P02655 (APOC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apolipoprotein C-II
Short name=Apo-CII
Short name=ApoC-II

Alternative name(s):
Apolipoprotein C2

Gene names

Name:	APOC2
Synonyms:	APC2

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	101 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	Component of the very low density lipoprotein (VLDL) fraction in plasma, and is an activator of several triacylglycerol lipases. The association of APOC2 with plasma chylomicrons, VLDL, and HDL is reversible, a function of the secretion and catabolism of triglyceride-rich lipoproteins, and changes rapidly.
Subcellular location	Secreted.
Tissue specificity	Secreted in plasma.
Involvement in disease	Hyperlipoproteinemia 1B (HLPP1B) [MIM:207750]: Autosomal recessive trait characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23
Sequence similarities	Belongs to the apolipoprotein C2 family.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism Lipid transport Transport
Cellular component	Chylomicron Secreted VLDL
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hyperlipidemia
Domain	Signal
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol efflux Inferred from direct assay PubMed 11162594. Source: BHF-UCL cholesterol homeostasis Inferred by curator PubMed 15778093. Source: BHF-UCL chylomicron remnant clearance Inferred from direct assay PubMed 4020294. Source: BHF-UCL chylomicron remodeling Inferred by curator PubMed 10727238. Source: BHF-UCL high-density lipoprotein particle clearance Inferred from mutant phenotype PubMed 15778093. Source: BHF-UCL lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW lipoprotein metabolic process Traceable author statement. Source: Reactome negative regulation of cholesterol transport Inferred from mutant phenotype PubMed 15778093. Source: BHF-UCL negative regulation of lipid metabolic process Inferred from direct assay PubMed 182536. Source: BHF-UCL negative regulation of receptor-mediated endocytosis Inferred from direct assay PubMed 1917954. Source: BHF-UCL negative regulation of very-low-density lipoprotein particle clearance Inferred from direct assay PubMed 1917954. Source: BHF-UCL phospholipid efflux Inferred from direct assay PubMed 11162594. Source: BHF-UCL phototransduction, visible light Traceable author statement. Source: Reactome positive regulation of fatty acid biosynthetic process Inferred from direct assay PubMed 10727238. Source: BHF-UCL positive regulation of lipoprotein lipase activity Inferred from direct assay PubMed 10727238PubMed 15878877. Source: BHF-UCL positive regulation of phospholipase activity Inferred from direct assay PubMed 10727238. Source: BHF-UCL positive regulation of phospholipid catabolic process Inferred from direct assay PubMed 10727238. Source: BHF-UCL positive regulation of triglyceride catabolic process Inferred from direct assay PubMed 10727238. Source: BHF-UCL positive regulation of very-low-density lipoprotein particle remodeling Inferred by curator PubMed 10727238. Source: BHF-UCL retinoid metabolic process Traceable author statement. Source: Reactome reverse cholesterol transport Inferred by curator PubMed 15778093. Source: BHF-UCL small molecule metabolic process Traceable author statement. Source: Reactome triglyceride homeostasis Inferred from mutant phenotype PubMed 17018885. Source: BHF-UCL very-low-density lipoprotein particle remodeling Traceable author statement PubMed 15778093. Source: BHF-UCL
Cellular_component	chylomicron Inferred from direct assay PubMed 8245722. Source: BHF-UCL early endosome Traceable author statement. Source: Reactome intermediate-density lipoprotein particle Inferred from direct assay PubMed 17336988. Source: BHF-UCL low-density lipoprotein particle Inferred from direct assay PubMed 8245722. Source: BHF-UCL spherical high-density lipoprotein particle Inferred from direct assay PubMed 16682745. Source: BHF-UCL very-low-density lipoprotein particle Inferred from direct assay PubMed 8245722. Source: BHF-UCL
Molecular_function	lipase inhibitor activity Inferred from direct assay PubMed 182536. Source: BHF-UCL lipid binding Inferred from direct assay PubMed 10727238. Source: BHF-UCL lipoprotein lipase activator activity Inferred from direct assay PubMed 10727238. Source: BHF-UCL phospholipase activator activity Inferred from direct assay PubMed 10727238. Source: BHF-UCL protein homodimerization activity Inferred from mutant phenotype PubMed 8245722. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.13 Ref.14

Chain

23 – 101

79

Apolipoprotein C-II

PRO_0000002024

Regions

Region

23 – 38

16

O-glycosylated at one site

Region

43 – 51

9

Lipid binding

Region

55 – 78

24

Lipoprotein lipase cofactor

Natural variations

Natural variant

41

1

K → T. Ref.21 Ref.22

VAR_000639

Natural variant

48

1

W → R in HLPP1B; variant Wakayama. Ref.23

VAR_000640

Natural variant

60

1

E → K in San Francisco; found in hyperlipidemic patients. Ref.20
Corresponds to variant rs5122 [ dbSNP | Ensembl ].

