UniProtKB - Q8TCT0 (CERK1_HUMAN)
Protein
Ceramide kinase
Gene
CERK
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes specifically the phosphorylation of ceramide to form ceramide 1-phosphate (PubMed:11956206, PubMed:16269826, PubMed:19168031). Acts efficiently on natural and analog ceramides (C6, C8, C16 ceramides, and C8-dihydroceramide), to a lesser extent on C2-ceramide and C6-dihydroceramide, but not on other lipids, such as various sphingosines (PubMed:11956206, PubMed:16269826, PubMed:19168031). Shows a greater preference for D-erythro isomer of ceramides (PubMed:16269826). Binds phosphoinositides (PubMed:19168031).3 Publications
Catalytic activityi
- EC:2.7.1.1383 PublicationsThis reaction proceeds in the forward3 Publications direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- ATP + N-hexadecanoylsphing-4-enine = ADP + H+ + N-(hexadecanoyl)-sphing-4-enine-1-phosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- ATP + N-(hexanoyl)-4-hydroxysphinganine = ADP + H+ + N-(hexanoyl)-4-hydroxysphinganine-1-phosphate1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Activity regulationi
Inhibited by sulfatide (PubMed:19168031). Inhibited by sphinganine, sphingenine, and N,N-Dimethylsphingosine (DMS) (PubMed:16269826). Cardiolipin at 0.1 µM significantly increases activity, whereas at concentrations >1 µM has an inhibitory effect (PubMed:27725450).3 Publications
Kineticsi
- KM=187 µM for C8 ceramide1 Publication
- KM=30 µM for C6 ceramide1 Publication
- KM=22 µM for C2 ceramide1 Publication
- KM=400 µM for ATP (in the presence of 3 mM Mg2+)1 Publication
- KM=32 µM for ATP1 Publication
- Vmax=35 nmol/min/mg enzyme for C6 ceramide1 Publication
pH dependencei
Optimum pH is 6.0-7.8.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 197 | Proton donor/acceptorBy similarity | 1 | |
Binding sitei | 202 | ATPPROSITE-ProRule annotation | 1 | |
Binding sitei | 304 | ATPPROSITE-ProRule annotation | 1 | |
Binding sitei | 310 | ATPPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 138 – 140 | ATPPROSITE-ProRule annotation | 3 | |
Nucleotide bindingi | 170 – 174 | ATPPROSITE-ProRule annotation | 5 | |
Nucleotide bindingi | 239 – 241 | ATPPROSITE-ProRule annotation | 3 | |
Nucleotide bindingi | 502 – 504 | ATPPROSITE-ProRule annotation | 3 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- ceramide kinase activity Source: UniProtKB
- dihydroceramide kinase activity Source: UniProtKB-EC
- lipid kinase activity Source: GO_Central
- magnesium ion binding Source: UniProtKB
- NAD+ kinase activity Source: InterPro
GO - Biological processi
- ceramide metabolic process Source: UniProtKB
- glycosphingolipid metabolic process Source: Reactome
- phosphorylation Source: GO_Central
- sphingolipid metabolic process Source: GO_Central
Keywordsi
Molecular function | Kinase, Transferase |
Ligand | ATP-binding, Calcium, Magnesium, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.1.138, 2681 |
PathwayCommonsi | Q8TCT0 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism |
SABIO-RKi | Q8TCT0 |
Chemistry databases
SwissLipidsi | SLP:000001354 |
Names & Taxonomyi
Protein namesi | Recommended name: Ceramide kinase (EC:2.7.1.1383 Publications)Short name: hCERK Alternative name(s): Acylsphingosine kinase Lipid kinase 4 Short name: LK4 |
Gene namesi | Name:CERK Synonyms:KIAA1646 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000100422.13 |
HGNCi | HGNC:19256, CERK |
MIMi | 610307, gene |
neXtProti | NX_Q8TCT0 |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Peripheral membrane protein 1 Publication
Other locations
- Cytoplasm 1 Publication
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 10 | L → A: 99% decrease in catalytic activity but no effect on substrate affinity. 1 Publication | 1 | |
Mutagenesisi | 10 | L → I: 71% decrease in catalytic activity but no effect on substrate affinity. 1 Publication | 1 | |
Mutagenesisi | 340 | S → A: 15% decrease in catalytic activity and decreased stability. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 64781 |
