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P11597 (CETP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cholesteryl ester transfer protein
Alternative name(s):
Lipid transfer protein I
Gene names
Name:CETP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length493 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the transfer of insoluble cholesteryl esters in the reverse transport of cholesterol.

Subcellular location

Secretedextracellular space.

Tissue specificity

Expressed by the liver and secreted in plasma.

Polymorphism

Genetic variations in CETP define the high density lipoprotein cholesterol level quantitative trait locus 10 (HDLCQ10) [MIM:143470].

Involvement in disease

Hyperalphalipoproteinemia 1 (HALP1) [MIM:143470]: A condition characterized by high levels of high density lipoprotein (HDL) and increased HDL cholesterol levels.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.15

Sequence similarities

Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.

Ontologies

Keywords
   Biological processCholesterol metabolism
Lipid metabolism
Lipid transport
Steroid metabolism
Sterol metabolism
Transport
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAtherosclerosis
Disease mutation
   DomainSignal
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol homeostasis

Inferred from mutant phenotype PubMed 2586614. Source: BHF-UCL

cholesterol metabolic process

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

cholesterol transport

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

high-density lipoprotein particle remodeling

Inferred from mutant phenotype PubMed 2586614. Source: BHF-UCL

lipid homeostasis

Inferred from direct assay PubMed 3818596. Source: BHF-UCL

lipid transport

Inferred from direct assay PubMed 3818596. Source: BHF-UCL

lipoprotein metabolic process

Traceable author statement. Source: Reactome

low-density lipoprotein particle remodeling

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

negative regulation of macrophage derived foam cell differentiation

Inferred by curator PubMed 16670775. Source: BHF-UCL

phosphatidylcholine metabolic process

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

phospholipid homeostasis

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

phospholipid transport

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

receptor-mediated endocytosis

Traceable author statement. Source: Reactome

regulation of cholesterol efflux

Inferred from mutant phenotype PubMed 16670775. Source: BHF-UCL

reverse cholesterol transport

Inferred by curator PubMed 7583561. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride homeostasis

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

triglyceride metabolic process

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

very-low-density lipoprotein particle remodeling

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 3104518. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

high-density lipoprotein particle

Inferred from direct assay PubMed 3104518. Source: BHF-UCL

vesicle

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

   Molecular_functioncholesterol binding

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

cholesterol transporter activity

Inferred from direct assay PubMed 2833496Ref.1. Source: BHF-UCL

lipid binding

Inferred from direct assay PubMed 3818596. Source: BHF-UCL

lipid transporter activity

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

phosphatidylcholine binding

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

phospholipid transporter activity

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

triglyceride binding

Inferred from direct assay PubMed 2833496. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P11597-1)

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.
Isoform 2 (identifier: P11597-2)

The sequence of this isoform differs from the canonical sequence as follows:
     251-310: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717
Chain18 – 493476Cholesteryl ester transfer protein
PRO_0000017155

Amino acid modifications

Glycosylation1051N-linked (GlcNAc...) (complex) Ref.9
Glycosylation2571N-linked (GlcNAc...) Ref.8
Glycosylation3581N-linked (GlcNAc...) Ref.8
Glycosylation4131N-linked (GlcNAc...) Potential
Disulfide bond160 ↔ 201 Ref.10

Natural variations

Alternative sequence251 – 31060Missing in isoform 2.
VSP_023645
Natural variant151A → G. Ref.16
Corresponds to variant rs34065661 [ dbSNP | Ensembl ].
VAR_017018
Natural variant1541R → W.
Corresponds to variant rs34716057 [ dbSNP | Ensembl ].
VAR_033098
Natural variant1681L → P in HALP1; reduced secretion into plasma. Ref.15
VAR_033099
Natural variant2991R → C in HALP1; reduced secretion into plasma. Ref.15
VAR_033100
Natural variant3311G → S. Ref.13
Corresponds to variant rs5881 [ dbSNP | Ensembl ].
VAR_013919
Natural variant3851V → M. Ref.16
Corresponds to variant rs34855278 [ dbSNP | Ensembl ].
VAR_017019
Natural variant3901A → P. Ref.13 Ref.16
Corresponds to variant rs5880 [ dbSNP | Ensembl ].
VAR_013920
Natural variant4221V → I. Ref.1 Ref.3 Ref.4 Ref.7 Ref.13 Ref.16
Corresponds to variant rs5882 [ dbSNP | Ensembl ].
VAR_013921
Natural variant4551V → M.
Corresponds to variant rs2228667 [ dbSNP | Ensembl ].
VAR_031127
Natural variant4591D → G in HALP1. Ref.12
Corresponds to variant rs2303790 [ dbSNP | Ensembl ].
VAR_004172
Natural variant4681R → Q. Ref.16
Corresponds to variant rs1800777 [ dbSNP | Ensembl ].
VAR_013922
Natural variant4861V → M. Ref.13
Corresponds to variant rs5887 [ dbSNP | Ensembl ].
VAR_013923

Experimental info

Mutagenesis1551T → Y: Reduces triglyceride transfer and cholesteryl ester transfer 5-fold. Ref.10
Mutagenesis2151V → W: Reduces triglyceride transfer 10-fold. No effect on cholesteryl ester transfer. Ref.10
Mutagenesis2181R → S: Reduces triglyceride transfer 10-fold. Slight reduction of cholesteryl ester transfer. Ref.10
Mutagenesis2471S → A: Reduces triglyceride transfer 5-fold. Slight reduction of cholesteryl ester transfer. Ref.10
Mutagenesis2821F → R: Not secreted. Ref.10
Mutagenesis2871F → R: Not secreted. Ref.10
Mutagenesis3091F → D: Not secreted. Ref.10
Mutagenesis3131L → Q: Reduces cholesteryl ester transfer by 60%. Ref.10
Mutagenesis3921Y → S: Not secreted. Ref.10
Mutagenesis3991L → W: Not secreted. Ref.10
Mutagenesis4331V → R: Reduces activity by 60%. Ref.10

Secondary structure

.................................................................... 493
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 19, 2005. Version 2.
Checksum: CD7762766A9B062E

FASTA49354,756
        10         20         30         40         50         60 
MLAATVLTLA LLGNAHACSK GTSHEAGIVC RITKPALLVL NHETAKVIQT AFQRASYPDI 

        70         80         90        100        110        120 
TGEKAMMLLG QVKYGLHNIQ ISHLSIASSQ VELVEAKSID VSIQNVSVVF KGTLKYGYTT 

       130        140        150        160        170        180 
AWWLGIDQSI DFEIDSAIDL QINTQLTCDS GRVRTDAPDC YLSFHKLLLH LQGEREPGWI 

       190        200        210        220        230        240 
KQLFTNFISF TLKLVLKGQI CKEINVISNI MADFVQTRAA SILSDGDIGV DISLTGDPVI 

       250        260        270        280        290        300 
TASYLESHHK GHFIYKNVSE DLPLPTFSPT LLGDSRMLYF WFSERVFHSL AKVAFQDGRL 

       310        320        330        340        350        360 
MLSLMGDEFK AVLETWGFNT NQEIFQEVVG GFPSQAQVTV HCLKMPKISC QNKGVVVNSS 

       370        380        390        400        410        420 
VMVKFLFPRP DQQHSVAYTF EEDIVTTVQA SYSKKKLFLS LLDFQITPKT VSNLTESSSE 

       430        440        450        460        470        480 
SVQSFLQSMI TAVGIPEVMS RLEVVFTALM NSKGVSLFDI INPEIITRDG FLLLQMDFGF 

       490 
PEHLLVDFLQ SLS 

« Hide

Isoform 2 [UniParc].

Checksum: ED675FD1456F78F7
Show »

FASTA43347,787

References

« Hide 'large scale' references
[1]"Cloning and sequencing of human cholesteryl ester transfer protein cDNA."
Drayna D., Jarnagin A.S., McLean J., Henzel W., Kohr W., Fielding C., Lawn R.
Nature 327:632-634(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, VARIANT ILE-422.
[2]"Organization of the human cholesteryl ester transfer protein gene."
Agellon L.B., Quinet E.M., Gillette T.G., Drayna D.T., Brown M.L., Tall A.R.
Biochemistry 29:1372-1376(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D., Toth E.J., Nickerson D.A.
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-422.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-422.
Tissue: Pancreas and Spleen.
[5]"Human cholesteryl ester transfer protein gene proximal promoter contains dietary cholesterol positive responsive elements and mediates expression in small intestine and periphery while predominant liver and spleen expression is controlled by 5'-distal sequences. Cis-acting sequences mapped in transgenic mice."
Oliveira C.F.O., Chouinard R.A., Agellon L.B., Bruce C., Ma L., Walsh A., Breslow J.L., Tall A.R.
J. Biol. Chem. 271:31831-31838(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
[6]"Sequencing of the cholesteryl ester transfer protein 5' regulatory region using artificial transposons."
Williams S., Hayes L., Elsenboss L., Williams A., Andre C., Abramson R., Thompson J.F., Milos P.M.
Gene 197:101-107(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
[7]Dinchuk J.E., Hart J.T., Wirak D.O.
Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 9-493 (ISOFORM 2), VARIANT ILE-422.
Tissue: Liver.
[8]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-257 AND ASN-358.
Tissue: Plasma.
[9]"A strategy for precise and large scale identification of core fucosylated glycoproteins."
Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.
Mol. Cell. Proteomics 8:913-923(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-105.
[10]"Crystal structure of cholesteryl ester transfer protein reveals a long tunnel and four bound lipid molecules."
Qiu X., Mistry A., Ammirati M.J., Chrunyk B.A., Clark R.W., Cong Y., Culp J.S., Danley D.E., Freeman T.B., Geoghegan K.F., Griffor M.C., Hawrylik S.J., Hayward C.M., Hensley P., Hoth L.R., Karam G.A., Lira M.E., Lloyd D.B. expand/collapse author list , McGrath K.M., Stutzman-Engwall K.J., Subashi A.K., Subashi T.A., Thompson J.F., Wang I.-K., Zhao H., Seddon A.P.
Nat. Struct. Mol. Biol. 14:106-113(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 19-493 IN COMPLEX WITH LIPID, DISULFIDE BOND, MUTAGENESIS OF THR-155; VAL-215; ARG-218; SER-247; PHE-282; PHE-287; PHE-309; LEU-313; TYR-392; LEU-399 AND VAL-433.
[11]"Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation."
Inazu A., Brown M.L., Hesler C.B., Agellon L.B., Koizumi J., Takata K., Maruhama Y., Mabuchi H., Tall A.R.
N. Engl. J. Med. 323:1234-1238(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HALP1.
[12]"A missense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins."
Takahashi K., Jiang X.-C., Sakai N., Yamashita S., Hirano K., Bujo H., Yamazaki H., Kusunoki J., Miura T., Kussie P., Matsuzawa Y., Saito Y., Tall A.
J. Clin. Invest. 92:2060-2064(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HALP1 GLY-459.
[13]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-331; PRO-390; ILE-422 AND MET-486.
[14]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
[15]"Two novel missense mutations in the CETP gene in Japanese hyperalphalipoproteinemic subjects: high-throughput assay by Invader assay."
Nagano M., Yamashita S., Hirano K., Ito M., Maruyama T., Ishihara M., Sagehashi Y., Oka T., Kujiraoka T., Hattori H., Nakajima N., Egashira T., Kondo M., Sakai N., Matsuzawa Y.
J. Lipid Res. 43:1011-1018(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HALP1 PRO-168 AND CYS-299, CHARACTERIZATION OF VARIANTS HALP1 PRO-168 AND CYS-299.
[16]"Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors."
Morabia A., Cayanis E., Costanza M.C., Ross B.M., Flaherty M.S., Alvin G.B., Das K., Gilliam T.C.
Hum. Mol. Genet. 12:2733-2743(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLY-15; MET-385; PRO-390; ILE-422 AND GLN-468.
+Additional computationally mapped references.

Web resources

SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

Cholesterylester transfer protein entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M30185 mRNA. Translation: AAA51977.1.
M32998 expand/collapse EMBL AC list , M32992, M32993, M32994, M32995, M32996, M32997 Genomic DNA. Translation: AAA51978.1.
AY422211 Genomic DNA. Translation: AAR03500.1.
BC025739 mRNA. Translation: AAH25739.1.
U71187 Genomic DNA. Translation: AAD14876.1.
AF027656 Genomic DNA. Translation: AAB86604.1.
M83573 mRNA. Translation: AAB59388.1.
CCDSCCDS10772.1. [P11597-1]
CCDS67032.1. [P11597-2]
PIRA26941.
RefSeqNP_000069.2. NM_000078.2. [P11597-1]
UniGeneHs.89538.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2OBDX-ray2.10A18-493[»]
4EWSX-ray2.59A18-493[»]
4F2AX-ray3.11A18-493[»]
ProteinModelPortalP11597.
SMRP11597. Positions 22-493.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107498. 2 interactions.
IntActP11597. 3 interactions.
STRING9606.ENSP00000200676.

Chemistry

BindingDBP11597.
ChEMBLCHEMBL3572.

PTM databases

PhosphoSiteP11597.

Polymorphism databases

DMDM71153497.

Proteomic databases

PaxDbP11597.
PeptideAtlasP11597.
PRIDEP11597.

Protocols and materials databases

DNASU1071.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000200676; ENSP00000200676; ENSG00000087237. [P11597-1]
ENST00000379780; ENSP00000369106; ENSG00000087237. [P11597-2]
GeneID1071.
KEGGhsa:1071.
UCSCuc002eki.2. human. [P11597-1]
uc002ekj.2. human. [P11597-2]

Organism-specific databases

CTD1071.
GeneCardsGC16P056996.
HGNCHGNC:1869. CETP.
MIM118470. gene.
143470. phenotype.
neXtProtNX_P11597.
Orphanet79506. Cholesterol-ester transfer protein deficiency.
PharmGKBPA108.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG252260.
HOGENOMHOG000111553.
HOVERGENHBG005310.
InParanoidP11597.
KOK16835.
OMAPGWLKQL.
OrthoDBEOG783MV4.
PhylomeDBP11597.
TreeFamTF333484.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressP11597.
BgeeP11597.
CleanExHS_CETP.
GenevestigatorP11597.

Family and domain databases

InterProIPR017943. Bactericidal_perm-incr_a/b_dom.
IPR017130. Cholesteryl_ester_transfer.
IPR001124. Lipid-bd_serum_glycop_C.
IPR017954. Lipid-bd_serum_glycop_CS.
IPR017942. Lipid-bd_serum_glycop_N.
[Graphical view]
PANTHERPTHR10504:SF12. PTHR10504:SF12. 1 hit.
PfamPF01273. LBP_BPI_CETP. 1 hit.
PF02886. LBP_BPI_CETP_C. 1 hit.
[Graphical view]
PIRSFPIRSF037185. Cholesteryl_ester_transf. 1 hit.
SMARTSM00328. BPI1. 1 hit.
SM00329. BPI2. 1 hit.
[Graphical view]
SUPFAMSSF55394. SSF55394. 2 hits.
PROSITEPS00400. LBP_BPI_CETP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP11597.
GeneWikiCholesterylester_transfer_protein.
GenomeRNAi1071.
NextBio4472.
PROP11597.
SOURCESearch...

Entry information

Entry nameCETP_HUMAN
AccessionPrimary (citable) accession number: P11597
Secondary accession number(s): Q13987, Q13988, Q53YZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: July 19, 2005
Last modified: July 9, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM