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Protein

Ceramide kinase

Gene

CERK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • dihydroceramide kinase activity Source: UniProtKB-EC
  • magnesium ion binding Source: UniProtKB
  • NAD+ kinase activity Source: InterPro

GO - Biological processi

  • ceramide metabolic process Source: UniProtKB
  • glycosphingolipid metabolic process Source: Reactome

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Calcium, Magnesium, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.138 2681
ReactomeiR-HSA-1660662 Glycosphingolipid metabolism
SABIO-RKiQ8TCT0

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

EuPathDBiHostDB:ENSG00000100422.13
HGNCiHGNC:19256 CERK
MIMi610307 gene
neXtProtiNX_Q8TCT0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi74154

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

HPAiHPA064699

Interactioni

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi122291, 48 interactors
IntActiQ8TCT0, 47 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

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.50.10330, 1 hit
InterProiView protein in InterPro
IPR017438 ATP-NAD_kinase_N
IPR001206 Diacylglycerol_kinase_cat_dom
IPR016064 NAD/diacylglycerol_kinase_sf
PfamiView protein in Pfam
PF00781 DAGK_cat, 1 hit
SMARTiView protein in SMART
SM00046 DAGKc, 1 hit
SUPFAMiSSF111331 SSF111331, 3 hits
PROSITEiView protein in PROSITE
PS50146 DAGK, 1 hit

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 dbSNP:rs16995615Ensembl.1
Natural variantiVAR_053686211T → M. Corresponds to variant dbSNP:rs9306515Ensembl.1
Natural variantiVAR_053687306L → F. Corresponds to variant dbSNP:rs13057352Ensembl.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 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
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

Similar proteinsi

Entry informationi

Entry nameiCERK1_HUMAN
AccessioniPrimary (citable) accession number: Q8TCT0
Secondary accession number(s): A0JNT4
, A8K611, Q6NX59, Q9BYB3, Q9UGE5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: June 1, 2002
Last modified: July 18, 2018
This is version 143 of the entry and version 1 of the sequence. See 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

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