P02647 (APOA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Apolipoprotein A-I
Short name=Apo-AI
Short name=ApoA-I

Alternative name(s):
Apolipoprotein A1

Cleaved into the following chain:

1. Apolipoprotein A-I(1-242)

Gene names

Name:

APOA1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	267 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	Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT). As part of the SPAP complex, activates spermatozoa motility. Ref.20
Subunit structure	Interacts with APOA1BP and CLU. Component of a sperm activating protein complex (SPAP), consisting of APOA1, an immunoglobulin heavy chain, an immunoglobulin light chain and albumin. Interacts with NDRG1. Ref.25 Ref.31 Ref.33
Subcellular location	Secreted.
Tissue specificity	Major protein of plasma HDL, also found in chylomicrons. Synthesized in the liver and small intestine. Ref.34
Post-translational modification	Palmitoylated. Ref.28 Phosphorylation sites are present in the extracelllular medium.
Involvement in disease	Defects in APOA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:604091]; also known as familial hypoalphalipoproteinemia (FHA). Inheritance is autosomal dominant. Ref.38 Ref.39 Defects in APOA1 are a cause of the low HDL levels observed in high density lipoprotein deficiency type 1 (HDLD1) [MIM:205400]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by the absence of plasma HDL, accumulation of cholesteryl esters, premature coronary artery disease, hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness. In HDLD1 patients, ApoA-I fails to associate with HDL probably because of the faulty conversion of pro-ApoA-I molecules into mature chains, either due to a defect in the converting enzyme activity or a specific structural defect in Tangier ApoA-I. Ref.38 Ref.39 Note=A mutation in APOA1 is the cause of amyloid polyneuropathy-nephropathy Iowa type (AMYLIOWA); also known as amyloidosis van Allen type or familial amyloid polyneuropathy type III. AMYLIOWA is a hereditary generalized amyloidosis due to deposition of amyloid mainly constituted by apolipoprotein A1. The clinical picture is dominated by neuropathy in the early stages of the disease and nephropathy late in the course. Death is due in most cases to renal amyloidosis. Severe peptic ulcer disease can occurr in some and hearing loss is frequent. Cataracts is present in several, but vitreous opacities are not observed. Ref.38 Ref.39 Ref.44 Ref.45 Defects in APOA1 are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. Ref.38 Ref.39 Ref.47
Sequence similarities	Belongs to the apolipoprotein A1/A4/E family.

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Lipid transport Steroid metabolism Transport
Cellular component	Amyloid HDL Secreted
Coding sequence diversity	Polymorphism
Disease	Amyloidosis Atherosclerosis Disease mutation Neuropathy
Domain	Repeat Signal
PTM	Glycation Glycoprotein Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	Cdc42 protein signal transduction Inferred from direct assay. Source: BHF-UCL G-protein coupled receptor signaling pathway Inferred from direct assay. Source: BHF-UCL cholesterol efflux Inferred from direct assay. Source: BHF-UCL cholesterol homeostasis Inferred from mutant phenotype. Source: BHF-UCL cholesterol import Inferred from mutant phenotype. Source: BHF-UCL high-density lipoprotein particle assembly Inferred from direct assay. Source: BHF-UCL high-density lipoprotein particle clearance Inferred by curator. Source: BHF-UCL high-density lipoprotein particle remodeling Inferred by curator. Source: BHF-UCL negative regulation of cytokine secretion involved in immune response Inferred from direct assay. Source: BHF-UCL negative regulation of interleukin-1 beta secretion Inferred from direct assay. Source: BHF-UCL negative regulation of very-low-density lipoprotein particle remodeling Inferred from direct assay. Source: BHF-UCL phosphatidylcholine biosynthetic process Inferred from direct assay. Source: BHF-UCL phospholipid efflux Inferred from direct assay. Source: BHF-UCL platelet activation Traceable author statement. Source: Reactome platelet degranulation Traceable author statement. Source: Reactome positive regulation of cholesterol esterification Inferred from direct assay. Source: BHF-UCL positive regulation of hydrolase activity Inferred from direct assay. Source: BHF-UCL protein stabilization Inferred from direct assay. Source: BHF-UCL reverse cholesterol transport Inferred from mutant phenotype. Source: BHF-UCL
Cellular component	endocytic vesicle Inferred from direct assay. Source: BHF-UCL endoplasmic reticulum lumen Traceable author statement. Source: Reactome plasma membrane Traceable author statement. Source: Reactome secretory granule Traceable author statement. Source: Reactome spherical high-density lipoprotein particle Inferred from direct assay. Source: BHF-UCL very-low-density lipoprotein particle Inferred from direct assay. Source: BHF-UCL
Molecular function	apolipoprotein A-I receptor binding Inferred from physical interaction. Source: BHF-UCL beta-amyloid binding Inferred from direct assay. Source: BHF-UCL cholesterol binding Inferred from direct assay. Source: BHF-UCL cholesterol transporter activity Inferred from mutant phenotype. Source: BHF-UCL enzyme binding Inferred from physical interaction. Source: BHF-UCL high-density lipoprotein particle receptor binding Inferred from physical interaction. Source: BHF-UCL identical protein binding Inferred from physical interaction. Source: BHF-UCL phosphatidylcholine-sterol O-acyltransferase activator activity Inferred from direct assay. Source: BHF-UCL phospholipid binding Inferred from direct assay. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	5	EBI-701692,EBI-77613

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Ref.5 Ref.16

Propeptide

19 – 24

6

PRO_0000001938

Chain

25 – 267

243

Apolipoprotein A-I

PRO_0000001939

Chain

25 – 266

242

Apolipoprotein A-I(1-242)

PRO_0000001940

Regions

Repeat

68 – 89

22

1

Repeat

90 – 111

22

2

Repeat

112 – 122

11

3; half-length

Repeat

123 – 144

22

4

Repeat

145 – 166

22

5

Repeat

167 – 188

22

6

Repeat

189 – 210

22

7

Repeat

211 – 232

22

8

Repeat

233 – 243

11

9; half-length

Repeat

244 – 267

24

10

Region

68 – 267

200

10 X approximate tandem repeats

Amino acid modifications

Modified residue

191

1

Phosphoserine Ref.34

Glycosylation

263

1

N-linked (Glc) (glycation) Ref.30

Natural variations

Natural variant

27

1

P → H in Munster-3C.

VAR_000605

Natural variant

27

1

P → R. Ref.49

VAR_000606

Natural variant

28

1

P → R in Munster-3B. Ref.49

VAR_000607

Natural variant

34

1

R → L in Baltimore. Ref.48
Corresponds to variant rs28929476 [ dbSNP | Ensembl ].

VAR_000608

Natural variant

50

1

G → R in AMYLIOWA. Ref.44 Ref.45
Corresponds to variant rs28931574 [ dbSNP | Ensembl ].

VAR_000609

Natural variant

61

1

A → T. Ref.10

VAR_025445

Natural variant

84

1

L → R in AMYL8. Ref.47

VAR_000610

Natural variant

92

1

T → I. Ref.54

VAR_017017

Natural variant

113

1

D → E. Ref.50

VAR_000611

Natural variant

119

1

A → D in Hita.

VAR_000612

Natural variant

126

1

D → H.
Corresponds to variant rs5077 [ dbSNP | Ensembl ].

VAR_016189

Natural variant

127

1

D → N in Munster-3A.

VAR_000613

Natural variant

131

1

K → M. Ref.50
Corresponds to variant rs4882 [ dbSNP | Ensembl ].

VAR_000615

Natural variant

131

1

Missing in Marburg/Munster-2.

VAR_000614

Natural variant

132

1

W → R in Tsushima.

VAR_000616

Natural variant

134

1

E → K in Fukuoka. Ref.46

VAR_000617

Natural variant

160

1

E → K in Norway. Ref.43

VAR_000618

Natural variant

163

1

E → G. Ref.50

VAR_000619

Natural variant

167

1

P → R in Giessen. Ref.42

VAR_000620

Natural variant

168

1

L → R in Zaragoza. Ref.53

VAR_000621

Natural variant

171

1

E → V. Ref.50

VAR_000622

Natural variant

180

1

V → E in Oita; 60% of normal apoA-I and normal HDL cholesterol levels. Rapidly cleared from plasma. Ref.52

VAR_021362

Natural variant

184

1

R → P.
Corresponds to variant rs5078 [ dbSNP | Ensembl ].

VAR_014609

Natural variant

189

1

P → R. Ref.49

VAR_000623

Natural variant

197

1

R → C in Milano; associated with decreased HDL levels and moderate increases in triglycerides; no evidence of association with premature vascular disease. Ref.40
Corresponds to variant rs28931573 [ dbSNP | Ensembl ].

VAR_000624

Natural variant

222

1

E → K in Munster-4. Ref.50

VAR_000625

Experimental info

Sequence conflict

32

1

W → P AA sequence Ref.25

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

267

Helix Strand Turn

Details...

Beta strand

69 – 73

5

Helix

74 – 108

35

Helix

121 – 140

20

Helix

143 – 161

19

Helix

170 – 211

42

Turn

212 – 214

3

Beta strand

215 – 217

3

Helix

220 – 237

18

Beta strand

238 – 240

3

Helix

243 – 266

24

Sequences

	Sequence		Length	Mass (Da)
	P02647 [UniParc]. Last modified July 21, 1986. Version 1. Checksum: 1A28B8366E620310	FASTA	267	30,778
	10 20 30 40 50 60 MKAAVLTLAV LFLTGSQARH FWQQDEPPQS PWDRVKDLAT VYVDVLKDSG RDYVSQFEGS 70 80 90 100 110 120 ALGKQLNLKL LDNWDSVTST FSKLREQLGP VTQEFWDNLE KETEGLRQEM SKDLEEVKAK 130 140 150 160 170 180 VQPYLDDFQK KWQEEMELYR QKVEPLRAEL QEGARQKLHE LQEKLSPLGE EMRDRARAHV 190 200 210 220 230 240 DALRTHLAPY SDELRQRLAA RLEALKENGG ARLAEYHAKA TEHLSTLSEK AKPALEDLRQ 250 260 GLLPVLESFK VSFLSALEEY TKKLNTQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gene structure of human apolipoprotein A1." Shoulders C.C., Kornblihtt A.R., Munro B.S., Baralle F.E. Nucleic Acids Res. 11:2827-2837(1983) [PubMed: 6406984] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Nucleotide sequence of cloned cDNA of human apolipoprotein A-I." Cheung P., Chan L. Nucleic Acids Res. 11:3703-3715(1983) [PubMed: 6304641] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Isolation and characterization of the human apolipoprotein A-I gene." Karathanasis S.K., Zannis V.I., Breslow J.L. Proc. Natl. Acad. Sci. U.S.A. 80:6147-6151(1983) [PubMed: 6413973] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Isolation and DNA sequence of full-length cDNA and of the entire gene for human apolipoprotein AI -- discovery of a new genetic polymorphism in the apo AI gene." Seilhamer J.J., Protter A.A., Frossard P., Levy-Wilson B. DNA 3:309-317(1984) [PubMed: 6207999] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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: 6328445] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Nucleotide sequence and the encoded amino acids of human apolipoprotein A-I mRNA." Law S.W., Brewer H.B. Jr. Proc. Natl. Acad. Sci. U.S.A. 81:66-70(1984) [PubMed: 6198645] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Tangier disease. The complete mRNA sequence encoding for preproapo-A-I." Law S.W., Brewer H.B. Jr. J. Biol. Chem. 260:12810-12814(1985) [PubMed: 2995392] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[8]	"Sequence and expression of Tangier apoA-I gene." Makrides S.C., Ruiz-Opazo N., Hayden M.R., Nussbaum A.L., Breslow J.L., Zannis V.I. Eur. J. Biochem. 173:465-471(1988) [PubMed: 3129297] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (VARIANT TANGIER).
[9]	"Production of human recombinant proapolipoprotein A-I in Escherichia coli: purification and biochemical characterization." Moguilevsky N., Roobol C., Loriau R., Guillaume J.P., Jacobs P., Cravador A., Herzog A., Brouwers L., Scarso A., Gilles P., Holmquist L., Carlson L.A., Bollen A. DNA 8:429-436(1989) [PubMed: 2673706] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[10]	"The effects of scale: variation in the APOA1/C3/A4/A5 gene cluster." Fullerton S.M., Buchanan A.V., Sonpar V.A., Taylor S.L., Smith J.D., Carlson C.S., Salomaa V., Stengaard J.H., Boerwinkle E., Clark A.G., Nickerson D.A., Weiss K.M. Hum. Genet. 115:36-56(2004) [PubMed: 15108119] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-61.
[11]	"Expression of human proapolipoprotein A-1." Bollen A., Gobert J., Wuelfert E. Patent number EP0293357, 30-NOV-1988 Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[12]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[13]	NHLBI resequencing and genotyping service (RS&G) Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[14]	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].
[15]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Skeletal muscle.
[16]	"Human plasma proapoA-I: isolation and amino-terminal sequence." Brewer H.B. Jr., Fairwell T., Kay L., Meng M., Ronan R., Law S., Light J.A. Biochem. Biophys. Res. Commun. 113:626-632(1983) [PubMed: 6409108] [Abstract] Cited for: PROTEIN SEQUENCE OF 19-27.
[17]	"The primary structure of human plasma high density apolipoprotein glutamine I (ApoA-I). II. The amino acid sequence and alignment of cyanogen bromide fragments IV, III, and I." Baker H.N., Gotto A.M. Jr., Jackson R.L. J. Biol. Chem. 250:2725-2738(1975) [PubMed: 164450] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-267.
[18]	"The amino acid sequence of human APOA-I, an apolipoprotein isolated from high density lipoproteins." Brewer H.B. Jr., Fairwell T., Larue A., Ronan R., Houser A., Bronzert T.J. Biochem. Biophys. Res. Commun. 80:623-630(1978) [PubMed: 204308] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-267.
[19]	"Serum prostacyclin stabilizing factor is identical to apolipoprotein A-I (Apo A-I). A novel function of Apo A-I." Yui Y., Aoyama T., Morishita H., Takahashi M., Takatsu Y., Kawai C. J. Clin. Invest. 82:803-807(1988) [PubMed: 3047170] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-56.
[20]	"Identification of apolipoprotein A1 and immunoglobulin as components of a serum complex that mediates activation of human sperm motility." Aakerloef E., Joernvall H., Slotte H., Pousette A. Biochemistry 30:8986-8990(1991) [PubMed: 1909888] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-50, FUNCTION, IDENTIFICATION IN THE SPAP COMPLEX. Tissue: Serum.
[21]	"Apolipoprotein A-I binds to a family of bovine seminal plasma proteins." Manjunath P., Marcel Y.L., Uma J., Seidah N.G., Chretien M., Chapdelaine A. J. Biol. Chem. 264:16853-16857(1989) [PubMed: 2506184] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-48.
[22]	"Similarity of cruzin, an inhibitor of Trypanosoma cruzi neuraminidase, to high-density lipoprotein." Prioli R.P., Ordovas J.M., Rosenberg I., Schaeffer E.J., Pereira M.E.A. Science 238:1417-1419(1987) [PubMed: 3120314] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-43.
[23]	"The human myocardial two-dimensional gel protein database: update 1994." Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J. Electrophoresis 15:1459-1465(1994) [PubMed: 7895732] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-42. Tissue: Heart.
[24]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-34. Tissue: Platelet.
[25]	"The apolipoprotein A-I binding protein of placenta and the SP-40,40 protein of human blood are different proteins which both bind to apolipoprotein A-I." Ehnholm C., Bozas S.E., Tenkanen H., Kirszbaum L., Metso J., Murphy B., Walker I.D. Biochim. Biophys. Acta 1086:255-260(1991) [PubMed: 1742316] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-33, INTERACTION WITH APOA1BP AND CLU.
[26]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 35-64; 70-101; 121-140; 165-173; 185-195 AND 240-263, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[27]	"Isolation and characterization of cDNA clones for human apolipoprotein A-I." Breslow J.L., Ross D., McPherson J., Williams H.W., Kurnit D., Nussbaum A.L., Karathanasis S.K., Zannis V.I. Proc. Natl. Acad. Sci. U.S.A. 79:6861-6865(1982) [PubMed: 6294659] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 118-267.
[28]	"Human apolipoprotein A-I. Post-translational modification by fatty acid acylation." Hoeg J.M., Meng M.S., Ronan R., Fairwell T., Brewer H.B. Jr. J. Biol. Chem. 261:3911-3914(1986) [PubMed: 3005308] [Abstract] Cited for: PALMITOYLATION.
[29]	"Intracellular and extracellular processing of human apolipoprotein A-I: secreted apolipoprotein A-I isoprotein 2 is a propeptide." Zannis V.I., Karathanasis S.K., Keutmann H.T., Goldberger G., Breslow J.L. Proc. Natl. Acad. Sci. U.S.A. 80:2574-2578(1983) [PubMed: 6405383] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[30]	"The preferential site of non-enzymatic glycation of human apolipoprotein A-I in vivo." Calvo C., Ulloa N., Campos M., Verdugo C., Ayrault-Jarrier M. Clin. Chim. Acta 217:193-198(1993) [PubMed: 8261628] [Abstract] Cited for: GLYCATION AT LYS-263.
[31]	"Cloning and characterization of a novel apolipoprotein A-I-binding protein, AI-BP, secreted by cells of the kidney proximal tubules in response to HDL or ApoA-I." Ritter M., Buechler C., Boettcher A., Barlage S., Schmitz-Madry A., Orso E., Bared S.M., Schmiedeknecht G., Baehr C.H., Fricker G., Schmitz G. Genomics 79:693-702(2002) [PubMed: 11991719] [Abstract] Cited for: INTERACTION WITH APOA1BP.
[32]	"Novel mass spectrometric immunoassays for the rapid structural characterization of plasma apolipoproteins." Niederkofler E.E., Tubbs K.A., Kiernan U.A., Nedelkov D., Nelson R.W. J. Lipid Res. 44:630-639(2003) [PubMed: 12562854] [Abstract] Cited for: MASS SPECTROMETRY.
[33]	"NDRG1 interacts with APO A-I and A-II and is a functional candidate for the HDL-C QTL on 8q24." Hunter M., Angelicheva D., Tournev I., Ingley E., Chan D.C., Watts G.F., Kremensky I., Kalaydjieva L. Biochem. Biophys. Res. Commun. 332:982-992(2005) [PubMed: 15922294] [Abstract] Cited for: INTERACTION WITH NDRG1.
[34]	"An initial characterization of the serum phosphoproteome." Zhou W., Ross M.M., Tessitore A., Ornstein D., Vanmeter A., Liotta L.A., Petricoin E.F. III J. Proteome Res. 8:5523-5531(2009) [PubMed: 19824718] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-191, TISSUE SPECIFICITY, MASS SPECTROMETRY. Tissue: Serum.
[35]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[36]	"Conformation of human serum apolipoprotein A-I(166-185) in the presence of sodium dodecyl sulfate or dodecylphosphocholine by 1H-NMR and CD. Evidence for specific peptide-SDS interactions." Wang G., Treleaven W.D., Cushley R.J. Biochim. Biophys. Acta 1301:174-184(1996) [PubMed: 8664326] [Abstract] Cited for: STRUCTURE BY NMR OF 190-209.
[37]	"Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation." Borhani D.W., Rogers D.P., Engler J.A., Brouillette C.G. Proc. Natl. Acad. Sci. U.S.A. 94:12291-12296(1997) [PubMed: 9356442] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 67-267.
[38]	"Autosomal dominant hypoalphalipoproteinemia due to a completely defective apolipoprotein A-I gene." Nakata K., Kobayashi K., Yanagi H., Shimakura Y., Tsuchiya S., Arinami T., Hamaguchi H. Biochem. Biophys. Res. Commun. 196:950-955(1993) [PubMed: 8240372] [Abstract] Cited for: DISEASE.
[39]	"Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia." Ng D.S., Leiter L.A., Vezina C., Connelly P.W., Hegele R.A. J. Clin. Invest. 93:223-229(1994) [PubMed: 8282791] [Abstract] Cited for: DISEASE.
[40]	"Apolipoprotein A-IMilano. Detection of normal A-I in affected subjects and evidence for a cysteine for arginine substitution in the variant A-I." Weisgraber K.H., Rall S.C. Jr., Bersot T.P., Mahley R.W., Franceschini G., Sirtori C.R. J. Biol. Chem. 258:2508-2513(1983) [PubMed: 6401735] [Abstract] Cited for: VARIANT MILANO CYS-197.
[41]	"Tangier disease: defective recombination of a specific Tangier apolipoprotein A-I isoform (pro-apo A-I) with high density lipoproteins." Schmitz G., Assmann G., Rall S.C. Jr., Mahley R.W. Proc. Natl. Acad. Sci. U.S.A. 80:6081-6085(1983) [PubMed: 6412234] [Abstract] Cited for: VARIANT TANGIER.
[42]	"Apolipoprotein A-IGiessen (Pro143-->Arg). A mutant that is defective in activating lecithin:cholesterol acyltransferase." Utermann G., Haas J., Steinmetz A., Paetzold R., Rall S.C. Jr., Weisgraber K.H., Mahley R.W. Eur. J. Biochem. 144:325-331(1984) [PubMed: 6489332] [Abstract] Cited for: VARIANT GIESSEN ARG-167.
[43]	"Abnormal lecithin:cholesterol acyltransferase activation by a human apolipoprotein A-I variant in which a single lysine residue is deleted." Rall S.C. Jr., Weisgraber K.H., Mahley R.W., Ogawa Y., Fielding C.J., Utermann G., Haas J., Steinmetz A., Menzel H.J., Assmann G. J. Biol. Chem. 259:10063-10070(1984) [PubMed: 6432779] [Abstract] Cited for: VARIANT NORWAY LYS-160.
[44]	"Variant apolipoprotein AI as a major constituent of a human hereditary amyloid." Nichols W.C., Dwulet F.E., Liepnieks J., Benson M.D. Biochem. Biophys. Res. Commun. 156:762-768(1988) [PubMed: 3142462] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-107, VARIANT AMYLIOWA ARG-50.
[45]	"A mutation in apolipoprotein A-I in the Iowa type of familial amyloidotic polyneuropathy." Nichols W.C., Gregg R.E., Brewer H.B. Jr., Benson M.D. Genomics 8:318-323(1990) [PubMed: 2123470] [Abstract] Cited for: VARIANT AMYLIOWA ARG-50.
[46]	"Isolation and characterization of human apolipoprotein A-I Fukuoka (110 Glu-->Lys). A novel apolipoprotein variant." Takada Y., Sasaki J., Ogata S., Nakanishi T., Ikehara Y., Arakawa K. Biochim. Biophys. Acta 1043:169-176(1990) [PubMed: 2107878] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-267, VARIANT FUKUOKA LYS-134.
[47]	"Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis." Soutar A.K., Hawkins P.N., Vigushin D.M., Tennent G.A., Booth S.E., Hutton T., Nguyen O., Totty N.F., Feest T.G., Hsuan J.J., Pepys M.B. Proc. Natl. Acad. Sci. U.S.A. 89:7389-7393(1992) [PubMed: 1502149] [Abstract] Cited for: PROTEIN SEQUENCE OF 25-112, VARIANT AMYL8 ARG-84.
[48]	"Apolipoprotein A1 Baltimore (Arg-10-->Leu), a new ApoA1 variant." Ladias J.A.A., Kwiterovich P.O. Jr., Smith H.H., Karathanasis S.K., Antonarakis S.E. Hum. Genet. 84:439-445(1990) [PubMed: 2108924] [Abstract] Cited for: VARIANT BALTIMORE LEU-34.
[49]	"Apolipoprotein A-I variants. Naturally occurring substitutions of proline residues affect plasma concentration of apolipoprotein A-I." von Eckardstein A., Funke H., Henke A., Altland K., Benninghoven A., Assmann G., Welp S., Roetrige A., Kock R. J. Clin. Invest. 84:1722-1730(1989) [PubMed: 2512329] [Abstract] Cited for: VARIANTS ARG-27; ARG-28 AND ARG-189.
[50]	"Structural analysis of human apolipoprotein A-I variants. Amino acid substitutions are nonrandomly distributed throughout the apolipoprotein A-I primary structure." von Eckardstein A., Funke H., Walter M., Altland K., Benninghoven A., Assmann G. J. Biol. Chem. 265:8610-8617(1990) [PubMed: 2111322] [Abstract] Cited for: VARIANTS GLU-113; MET-131; GLY-163; VAL-171 AND LYS-222.
[51]	"Characterization of two new human apolipoprotein A-I variants: apolipoprotein A-I Tsushima (Trp-108-->Arg) and A-I Hita (Ala-95-->Asp)." Araki K., Sasaki J., Matsunaga A., Takada Y., Moriyama K., Hidaka K., Arakawa K. Biochim. Biophys. Acta 1214:272-278(1994) [PubMed: 7918609] [Abstract] Cited for: VARIANTS HITA AND TSUSHIMA.
[52]	"A novel homozygous missense mutation in the apo A-I gene with apo A-I deficiency." Huang W., Sasaki J., Matsunaga A., Nanimatsu H., Moriyama K., Han H., Kugi M., Koga T., Yamaguchi K., Arakawa K. Arterioscler. Thromb. Vasc. Biol. 18:389-396(1998) [PubMed: 9514407] [Abstract] Cited for: VARIANT AOITA GLU-180.
[53]	"Apo A-I Zaragoza(L144R): a novel mutation in the apolipoprotein A-I gene associated with familial hypoalphalipoproteinemia." Recalde D., Cenarro A., Civeira F., Pocovi M. Hum. Mutat. 11:416-416(1998) Cited for: VARIANT ZARAGOZA ARG-168.
[54]	"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: 12966036] [Abstract] Cited for: VARIANT ILE-92.
+	Additional computationally mapped references.

Web resources

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J00098 Genomic DNA. Translation: AAB59514.1.
X01038 Genomic DNA. Translation: CAA25519.1.
X02162 mRNA. Translation: CAA26097.1.
X00566 mRNA. Translation: CAA25232.1.
M11791 mRNA. Translation: AAA35545.1.
X07496 Genomic DNA. Translation: CAA30377.1.
M27875 mRNA. Translation: AAA62829.1.
M29068 mRNA. Translation: AAA51747.1.
AY422952 Genomic DNA. Translation: AAQ91811.1.
AY555191 Genomic DNA. Translation: AAS68227.1.
A14829 mRNA. Translation: CAA01198.1.
AK292231 mRNA. Translation: BAF84920.1.
EF444948 Genomic DNA. Translation: ACA05932.1.
EF444948 Genomic DNA. Translation: ACA05933.1.
EF444948 Genomic DNA. Translation: ACA05934.1.
EF444948 Genomic DNA. Translation: ACA05935.1.
EF444948 Genomic DNA. Translation: ACA05936.1.
CH471065 Genomic DNA. Translation: EAW67274.1.
BC005380 mRNA. Translation: AAH05380.1.
BC110286 mRNA. Translation: AAI10287.1.

IPI

IPI00021841.

PIR

LPHUA1. A90947.

RefSeq

NP_000030.1. NM_000039.1.

UniGene

Hs.93194.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AV1	X-ray	4.00	A/B/C/D	68-267	[»]
1GW3	NMR	-	A	166-211	[»]
1GW4	NMR	-	A	166-211	[»]
1ODP	NMR	-	A	190-209	[»]
1ODQ	NMR	-	A	190-209	[»]
1ODR	NMR	-	A	190-209	[»]
2A01	X-ray	2.40	A/B/C	25-267	[»]
3J00	electron microscopy	-	0/1	68-267	[»]
3K2S	X-ray	-	A/B	25-267	[»]
3R2P	X-ray	2.20	A	25-208	[»]

ProteinModelPortal

P02647.

SMR

P02647. Positions 27-267.

DisProt

DP00386.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29619N.

IntAct

P02647. 54 interactions.

MINT

MINT-5000866.

STRING

P02647.

PTM databases

PhosphoSite

P02647.

Polymorphism databases

DMDM

113992.

2D gel databases

SWISS-2DPAGE

P02647.

Cornea-2DPAGE

P02647.

DOSAC-COBS-2DPAGE

P02647.

OGP

P02647.

PMMA-2DPAGE

P02647.

REPRODUCTION-2DPAGE

IPI00021841.
P02647.

Siena-2DPAGE

P02647.

UCD-2DPAGE

P02647.

Proteomic databases

PeptideAtlas

P02647.

PRIDE

P02647.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000236850; ENSP00000236850; ENSG00000118137.
ENST00000359492; ENSP00000352471; ENSG00000118137.
ENST00000375320; ENSP00000364469; ENSG00000118137.
ENST00000375323; ENSP00000364472; ENSG00000118137.

GeneID

335.

KEGG

hsa:335.

UCSC

uc001ppu.1. human.

Organism-specific databases

CTD

335.

GeneCards

GC11M116706.

HGNC

HGNC:600. APOA1.

HPA

CAB016778.

MIM

105200. phenotype.
107680. gene.
205400. phenotype.
604091. phenotype.

neXtProt

NX_P02647.

Orphanet

425. Apolipoprotein A-I deficiency.
93560. Familial renal amyloidosis due to Apolipoprotein AI variant.
85443. Primary amyloidosis.

PharmGKB

PA49.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20905.

HOGENOM

HBG280675.

HOVERGEN

HBG105708.

InParanoid

P02647.

OMA

YRQKVAP.

OrthoDB

EOG44J2JV.

PhylomeDB

P02647.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.

Reactome

REACT_15518. Transmembrane transport of small molecules.
REACT_22258. Metabolism of lipids and lipoproteins.
REACT_604. Hemostasis.
REACT_75925. Amyloids.

Gene expression databases

ArrayExpress

P02647.

Bgee

P02647.

CleanEx

HS_APOA1.

Genevestigator

P02647.

GermOnline

ENSG00000118137. Homo sapiens.

Family and domain databases

InterPro

IPR013326. ApoA/E_ApoLp.
IPR000074. ApoA1_A4_E.
[Graphical view]

Gene3D

G3DSA:1.20.120.20. ApoA/E_ApoLp. 1 hit.

KO

K08757.

Pfam

PF01442. Apolipoprotein. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

1387.

PMAP-CutDB

P02647.

SOURCE

Search...

Entry information

Entry name

APOA1_HUMAN

Accession

Primary (citable) accession number: P02647
Secondary accession number(s): A8K866 , Q6LDN9, Q6Q785, Q9UCS8, Q9UCT8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 21, 1986
Last modified:	January 25, 2012
This is version 167 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.