VAR_000641

Natural variant

77

1

K → Q in Africa. Ref.19 Ref.24
Corresponds to variant rs5126 [ dbSNP | Ensembl ].

VAR_000642

Experimental info

Sequence conflict

36

1

F → L Ref.7

Sequence conflict

36

1

F → L Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

101

Helix Strand Turn

Details...

Beta strand

28 – 31

4

Helix

37 – 57

21

Turn

58 – 61

4

Beta strand

62 – 64

3

Turn

68 – 70

3

Beta strand

71 – 74

4

Turn

75 – 77

3

Turn

79 – 81

3

Beta strand

86 – 88

3

Helix

92 – 94

3

Helix

97 – 99

3

Sequences

	Sequence		Length	Mass (Da)
	P02655 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 51CB86FEDB174D84	FASTA	101	11,284
	10 20 30 40 50 60 MGTRLLPALF LVLLVLGFEV QGTQQPQQDE MPSPTFLTQV KESLSSYWES AKTAAQNLYE 70 80 90 100 KTYLPAVDEK LRDLYSKSTA AMSTYTGIFT DQVLSVLKGE E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human preproapolipoprotein C-II gene. Complete nucleic acid sequence and genomic organization." Fojo S.S., Law S.W., Brewer H.B. Jr. FEBS Lett. 213:221-226(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Human apolipoprotein C-II: complete nucleic acid sequence of preapolipoprotein C-II." Fojo S.S., Law S.W., Brewer H.B. Jr. Proc. Natl. Acad. Sci. U.S.A. 81:6354-6357(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA abundance." Sharpe C.R., Sidoli A., Shelley C.S., Lucero M.A., Shoulders C.C., Baralle F.E. Nucleic Acids Res. 12:3917-3932(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"The human apolipoprotein C-II gene sequence contains a novel chromosome 19-specific minisatellite in its third intron." Das H.K., Jackson C.L., Miller D.A., Leff T., Breslow J.L. J. Biol. Chem. 262:4787-4793(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"The structure of the human apolipoprotein C-II gene. Electron microscopic analysis of RNA:DNA hybrids, complete nucleotide sequence, and identification of 5' homologous sequences among apolipoprotein genes." Wei C.F., Tsao Y.K., Robberson D.L., Gotto A.M. Jr., Brown K., Chan L. J. Biol. Chem. 260:15211-15221(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[6]	Nickerson D.A., Smith J.D., Fullerton S.M., Clark A.G., Stengard J.H., Salomaa V., Boerwinkle E., Sing C.F., Weiss K.M. Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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]. Tissue: Skeletal muscle.
[11]	"The isolation and characterization of cDNA clones for human apolipoprotein CII." Myklebost O., Williamson B., Markham A.F., Myklebost S.R., Rogers J., Woods D.E., Humphries S.E. J. Biol. Chem. 259:4401-4404(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-101.
[12]	"Isolation of cDNA and genomic clones for apolipoprotein C-II." Jackson C.L., Bruns G.A.P., Breslow J.L. Methods Enzymol. 128:788-800(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 11-101.
[13]	"Amino acid sequence of human plasma apolipoprotein C-II from normal and hyperlipoproteinemic subjects." Hospattankar A.V., Fairwell T., Ronan R., Brewer H.B. Jr. J. Biol. Chem. 259:318-322(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-101.
[14]	"Primary structure of very low density apolipoprotein C-II of human plasma." Jackson R.L., Baker H.N., Gilliam E.B., Gotto A.M. Jr. Proc. Natl. Acad. Sci. U.S.A. 74:1942-1945(1977) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 23-101.
[15]	"Expression of the apolipoprotein C-II gene during myelomonocytic differentiation of human leukemic cells." Chun E.M., Park Y.J., Kang H.S., Cho H.M., Jun D.Y., Kim Y.H. J. Leukoc. Biol. 69:645-650(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 77-101.
[16]	"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins." Halim A., Ruetschi U., Larson G., Nilsson J. J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, MASS SPECTROMETRY.
[17]	"Sequence specific 1H-NMR assignments and secondary structure of a carboxy-terminal functional fragment of apolipoprotein CII." Lycksell P.-O., Oehman A., Bengtsson-Olivecrona G., Johansson L.B.-A., Wijmenga S.S., Wernic D., Graeslund A. Eur. J. Biochem. 205:223-231(1992) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 72-101.
[18]	"A refined three-dimensional solution structure of a carboxy terminal fragment of apolipoprotein CII." Oehman A., Lycksell P.-O., Graeslund A. Eur. Biophys. J. 22:351-357(1993) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 72-101.
[19]	"A variant primary structure of apolipoprotein C-II in individuals of African descent." Menzel H.-J., Kane J.P., Malloy M.J., Havel R.J. J. Clin. Invest. 77:595-601(1986) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AFRICA GLN-77.
[20]	"Molecular cloning and characteristics of a new apolipoprotein C-II mutant identified in three unrelated individuals with hypercholesterolemia and hypertriglyceridemia." Pullinger C.R., Zysow B.R., Hennessy L.K., Frost P.H., Malloy M.J., Kanr J.P. Hum. Mol. Genet. 2:69-74(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SAN FRANCISCO LYS-60.
[21]	"An apolipoprotein CII mutation, CII Lys-19-->Thr identified in patients with hyperlipidemia." Hegele R.A., Connelly P.W., Maguire G.F., Huff M.W., Leiter L., Wolfe B.M., Evans A.J., Little J.A. Dis. Markers 9:73-80(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THR-41.
[22]	"The apolipoprotein C-II variant apoC-II Lys-19-->Thr is not associated with dyslipidemia in an affected kindred." Zysow B.R., Pullinger C.R., Hennessy L.K., Farese R.V. Jr., Ghassemzadeh M., Kane J.P. Clin. Genet. 45:292-297(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT THR-41.
[23]	"A missense mutation (Trp 26-->Arg) in exon 3 of the apolipoprotein CII gene in a patient with apolipoprotein CII deficiency (apo CII-Wakayama)." Inadera H., Hibino A., Kobayashi J., Kanzaki T., Shirai K., Yukawa S., Saito Y., Yoshida S. Biochem. Biophys. Res. Commun. 193:1174-1183(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HLPP1B WAKAYAMA ARG-48.
[24]	"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLN-77.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X05151 Genomic DNA. Translation: CAA28798.1.
X00568 mRNA. Translation: CAA25234.1.
J02698 Genomic DNA. Translation: AAA98743.1.
AY422955 Genomic DNA. Translation: AAQ91814.1.
BT006708 mRNA. Translation: AAP35354.1.
FJ525875 Genomic DNA. Translation: ACN81313.1.
CH471126 Genomic DNA. Translation: EAW57311.1.
BC005348 mRNA. Translation: AAH05348.3.
M29844 mRNA. Translation: AAA51743.1.
M10612 Genomic DNA. Translation: AAB59380.1.
AF113884 mRNA. Translation: AAD28193.1.

IPI

IPI00021856.

PIR

LPHUC2. A24238.

RefSeq

NP_000474.2. NM_000483.4.

UniGene

Hs.75615.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BY6	NMR	-	A	66-101	[»]
1I5J	NMR	-	A	23-101	[»]
1O8T	NMR	-	A	23-101	[»]
1SOH	NMR	-	A	23-101	[»]

ProteinModelPortal

P02655.

ModBase

Search...

Protein-protein interaction databases

IntAct

P02655. 1 interaction.

STRING

9606.ENSP00000252490.

PTM databases

PhosphoSite

P02655.

Polymorphism databases

DMDM

114022.

2D gel databases

DOSAC-COBS-2DPAGE

P02655.

SWISS-2DPAGE

P02655.

Proteomic databases

PaxDb

P02655.

PeptideAtlas

P02655.

PRIDE

P02655.

Protocols and materials databases

DNASU

344.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000590360; ENSP00000466775; ENSG00000234906.

GeneID

344.

KEGG

hsa:344.

Organism-specific databases

CTD

344.

GeneCards

GC19P045449.

HGNC

HGNC:609. APOC2.

HPA

HPA055877.

MIM

207750. phenotype.
608083. gene.

neXtProt

NX_P02655.

Orphanet

309020. Familial apolipoprotein C-II deficiency.

PharmGKB

PA52.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG25045.

HOGENOM

HOG000034002.

HOVERGEN

HBG050548.

InParanoid

P02655.

OMA

GIFTDQV.

OrthoDB

EOG4SXNF3.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P02655.

Bgee

P02655.

CleanEx

HS_APC2.
HS_APOC2.

Genevestigator

P02655.

GermOnline

ENSG00000130207. Homo sapiens.

Family and domain databases

Gene3D

1.10.1440.10. 1 hit.

InterPro

IPR008019. Apo-CII.
IPR023121. ApoC-II_domain.
[Graphical view]

PANTHER

PTHR16566. PTHR16566. 1 hit.

Pfam

PF05355. Apo-CII. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P02655.

GenomeRNAi

344.

NextBio

1419.

PMAP-CutDB

P02655.

SOURCE

Search...

Entry information

Entry name

APOC2_HUMAN

Accession

Primary (citable) accession number: P02655
Secondary accession number(s): C0JYY4 , Q9BS39, Q9UDE3, Q9UNK3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	May 29, 2013
This is version 161 of the entry and version 1 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.