Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ceramide kinase

Gene

CERK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes specifically the phosphorylation of ceramide to form ceramide 1-phosphate. 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. Binds phosphoinositides.1 Publication

Catalytic activityi

ATP + ceramide = ADP + ceramide 1-phosphate.

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Inhibited by sulfatide.1 Publication

pH dependencei

Optimum pH is 6.0-7.5.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei197Proton donor/acceptorBy similarity1
Binding sitei202ATPPROSITE-ProRule annotation1
Binding sitei304ATPPROSITE-ProRule annotation1
Binding sitei310ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi138 – 140ATPPROSITE-ProRule annotation3
Nucleotide bindingi170 – 174ATPPROSITE-ProRule annotation5
Nucleotide bindingi239 – 241ATPPROSITE-ProRule annotation3
Nucleotide bindingi502 – 504ATPPROSITE-ProRule annotation3

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • ceramide kinase activity Source: UniProtKB
  • magnesium ion binding Source: UniProtKB

GO - Biological processi

  • ceramide metabolic process Source: UniProtKB
  • glycosphingolipid metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Calcium, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS02080-MONOMER.
BRENDAi2.7.1.138. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
SABIO-RKQ8TCT0.

Chemistry databases

SwissLipidsiSLP:000001354.

Names & Taxonomyi

Protein namesi
Recommended name:
Ceramide kinase (EC:2.7.1.138)
Short name:
hCERK
Alternative name(s):
Acylsphingosine kinase
Lipid kinase 4
Short name:
LK4
Gene namesi
Name:CERK
Synonyms:KIAA1646
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:19256. CERK.

Subcellular locationi

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB
  • mitochondrion Source: Ensembl
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi10L → A: 99% decrease in catalytic activity but no effect on substrate affinity. 1 Publication1
Mutagenesisi10L → I: 71% decrease in catalytic activity but no effect on substrate affinity. 1 Publication1
Mutagenesisi340S → A: 15% decrease in catalytic activity and decreased stability. 1 Publication1

Organism-specific databases

DisGeNETi64781.
OpenTargetsiENSG00000100422.
PharmGKBiPA134958321.

Chemistry databases

ChEMBLiCHEMBL1764936.
GuidetoPHARMACOLOGYi2473.

Polymorphism and mutation databases

BioMutaiCERK.
DMDMi30172885.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001813541 – 537Ceramide kinaseAdd BLAST537

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei340Phosphoserine1 Publication1
Modified residuei408Phosphoserine1 Publication1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8TCT0.
MaxQBiQ8TCT0.
PaxDbiQ8TCT0.
PeptideAtlasiQ8TCT0.
PRIDEiQ8TCT0.

PTM databases

iPTMnetiQ8TCT0.
PhosphoSitePlusiQ8TCT0.

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.

Gene expression databases

BgeeiENSG00000100422.
CleanExiHS_CERK.
ExpressionAtlasiQ8TCT0. baseline and differential.
GenevisibleiQ8TCT0. HS.

Organism-specific databases

HPAiHPA014700.
HPA064699.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ALAS1P131963EBI-10274247,EBI-3905054
MTUS2Q5JR593EBI-10274247,EBI-742948
NOTCH2NLQ7Z3S93EBI-10274247,EBI-945833

Protein-protein interaction databases

BioGridi122291. 45 interactors.
IntActiQ8TCT0. 33 interactors.
STRINGi9606.ENSP00000216264.

Chemistry databases

BindingDBiQ8TCT0.

Structurei

3D structure databases

ProteinModelPortaliQ8TCT0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini128 – 278DAGKcPROSITE-ProRule annotationAdd BLAST151

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 125Required for binding to sulfatide and phosphoinositidesAdd BLAST125
Regioni195 – 198Substrate bindingBy similarity4

Sequence similaritiesi

Contains 1 DAGKc domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1115. Eukaryota.
COG1597. LUCA.
GeneTreeiENSGT00690000101761.
HOGENOMiHOG000111551.
HOVERGENiHBG050903.
InParanoidiQ8TCT0.
KOiK04715.
OMAiNYAMRLS.
OrthoDBiEOG091G0FFW.
PhylomeDBiQ8TCT0.
TreeFamiTF314514.

Family and domain databases

InterProiIPR001206. Diacylglycerol_kinase_cat_dom.
IPR016064. NAD/diacylglycerol_kinase.
[Graphical view]
PfamiPF00781. DAGK_cat. 1 hit.
[Graphical view]
SMARTiSM00046. DAGKc. 1 hit.
[Graphical view]
SUPFAMiSSF111331. SSF111331. 3 hits.
PROSITEiPS50146. DAGK. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TCT0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:537
Mass (Da):59,977
Last modified:June 1, 2002 - v1
Checksum:i3DBFC0ED8D679F7F
GO
Isoform 2 (identifier: Q8TCT0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-198: Missing.

Note: No experimental confirmation available.
Show »
Length:339
Mass (Da):37,781
Checksum:iA4C2ACDFF2E6F3D0
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053685191I → V.Corresponds to variant rs16995615dbSNPEnsembl.1
Natural variantiVAR_053686211T → M.Corresponds to variant rs9306515dbSNPEnsembl.1
Natural variantiVAR_053687306L → F.Corresponds to variant rs13057352dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0569441 – 198Missing in isoform 2. 1 PublicationAdd BLAST198

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, AL118516 Genomic DNA. Translation: CAI18819.1.
AL118516, AL096766 Genomic DNA. Translation: CAI17953.1.
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.
CCDSiCCDS14077.1. [Q8TCT0-1]
RefSeqiNP_073603.2. NM_022766.5. [Q8TCT0-1]
UniGeneiHs.200668.

Genome annotation databases

EnsembliENST00000216264; ENSP00000216264; ENSG00000100422. [Q8TCT0-1]
GeneIDi64781.
KEGGihsa:64781.
UCSCiuc003bia.4. human. [Q8TCT0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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, AL118516 Genomic DNA. Translation: CAI18819.1.
AL118516, AL096766 Genomic DNA. Translation: CAI17953.1.
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.
CCDSiCCDS14077.1. [Q8TCT0-1]
RefSeqiNP_073603.2. NM_022766.5. [Q8TCT0-1]
UniGeneiHs.200668.

3D structure databases

ProteinModelPortaliQ8TCT0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122291. 45 interactors.
IntActiQ8TCT0. 33 interactors.
STRINGi9606.ENSP00000216264.

Chemistry databases

BindingDBiQ8TCT0.
ChEMBLiCHEMBL1764936.
GuidetoPHARMACOLOGYi2473.
SwissLipidsiSLP:000001354.

PTM databases

iPTMnetiQ8TCT0.
PhosphoSitePlusiQ8TCT0.

Polymorphism and mutation databases

BioMutaiCERK.
DMDMi30172885.

Proteomic databases

EPDiQ8TCT0.
MaxQBiQ8TCT0.
PaxDbiQ8TCT0.
PeptideAtlasiQ8TCT0.
PRIDEiQ8TCT0.

Protocols and materials databases

DNASUi64781.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216264; ENSP00000216264; ENSG00000100422. [Q8TCT0-1]
GeneIDi64781.
KEGGihsa:64781.
UCSCiuc003bia.4. human. [Q8TCT0-1]

Organism-specific databases

CTDi64781.
DisGeNETi64781.
GeneCardsiCERK.
HGNCiHGNC:19256. CERK.
HPAiHPA014700.
HPA064699.
MIMi610307. gene.
neXtProtiNX_Q8TCT0.
OpenTargetsiENSG00000100422.
PharmGKBiPA134958321.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1115. Eukaryota.
COG1597. LUCA.
GeneTreeiENSGT00690000101761.
HOGENOMiHOG000111551.
HOVERGENiHBG050903.
InParanoidiQ8TCT0.
KOiK04715.
OMAiNYAMRLS.
OrthoDBiEOG091G0FFW.
PhylomeDBiQ8TCT0.
TreeFamiTF314514.

Enzyme and pathway databases

BioCyciZFISH:HS02080-MONOMER.
BRENDAi2.7.1.138. 2681.
ReactomeiR-HSA-1660662. Glycosphingolipid metabolism.
SABIO-RKQ8TCT0.

Miscellaneous databases

ChiTaRSiCERK. human.
GeneWikiiCERK.
GenomeRNAii64781.
PROiQ8TCT0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100422.
CleanExiHS_CERK.
ExpressionAtlasiQ8TCT0. baseline and differential.
GenevisibleiQ8TCT0. HS.

Family and domain databases

InterProiIPR001206. Diacylglycerol_kinase_cat_dom.
IPR016064. NAD/diacylglycerol_kinase.
[Graphical view]
PfamiPF00781. DAGK_cat. 1 hit.
[Graphical view]
SMARTiSM00046. DAGKc. 1 hit.
[Graphical view]
SUPFAMiSSF111331. SSF111331. 3 hits.
PROSITEiPS50146. DAGK. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCERK1_HUMAN
AccessioniPrimary (citable) accession number: Q8TCT0
Secondary accession number(s): A0JNT4
, A8K611, Q6NX59, Q9BYB3, Q9UGE5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: June 1, 2002
Last modified: November 30, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.