CLK1 CDC like kinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CLK1provided by HGNC
Official Full Name: CDC like kinase 1provided by HGNC
Primary source: HGNC:HGNC:2068
See related: Ensembl:ENSG00000013441 MIM:601951; AllianceGenome:HGNC:2068
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: CLK; STY; CLK/STY
Summary: This gene encodes a member of the CDC2-like (or LAMMER) family of dual specificity protein kinases. In the nucleus, the encoded protein phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing, releasing them into the nucleoplasm. The choice of splice sites during pre-mRNA processing may be regulated by the concentration of transacting factors, including serine/arginine rich proteins. Therefore, the encoded protein may play an indirect role in governing splice site selection. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]
Expression: Ubiquitous expression in bone marrow (RPKM 96.5), lymph node (RPKM 51.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q33.1

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (200853009..200864658, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (201336455..201348106, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (201717732..201729381, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.
Title: Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.
CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly.
Title: CLK1 reorganizes the splicing factor U1-70K for early spliceosomal protein assembly.
Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer.
Title: Phosphoproteomic analysis identifies CLK1 as a novel therapeutic target in gastric cancer.
A conserved sequence motif bridges two protein kinases for enhanced phosphorylation and nuclear function of a splicing factor.
Title: A conserved sequence motif bridges two protein kinases for enhanced phosphorylation and nuclear function of a splicing factor.
LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation.
Title: LncRNA-dependent nuclear stress bodies promote intron retention through SR protein phosphorylation.
found that CLK1 amplifies its presence in the nucleus by forming a stable complex with the Ser-Arg protein substrate
Title: Disordered protein interactions for an ordered cellular transition: Cdc2-like kinase 1 is transported to the nucleus via its Ser-Arg protein substrate.
We now show that the ability of SRPK1 to mobilize SRSF1 from speckles to the nucleoplasm is dependent on active CLK1. Diffusion from speckles is promoted by the formation of an SRPK1-CLK1 complex that facilitates dissociation of SRSF1 from CLK1 and enhances the phosphorylation of several serine-proline dipeptides in this SR protein
Title: Mobilization of a splicing factor through a nuclear kinase-kinase complex.
Data suggest that CLK1 activity in both transformed and normal cells is carefully regulated via CLK1 alternative splicing through both exon 4 skipping and intron 4 retention. CLK1 autoregulates by favoring the expression of truncated isoforms, CLK1T1 and CLKT2 in environmental stress.
Title: Autoregulation of the human splice factor kinase CLK1 through exon skipping and intron retention.
These results thus reveal a large program of CLK1-regulated periodic alternative splicing intimately associated with cell cycle control.
Title: An extensive program of periodic alternative splicing linked to cell cycle progression.
Global CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor has been described.
Title: CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor.

Submit: New GeneRIF Correction See all GeneRIFs (23)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S1423 (e-PCR)
- UniSTS:149619

RH80225 (e-PCR)
- UniSTS:88691

RH80114 (e-PCR)
- UniSTS:91271

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables non-membrane spanning protein tyrosine kinase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction 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 serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine/tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in regulation of RNA splicing	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of RNA splicing	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: dual specificity protein kinase CLK1

Names: CDC28/CDC2-like kinase; protein tyrosine kinase STY

NP_001155879.1

EC 2.7.12.1

NP_004062.2

EC 2.7.12.1

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)

NM_001162407.1 → NP_001155879.1 dual specificity protein kinase CLK1 isoform 2

See identical proteins and their annotated locations for NP_001155879.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site and upstream start codon, compared to variant 1. The resulting isoform (2) has a longer N-terminus, compared to isoform 1.

Source sequence(s)

AI251890, AK294295

Consensus CDS

CCDS54427.1

UniProtKB/TrEMBL

B7ZA12

Related

ENSP00000394734.2, ENST00000434813.3

Conserved Domains (2) summary

smart00220
Location:203 → 519

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14213
Location:190 → 519

PKc_CLK1_4; Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4
NM_004071.4 → NP_004062.2 dual specificity protein kinase CLK1 isoform 1

See identical proteins and their annotated locations for NP_004062.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the shorter isoform (1).

Source sequence(s)

AI251890, BC031549, DA225472

Consensus CDS

CCDS2331.1

UniProtKB/Swiss-Prot

B4DFW7, P49759, Q0P694, Q8N5V8

UniProtKB/TrEMBL

B7ZA12

Related

ENSP00000326830.4, ENST00000321356.9

Conserved Domains (1) summary

cd14213
Location:148 → 477

PKc_CLK1_4; Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4

RNA

NR_027855.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AI251890, BC028149, DA225472

Related

ENST00000432425.5
NR_027856.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (4) retains several introns, compared to variant 1. The transcript is sufficiently abundant to represent as a RefSeq record; however, the variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AI251890, BC028573, DA225472, DB164846

Related

ENST00000473565.5

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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

200853009..200864658 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

201336455..201348106 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001024646.1: Suppressed sequence

Description

NM_001024646.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.