways, such as NOTCH1, WNT/CTNNB1, RAS and multiple microRNAs

CELLULAR PROCESS	cell life, differentiation

PHYSIOLOGICAL PROCESS

development , nervous system , cellular trafficking transport

text	central nervous system development
	endosome transport

PATHWAY

metabolism

signaling

signal transduction

intracellular signaling cascade

a component

INTERACTION

DNA

RNA

small molecule	nucleotide,
	ATP

protein	DCX to form a potentially mutually regulatory network linking calcium signaling and microtubule dynamics
	represses osteoblast activation by antagonizing RUNX2, the master transcription factor in osteoblasts
	guides KIF1A-mediated cargo transport to dendrites
	MAP7D1 is a novel substrate of DCLK1, and DCLK1 phosphorylates MAP7D1 on Ser 315 to facilitate axon elongation of cortical neurons

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in many cancers including colorectal cancer (CRC) tumoral     --over   may be responsible for the increased metastatic features in breast cancer cells

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	DCLK1 may serve as an independent predictor for Colo-rectal cancer prognosis
	evaluating high serum DCLK1 is a biomarker for detection of hepatocellular carcinoma (HCC)
Therapy target
	System Type Disorder Pubmed cancer digestive liver therapeutic target for eradicating HCC cancer digestive colon potential therapeutic target for the treatment of colorectal cancer cancer brain glioma/neuroblstoma silencing DCLK1 induces apoptosis in NB cells cancer digestive colon potential for developing a therapy for colorectal cancer based on targeting DCLK1-positive tumor stem cells (TSCs) cancer     potential anti‑tumor target via the glucose metabolism pathway immunology infectious   DCLK1 could be a potential therapeutic target for COVID-19, especially in patients with underlying comorbid diseases associated with DCLK1 expression cancer reproductive breast targeting DCLK1 may become a therapeutic option for breast cancer metastasis

ANIMAL & CELL MODELS

mice with a targeted disruption of Dcamkl1 displayed elevated bone mass secondary to increased bone formation by osteoblasts