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DCLK1 doublecortin like kinase 1 [ Homo sapiens (human) ]

Gene ID: 9201, updated on 7-Apr-2024

Summary

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Official Symbol
DCLK1provided by HGNC
Official Full Name
doublecortin like kinase 1provided by HGNC
Primary source
HGNC:HGNC:2700
See related
Ensembl:ENSG00000133083 MIM:604742; AllianceGenome:HGNC:2700
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
CL1; DCLK; CLICK1; DCDC3A; DCAMKL1
Summary
This gene encodes a member of the protein kinase superfamily and the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, a C-terminal serine/threonine protein kinase domain, which shows substantial homology to Ca2+/calmodulin-dependent protein kinase, and a serine/proline-rich domain in between the doublecortin and the protein kinase domains, which mediates multiple protein-protein interactions. The microtubule-polymerizing activity of the encoded protein is independent of its protein kinase activity. The encoded protein is involved in several different cellular processes, including neuronal migration, retrograde transport, neuronal apoptosis and neurogenesis. This gene is up-regulated by brain-derived neurotrophic factor and associated with memory and general cognitive abilities. Multiple transcript variants generated by two alternative promoter usage and alternative splicing have been reported, but the full-length nature and biological validity of some variants have not been defined. These variants encode different isoforms, which are differentially expressed and have different kinase activities.[provided by RefSeq, Sep 2010]
Expression
Biased expression in brain (RPKM 28.5), fat (RPKM 4.0) and 7 other tissues See more
Orthologs
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Genomic context

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Location:
13q13.3
Exon count:
21
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (35768652..36131939, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (34986929..35351445, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (36342789..36706076, complement)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903224 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:36270618-36271214 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:36271215-36271810 Neighboring gene NANOG hESC enhancer GRCh37_chr13:36286938-36287653 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:36294554-36295054 Neighboring gene long intergenic non-protein coding RNA 445 Neighboring gene NANOG hESC enhancer GRCh37_chr13:36363862-36364363 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr13:36429462-36430661 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:36431613-36432152 Neighboring gene uncharacterized LOC105370163 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:36432695-36433234 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr13:36466409-36467608 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:36490885-36491627 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:36496595-36497587 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7587 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7588 Neighboring gene NANOG hESC enhancer GRCh37_chr13:36567619-36568120 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr13:36587826-36589025 Neighboring gene nuclear-encoded mitochondrial tRNA-Gln (TTG) 10-1 Neighboring gene CCDC169-SOHLH2 readthrough Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:36728605-36729169 Neighboring gene uncharacterized LOC107984604 Neighboring gene MPRA-validated peak2068 silencer Neighboring gene spermatogenesis and oogenesis specific basic helix-loop-helix 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling. Liu H, et al. Breast Cancer Res, 2023 Apr 17. PMID 37069669, Free PMC Article
  2. Doublecortin-like kinase 1 is a therapeutic target in squamous cell carcinoma. Standing D, et al. Mol Carcinog, 2023 Feb. PMID 36218231, Free PMC Article
  3. Targeting DCLK1 overcomes 5-fluorouracil resistance in colorectal cancer through inhibiting CCAR1/β-catenin pathway-mediated cancer stemness. Wang L, et al. Clin Transl Med, 2022 May. PMID 35522902, Free PMC Article
  4. DCLK1 might be a therapeutic target of osthole against cervical cancer. Pan L, et al. Pharmazie, 2021 Oct 1. PMID 34620279
  5. Structural basis for small molecule targeting of Doublecortin Like Kinase 1 with DCLK1-IN-1. Patel O, et al. Commun Biol, 2021 Sep 20. PMID 34545159, Free PMC Article

See all (143) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. DCLK1 and its oncogenic functions: A promising therapeutic target for cancers.
    Title: DCLK1 and its oncogenic functions: A promising therapeutic target for cancers.
  2. Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome.
    Title: Role of DCLK1/Hippo pathway in type II alveolar epithelial cells differentiation in acute respiratory distress syndrome.
  3. Exosomes from metastatic colon cancer cells drive the proliferation and migration of primary colon cancer through increased expression of cancer stem cell markers CD133 and DCLK1.
    Title: Exosomes from metastatic colon cancer cells drive the proliferation and migration of primary colon cancer through increased expression of cancer stem cell markers CD133 and DCLK1.
  4. [Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells].
    Title: [Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells].
  5. Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling.
    Title: Targeting DCLK1 attenuates tumor stemness and evokes antitumor immunity in triple-negative breast cancer by inhibiting IL-6/STAT3 signaling.
  6. Doublecortin-like kinase 1 is a therapeutic target in squamous cell carcinoma.
    Title: Doublecortin-like kinase 1 is a therapeutic target in squamous cell carcinoma.
  7. KDM3A promotes oral squamous cell carcinoma cell proliferation and invasion via H3K9me2 demethylation-activated DCLK1.
    Title: KDM3A promotes oral squamous cell carcinoma cell proliferation and invasion via H3K9me2 demethylation-activated DCLK1.
  8. Targeting Doublecortin-Like Kinase 1 (DCLK1)-Regulated SARS-CoV-2 Pathogenesis in COVID-19.
    Title: Targeting Doublecortin-Like Kinase 1 (DCLK1)-Regulated SARS-CoV-2 Pathogenesis in COVID-19.
  9. DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis.
    Title: DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis.
  10. Targeting DCLK1 overcomes 5-fluorouracil resistance in colorectal cancer through inhibiting CCAR1/beta-catenin pathway-mediated cancer stemness.
    Title: Targeting DCLK1 overcomes 5-fluorouracil resistance in colorectal cancer through inhibiting CCAR1/β-catenin pathway-mediated cancer stemness.
Submit: New GeneRIF Correction See all GeneRIFs (96)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study of optic disc parameters.
EBI GWAS Catalog
Genetic variants associated with breast size also influence breast cancer risk.
EBI GWAS Catalog
Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study.
EBI GWAS Catalog
Genome-wide association study of the age of onset of childhood asthma.
EBI GWAS Catalog
Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan.
EBI GWAS Catalog
Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry.
EBI GWAS Catalog
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0369

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity 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 IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in axon extension IEA
Inferred from Electronic Annotation
more info
  
involved_in central nervous system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in central nervous system projection neuron axonogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in dendrite morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in endosomal transport NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in forebrain development IEA
Inferred from Electronic Annotation
more info
  
involved_in intracellular signal transduction IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of protein localization to nucleus IEA
Inferred from Electronic Annotation
more info
  
involved_in nervous system development TAS
Traceable Author Statement
more info
 PubMed 
involved_in neuron migration IEA
Inferred from Electronic Annotation
more info
  
involved_in neuron projection morphogenesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein localization to nucleus IEA
Inferred from Electronic Annotation
more info
  
involved_in protein phosphorylation TAS
Traceable Author Statement
more info
 PubMed 
involved_in response to virus IEP
Inferred from Expression Pattern
more info
 PubMed 
Component Evidence Code Pubs
located_in plasma membrane TAS
Traceable Author Statement
more info
 PubMed 
located_in postsynaptic density IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
serine/threonine-protein kinase DCLK1
Names
doublecortin domain-containing protein 3A
doublecortin-like and CAM kinase-like 1
NP_001182344.1
NP_001182345.1
NP_001182359.1
NP_001317000.1
NP_001317001.1
NP_004725.1
XP_016876336.1
XP_016876337.1
XP_047286723.1
XP_054231145.1
XP_054231146.1
XP_054231147.1

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

  1. NM_001195415.2 → NP_001182344.1  serine/threonine-protein kinase DCLK1 isoform 2

    See identical proteins and their annotated locations for NP_001182344.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also known as DCLK-short-B, DCK-beta1 or KIAA0369-BS) is produced from the 3' promoter. It lacks several 5' exons but has an alternate 5' exon, as compared to variant 1. The resulting isoform (2) has a shorter and different N-terminus, and lacks doublecortin domains, as compared to isoform 1.
    Source sequence(s)
    AK295777, AL139083, AL157760
    Consensus CDS
    CCDS73561.1
    UniProtKB/TrEMBL
    B7Z5K4
    Related
    ENSP00000484452.1, ENST00000615680.5
    Conserved Domains (1) summary
    cd14183
    Location:76 → 343
    STKc_DCKL1; Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1)

  2. NM_001195416.2 → NP_001182345.1  serine/threonine-protein kinase DCLK1 isoform 3

    See identical proteins and their annotated locations for NP_001182345.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant [3, also known as DCLK-short-A, DCK-beta2, KIAA0369-BL or cpg16 (candidate plasticity gene 16)] is produced from the 3' promoter. It lacks several 5' exons but has an alternate 5' exon, and lacks a coding exon in the 3' region that results in a frame-shift, as compared to variant 1. The resulting isoform (3) has a shorter and different N-terminus and a longer and distinct C-terminus, and lacks doublecortin domains, as compared to isoform 1.
    Source sequence(s)
    AK299059, AK311195, AL139083, AL157760, BC152456
    Consensus CDS
    CCDS55895.1
    UniProtKB/TrEMBL
    B7Z5K4
    Related
    ENSP00000369223.1, ENST00000379893.5
    Conserved Domains (1) summary
    cd14183
    Location:76 → 343
    STKc_DCKL1; Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1)

  3. NM_001195430.2 → NP_001182359.1  serine/threonine-protein kinase DCLK1 isoform 4

    See identical proteins and their annotated locations for NP_001182359.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) is produced from the 3' promoter. It shares only one exon with variant 1, and encodes a 56 aa long isoform [4, also known as ania-4, or CARP (CaMK-related peptide)], which mainly consists of the serine/proline-rich domain.
    Source sequence(s)
    AL157760, BM682165
    UniProtKB/TrEMBL
    A0A9L9PXT2
    Related
    ENSP00000516676.1, ENST00000460982.1

  4. NM_001330071.2 → NP_001317000.1  serine/threonine-protein kinase DCLK1 isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks an alternate exon in the 3' coding region, resulting in a frameshift compared to variant 1. Both variants 5 and 6 encode the same isoform (5), which is longer and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AK295777, AL139083, AL157760, AL160392, BC152456, BM679448, DB453639, DC350316, HY138649
    Consensus CDS
    CCDS81762.1
    UniProtKB/Swiss-Prot
    B7Z3E9, O15075, Q5VZY8, Q5VZZ0, Q5VZZ1
    UniProtKB/TrEMBL
    B7Z2T7
    Related
    ENSP00000353846.3, ENST00000360631.8
    Conserved Domains (3) summary
    cd14183
    Location:383 → 650
    STKc_DCKL1; Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1)
    cd17069
    Location:182 → 265
    DCX2; Dublecortin-like domain 2
    cd17140
    Location:55 → 143
    DCX1_DCLK1; Dublecortin-like domain 1 found in doublecortin-like kinase 1 (DCLK1)

  5. NM_001330072.2 → NP_001317001.1  serine/threonine-protein kinase DCLK1 isoform 5

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR and lacks an alternate exon in the 3' coding region, resulting in a frameshift compared to variant 1. Both variants 5 and 6 encode the same isoform (5), which is longer and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AK295777, AL139083, AL157760, BC152456, BM679448, DA154341, DC350316
    Consensus CDS
    CCDS81762.1
    UniProtKB/Swiss-Prot
    B7Z3E9, O15075, Q5VZY8, Q5VZZ0, Q5VZZ1
    UniProtKB/TrEMBL
    B7Z2T7
    Conserved Domains (3) summary
    cd14183
    Location:383 → 650
    STKc_DCKL1; Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1)
    cd17069
    Location:182 → 265
    DCX2; Dublecortin-like domain 2
    cd17140
    Location:55 → 143
    DCX1_DCLK1; Dublecortin-like domain 1 found in doublecortin-like kinase 1 (DCLK1)

  6. NM_004734.5 → NP_004725.1  serine/threonine-protein kinase DCLK1 isoform 1

    See identical proteins and their annotated locations for NP_004725.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1, also known as DCLK-long-B, DCK-alpha1 or KIAA0369AS) is produced from the 5' promoter. It encodes the isoform 1, which includes two doublecortin domains, a serine/proline-rich domain and a protein kinase domain.
    Source sequence(s)
    AK295777, AL139083, AL157760, AL160392, BC152456
    Consensus CDS
    CCDS9354.1
    UniProtKB/TrEMBL
    B7Z2T7
    Related
    ENSP00000255448.4, ENST00000255448.8
    Conserved Domains (3) summary
    cd14183
    Location:383 → 650
    STKc_DCKL1; Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1)
    cd17069
    Location:182 → 265
    DCX2; Dublecortin-like domain 2
    cd17140
    Location:55 → 143
    DCX1_DCLK1; Dublecortin-like domain 1 found in doublecortin-like kinase 1 (DCLK1)

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_000013.11 Reference GRCh38.p14 Primary Assembly

    Range
    35768652..36131939 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017020847.2 → XP_016876336.1  serine/threonine-protein kinase DCLK1 isoform X1

    UniProtKB/TrEMBL
    B7Z2T7
    Conserved Domains (3) summary
    cd14183
    Location:383 → 650
    STKc_DCKL1; Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1)
    cd17069
    Location:182 → 265
    DCX2; Dublecortin-like domain 2
    cd17140
    Location:55 → 143
    DCX1_DCLK1; Dublecortin-like domain 1 found in doublecortin-like kinase 1 (DCLK1)

  2. XM_047430767.1 → XP_047286723.1  serine/threonine-protein kinase DCLK1 isoform X2

    UniProtKB/TrEMBL
    Q5VZY9

  3. XM_017020848.2 → XP_016876337.1  serine/threonine-protein kinase DCLK1 isoform X2

    UniProtKB/TrEMBL
    Q5VZY9
    Related
    ENSP00000369222.4, ENST00000379892.4
    Conserved Domains (2) summary
    cd17069
    Location:182 → 265
    DCX2; Dublecortin-like domain 2
    cd17140
    Location:55 → 143
    DCX1_DCLK1; Dublecortin-like domain 1 found in doublecortin-like kinase 1 (DCLK1)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060937.1 Alternate T2T-CHM13v2.0

    Range
    34986929..35351445 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054375170.1 → XP_054231145.1  serine/threonine-protein kinase DCLK1 isoform X1

  2. XM_054375172.1 → XP_054231147.1  serine/threonine-protein kinase DCLK1 isoform X2

    UniProtKB/TrEMBL
    Q5VZY9

  3. XM_054375171.1 → XP_054231146.1  serine/threonine-protein kinase DCLK1 isoform X2

    UniProtKB/TrEMBL
    Q5VZY9
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O15075.2 GenPept UniProtKB/Swiss-Prot:O15075

Gene LinkOut

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