OpenTargetsi | ENSG00000100422 |
PharmGKBi | PA134958321 |
Miscellaneous databases
Pharosi | Q8TCT0, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1764936 |
GuidetoPHARMACOLOGYi | 2473 |
Polymorphism and mutation databases
BioMutai | CERK |
DMDMi | 30172885 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000181354 | 1 – 537 | Ceramide kinaseAdd BLAST | 537 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 340 | Phosphoserine1 Publication | 1 | |
Modified residuei | 408 | Phosphoserine1 Publication | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q8TCT0 |
jPOSTi | Q8TCT0 |
MassIVEi | Q8TCT0 |
MaxQBi | Q8TCT0 |
PaxDbi | Q8TCT0 |
PeptideAtlasi | Q8TCT0 |
PRIDEi | Q8TCT0 |
ProteomicsDBi | 66749 74154 [Q8TCT0-1] |
PTM databases
iPTMneti | Q8TCT0 |
PhosphoSitePlusi | Q8TCT0 |
Expressioni
Tissue specificityi
High level expression in heart, brain, skeletal muscle, kidney and liver; moderate in peripheral blood leukocytes and thymus; very low in spleen, small intestine, placenta and lung.1 Publication
Gene expression databases
Bgeei | ENSG00000100422, Expressed in islet of Langerhans and 223 other tissues |
ExpressionAtlasi | Q8TCT0, baseline and differential |
Genevisiblei | Q8TCT0, HS |
Organism-specific databases
HPAi | ENSG00000100422, Low tissue specificity |
Interactioni
Binary interactionsi
Hide detailsQ8TCT0
Protein-protein interaction databases
BioGRIDi | 122291, 64 interactors |
IntActi | Q8TCT0, 60 interactors |
STRINGi | 9606.ENSP00000216264 |
Chemistry databases
BindingDBi | Q8TCT0 |
Miscellaneous databases
RNActi | Q8TCT0, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 128 – 278 | DAGKcPROSITE-ProRule annotationAdd BLAST | 151 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 125 | Required for binding to sulfatide and phosphoinositides1 PublicationAdd BLAST | 125 | |
Regioni | 1 – 115 | Essential for enzyme activity1 PublicationAdd BLAST | 115 | |
Regioni | 195 – 198 | Substrate bindingBy similarity | 4 |
Phylogenomic databases
eggNOGi | KOG1115, Eukaryota |
GeneTreei | ENSGT00940000156976 |
HOGENOMi | CLU_013399_2_2_1 |
InParanoidi | Q8TCT0 |
OMAi | FYLWHLT |
PhylomeDBi | Q8TCT0 |
TreeFami | TF314514 |
Family and domain databases
Gene3Di | 3.40.50.10330, 1 hit |
InterProi | View protein in InterPro IPR017438, ATP-NAD_kinase_N IPR001206, Diacylglycerol_kinase_cat_dom IPR016064, NAD/diacylglycerol_kinase_sf |
Pfami | View protein in Pfam PF00781, DAGK_cat, 1 hit |
SMARTi | View protein in SMART SM00046, DAGKc, 1 hit |
SUPFAMi | SSF111331, SSF111331, 1 hit |
PROSITEi | View protein in PROSITE PS50146, DAGK, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q8TCT0-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGATGAAEPL QSVLWVKQQR CAVSLEPARA LLRWWRSPGP GAGAPGADAC
60 70 80 90 100
SVPVSEIIAV EETDVHGKHQ GSGKWQKMEK PYAFTVHCVK RARRHRWKWA
110 120 130 140 150
QVTFWCPEEQ LCHLWLQTLR EMLEKLTSRP KHLLVFINPF GGKGQGKRIY
160 170 180 190 200
ERKVAPLFTL ASITTDIIVT EHANQAKETL YEINIDKYDG IVCVGGDGMF
210 220 230 240 250
SEVLHGLIGR TQRSAGVDQN HPRAVLVPSS LRIGIIPAGS TDCVCYSTVG
260 270 280 290 300
TSDAETSALH IVVGDSLAMD VSSVHHNSTL LRYSVSLLGY GFYGDIIKDS
310 320 330 340 350
EKKRWLGLAR YDFSGLKTFL SHHCYEGTVS FLPAQHTVGS PRDRKPCRAG
360 370 380 390 400
CFVCRQSKQQ LEEEQKKALY GLEAAEDVEE WQVVCGKFLA INATNMSCAC
410 420 430 440 450
RRSPRGLSPA AHLGDGSSDL ILIRKCSRFN FLRFLIRHTN QQDQFDFTFV
460 470 480 490 500
EVYRVKKFQF TSKHMEDEDS DLKEGGKKRF GHICSSHPSC CCTVSNSSWN
510 520 530
CDGEVLHSPA IEVRVHCQLV RLFARGIEEN PKPDSHS
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketF8WFD8 | F8WFD8_HUMAN | Ceramide kinase | CERK | 185 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_053685 | 191 | I → V. Corresponds to variant dbSNP:rs16995615Ensembl. | 1 | |
Natural variantiVAR_053686 | 211 | T → M. Corresponds to variant dbSNP:rs9306515Ensembl. | 1 | |
Natural variantiVAR_053687 | 306 | L → F. Corresponds to variant dbSNP:rs13057352Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056944 | 1 – 198 | Missing in isoform 2. 1 PublicationAdd BLAST | 198 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB079066 mRNA Translation: BAC01154.1 AJ457828 mRNA Translation: CAD29884.1 CR456404 mRNA Translation: CAG30290.1 AK291476 mRNA Translation: BAF84165.1 AL096766 Genomic DNA No translation available. AL118516 Genomic DNA No translation available. CH471138 Genomic DNA Translation: EAW73440.1 CH471138 Genomic DNA Translation: EAW73442.1 BC067255 mRNA Translation: AAH67255.1 BC126940 mRNA Translation: AAI26941.1 AB051433 mRNA Translation: BAB33316.1 |
CCDSi | CCDS14077.1 [Q8TCT0-1] |
RefSeqi | NP_073603.2, NM_022766.5 [Q8TCT0-1] |
Genome annotation databases
Ensembli | ENST00000216264; ENSP00000216264; ENSG00000100422 [Q8TCT0-1] |
GeneIDi | 64781 |
KEGGi | hsa:64781 |
UCSCi | uc003bia.4, human [Q8TCT0-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB079066 mRNA Translation: BAC01154.1 AJ457828 mRNA Translation: CAD29884.1 CR456404 mRNA Translation: CAG30290.1 AK291476 mRNA Translation: BAF84165.1 AL096766 Genomic DNA No translation available. AL118516 Genomic DNA No translation available. CH471138 Genomic DNA Translation: EAW73440.1 CH471138 Genomic DNA Translation: EAW73442.1 BC067255 mRNA Translation: AAH67255.1 BC126940 mRNA Translation: AAI26941.1 AB051433 mRNA Translation: BAB33316.1 |
CCDSi | CCDS14077.1 [Q8TCT0-1] |
RefSeqi | NP_073603.2, NM_022766.5 [Q8TCT0-1] |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 122291, 64 interactors |
IntActi | Q8TCT0, 60 interactors |
STRINGi | 9606.ENSP00000216264 |
Chemistry databases
BindingDBi | Q8TCT0 |
ChEMBLi | CHEMBL1764936 |
GuidetoPHARMACOLOGYi | 2473 |
SwissLipidsi | SLP:000001354 |
PTM databases
iPTMneti | Q8TCT0 |
PhosphoSitePlusi | Q8TCT0 |
Polymorphism and mutation databases
BioMutai | CERK |
DMDMi | 30172885 |
Proteomic databases
EPDi | Q8TCT0 |
jPOSTi | Q8TCT0 |
MassIVEi | Q8TCT0 |
MaxQBi | Q8TCT0 |
PaxDbi | Q8TCT0 |
PeptideAtlasi | Q8TCT0 |
PRIDEi | Q8TCT0 |
ProteomicsDBi | 66749 74154 [Q8TCT0-1] |
Protocols and materials databases
Antibodypediai | 326, 310 antibodies |
DNASUi | 64781 |
Genome annotation databases
Ensembli | ENST00000216264; ENSP00000216264; ENSG00000100422 [Q8TCT0-1] |
GeneIDi | 64781 |
KEGGi | hsa:64781 |
UCSCi | uc003bia.4, human [Q8TCT0-1] |
Organism-specific databases
CTDi | 64781 |
DisGeNETi | 64781 |
EuPathDBi | HostDB:ENSG00000100422.13 |
GeneCardsi | CERK |
HGNCi | HGNC:19256, CERK |
HPAi | ENSG00000100422, Low tissue specificity |
MIMi | 610307, gene |
neXtProti | NX_Q8TCT0 |
OpenTargetsi | ENSG00000100422 |
PharmGKBi | PA134958321 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1115, Eukaryota |
GeneTreei | ENSGT00940000156976 |
HOGENOMi | CLU_013399_2_2_1 |
InParanoidi | Q8TCT0 |
OMAi | FYLWHLT |
PhylomeDBi | Q8TCT0 |
TreeFami | TF314514 |
Enzyme and pathway databases
BRENDAi | 2.7.1.138, 2681 |
PathwayCommonsi | Q8TCT0 |
Reactomei | R-HSA-1660662, Glycosphingolipid metabolism |
SABIO-RKi | Q8TCT0 |
Miscellaneous databases
BioGRID-ORCSi | 64781, 3 hits in 849 CRISPR screens |
ChiTaRSi | CERK, human |
GeneWikii | CERK |
GenomeRNAii | 64781 |
Pharosi | Q8TCT0, Tchem |
PROi | PR:Q8TCT0 |
RNActi | Q8TCT0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000100422, Expressed in islet of Langerhans and 223 other tissues |
ExpressionAtlasi | Q8TCT0, baseline and differential |
Genevisiblei | Q8TCT0, HS |
Family and domain databases
Gene3Di | 3.40.50.10330, 1 hit |
InterProi | View protein in InterPro IPR017438, ATP-NAD_kinase_N IPR001206, Diacylglycerol_kinase_cat_dom IPR016064, NAD/diacylglycerol_kinase_sf |
Pfami | View protein in Pfam PF00781, DAGK_cat, 1 hit |
SMARTi | View protein in SMART SM00046, DAGKc, 1 hit |
SUPFAMi | SSF111331, SSF111331, 1 hit |
PROSITEi | View protein in PROSITE PS50146, DAGK, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CERK1_HUMAN | |
Accessioni | Q8TCT0Primary (citable) accession number: Q8TCT0 Secondary accession number(s): A0JNT4 Q9UGE5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 23, 2003 |
Last sequence update: | June 1, 2002 | |
Last modified: | December 2, 2020 | |
This is version 160 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations