P11597 (CETP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cholesteryl ester transfer protein

Alternative name(s):
Lipid transfer protein I

Gene names

Name:

CETP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	493 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the transfer of insoluble cholesteryl esters in the reverse transport of cholesterol.
Subcellular location	Secreted › extracellular 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.10 Ref.11 Ref.14
Sequence similarities	Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Lipid transport Steroid metabolism Sterol metabolism Transport
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Atherosclerosis Disease mutation
Domain	Signal
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol homeostasis Inferred from mutant phenotype PubMed 2586614. Source: BHF-UCL cholesterol metabolic process Inferred from direct assay PubMed 2833496. Source: BHF-UCL high-density lipoprotein particle remodeling Inferred from mutant phenotype PubMed 2586614. 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 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 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_component	high-density lipoprotein particle Inferred from direct assay PubMed 3104518. Source: BHF-UCL vesicle Inferred from direct assay PubMed 2833496. Source: BHF-UCL
Molecular_function	cholesterol binding Inferred from direct assay PubMed 2833496. Source: BHF-UCL cholesterol transporter activity Inferred from direct assay PubMed 2833496Ref.1. 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Chain

18 – 493

476

Cholesteryl ester transfer protein

PRO_0000017155

Amino acid modifications

Glycosylation

105

1

N-linked (GlcNAc...) Potential

Glycosylation

257

1

N-linked (GlcNAc...) Ref.8

Glycosylation

358

1

N-linked (GlcNAc...) Ref.8

Glycosylation

413

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

251 – 310

60

Missing in isoform 2.

VSP_023645

Natural variant

15

1

A → G. Ref.15
Corresponds to variant rs34065661 [ dbSNP | Ensembl ].

VAR_017018

Natural variant

154

1

R → W.
Corresponds to variant rs34716057 [ dbSNP | Ensembl ].

VAR_033098

Natural variant

168

1

L → P in HALP1; reduced secretion into plasma. Ref.14

VAR_033099

Natural variant

299

1

R → C in HALP1; reduced secretion into plasma. Ref.14

VAR_033100

Natural variant

331

1

G → S. Ref.12
Corresponds to variant rs5881 [ dbSNP | Ensembl ].

VAR_013919

Natural variant

385

1

V → M. Ref.15
Corresponds to variant rs34855278 [ dbSNP | Ensembl ].

VAR_017019

Natural variant

390

1

A → P. Ref.12 Ref.15
Corresponds to variant rs5880 [ dbSNP | Ensembl ].

VAR_013920

Natural variant

422

1

V → I. Ref.1 Ref.3 Ref.4 Ref.7 Ref.12 Ref.15
Corresponds to variant rs5882 [ dbSNP | Ensembl ].

VAR_013921

Natural variant

455

1

V → M.
Corresponds to variant rs2228667 [ dbSNP | Ensembl ].

VAR_031127

Natural variant

459

1

D → G in HALP1. Ref.11
Corresponds to variant rs2303790 [ dbSNP | Ensembl ].

VAR_004172

Natural variant

468

1

R → Q. Ref.15
Corresponds to variant rs1800777 [ dbSNP | Ensembl ].

VAR_013922

Natural variant

486

1

V → M. Ref.12
Corresponds to variant rs5887 [ dbSNP | Ensembl ].

VAR_013923

Experimental info

Mutagenesis

155

1

T → Y: Reduces triglyceride transfer and cholesteryl ester transfer 5-fold. Ref.9

Mutagenesis

215

1

V → W: Reduces triglyceride transfer 10-fold. No effect on cholesteryl ester transfer. Ref.9

Mutagenesis

218

1

R → S: Reduces triglyceride transfer 10-fold. Slight reduction of cholesteryl ester transfer. Ref.9

Mutagenesis

247

1

S → A: Reduces triglyceride transfer 5-fold. Slight reduction of cholesteryl ester transfer. Ref.9

Mutagenesis

282

1

F → R: Not secreted. Ref.9

Mutagenesis

287

1

F → R: Not secreted. Ref.9

Mutagenesis

309

1

F → D: Not secreted. Ref.9

Mutagenesis

313

1

L → Q: Reduces cholesteryl ester transfer by 60%. Ref.9

Mutagenesis

392

1

Y → S: Not secreted. Ref.9

Mutagenesis

399

1

L → W: Not secreted. Ref.9

Mutagenesis

433

1

V → R: Reduces activity by 60%. Ref.9

Secondary structure

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493

Helix Strand Turn

Details...

Beta strand

27 – 33

7

Helix

34 – 40

7

Helix

41 – 43

3

Helix

44 – 54

11

Beta strand

60 – 66

7

Turn

67 – 69

3

Beta strand

70 – 94

25

Turn

95 – 97

3

Beta strand

98 – 120

23

Helix

122 – 124

3

Beta strand

128 – 149

22

Beta strand

152 – 171

20

Helix

172 – 174

3

Helix

180 – 187

8

Helix

189 – 222

34

Beta strand

228 – 231

4

Beta strand

234 – 236

3

Beta strand

242 – 249

8

Beta strand

252 – 255

4

Helix

269 – 271

3

Beta strand

274 – 283

10

Helix

284 – 296

13

Beta strand

300 – 304

5

Helix

306 – 315

10

Helix

323 – 325

3

Helix

326 – 329

4

Helix

333 – 335

3

Beta strand

337 – 344

8

Beta strand

347 – 351

5

Beta strand

354 – 367

14

Helix

372 – 374

3

Beta strand

378 – 393

16

Beta strand

396 – 416

21

Helix

420 – 432

13

Helix

434 – 451

18

Turn

452 – 454

3

Helix

455 – 457

3

Beta strand

458 – 468

11

Beta strand

471 – 479

9

Helix

482 – 490

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 19, 2005. Version 2. Checksum: CD7762766A9B062E	FASTA	493	54,756
	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
	Isoform 2 [UniParc]. Checksum: ED675FD1456F78F7	FASTA	433	47,787
	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 AVLETWGFNT NQEIFQEVVG GFPSQAQVTV HCLKMPKISC QNKGVVVNSS 310 320 330 340 350 360 VMVKFLFPRP DQQHSVAYTF EEDIVTTVQA SYSKKKLFLS LLDFQITPKT VSNLTESSSE 370 380 390 400 410 420 SVQSFLQSMI TAVGIPEVMS RLEVVFTALM NSKGVSLFDI INPEIITRDG FLLLQMDFGF 430 PEHLLVDFLQ SLS

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. Tissue: Plasma.
[9]	"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. , 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, 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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	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)
[14]	"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.
[15]	"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 , 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.

IPI

IPI00006173.
IPI00641481.

PIR

A26941.

RefSeq

NP_000069.2. NM_000078.2.

UniGene

Hs.89538.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2OBD	X-ray	2.10	A	19-493	[»]
4EWS	X-ray	2.59	A	19-493	[»]
4F2A	X-ray	3.11	A	19-493	[»]

ProteinModelPortal

P11597.

ModBase

Search...

Protein-protein interaction databases

IntAct

P11597. 3 interactions.

STRING

9606.ENSP00000200676.

PTM databases

PhosphoSite

P11597.

Polymorphism databases

DMDM

71153497.

Proteomic databases

PaxDb

P11597.

PeptideAtlas

P11597.

PRIDE

P11597.

Protocols and materials databases

DNASU

1071.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000200676; ENSP00000200676; ENSG00000087237.
ENST00000379780; ENSP00000369106; ENSG00000087237.

GeneID

1071.

KEGG

hsa:1071.

UCSC

uc002eki.2. human.
uc002ekj.2. human.

Organism-specific databases

CTD

1071.

GeneCards

GC16P056996.

HGNC

HGNC:1869. CETP.

MIM

118470. gene.
143470. phenotype.

neXtProt

NX_P11597.

Orphanet

79506. Cholesterol-ester transfer protein deficiency.

PharmGKB

PA108.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG252260.

HOGENOM

HOG000111553.

HOVERGEN

HBG005310.

InParanoid

P11597.

KO

K16835.

OMA

PKISCQN.

OrthoDB

EOG4GMTX5.

PhylomeDB

P11597.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P11597.

Bgee

P11597.

CleanEx

HS_CETP.

Genevestigator

P11597.

GermOnline

ENSG00000087237. Homo sapiens.

Family and domain databases

InterPro

IPR017943. 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]

PANTHER

PTHR10504:SF12. PTHR10504:SF12. 1 hit.

Pfam

PF01273. LBP_BPI_CETP. 1 hit.
PF02886. LBP_BPI_CETP_C. 1 hit.
[Graphical view]

PIRSF

PIRSF037185. Cholesteryl_ester_transf. 1 hit.

SMART

SM00328. BPI1. 1 hit.
SM00329. BPI2. 1 hit.
[Graphical view]

SUPFAM

SSF55394. Bactericidal_perm-incr_a/b_dom. 2 hits.

PROSITE

PS00400. LBP_BPI_CETP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P11597.

ChEMBL

CHEMBL3572.

EvolutionaryTrace

P11597.

GenomeRNAi

1071.

NextBio

4472.

SOURCE

Search...

Entry information

Entry name

CETP_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 142 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.