LPA lipoprotein, Lp(a) [Homo sapiens] - Gene

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Summary

Official Symbol: LPAprovided by HGNC
Official Full Name: lipoprotein, Lp(a)provided by HGNC
Primary source: HGNC:6667
See related: Ensembl:ENSG00000198670; HPRD:01063; MIM:152200; Vega:OTTHUMG00000015956
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LP; AK38; APOA
Summary: The protein encoded by this gene is a serine proteinase that inhibits the activity of tissue-type plasminogen activator I. The encoded protein constitutes a substantial portion of lipoprotein(a) and is proteolytically cleaved, resulting in fragments that attach to atherosclerotic lesions and promote thrombogenesis. Elevated plasma levels of this protein are linked to atherosclerosis. Depending on the individual, the encoded protein contains 2-43 copies of kringle-type domains. The allele represented here contains 15 copies of the kringle-type repeats and corresponds to that found in the reference genome sequence. [provided by RefSeq, Dec 2009]

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Genomic context

Location :: 6q26

Sequence :: Chromosome: 6; NC_000006.11 (160952515..161087407, complement)

See LPA in Epigenomics, MapViewer

Chromosome 6 - NC_000006.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

investigation of role in atherogenesis played by oxLp(a): Serum oxLp(a) may be more closely associated with accelerated carotid atherosclerosis, in comparison to serum Lp(a), in asymptomatic middle-aged/older subjects in Japan.
Title: The relationship between oxidized lipoprotein(a) and carotid atherosclerosis in asymptomatic subjects: a comparison with native lipoprotein(a).
The current study suggests evidence of high Lp(a) concentrations in childhood migraine; perhaps a novel link exists between migraine and stroke.
Title: Lipoprotein a levels in pediatric migraine.
In hemodialysis patients, OxPL/apoB, lipoprotein(a) and OxLDL biomarkers are not associated with cardiovascular disease.
Title: OxPL/apoB, lipoprotein(a) and OxLDL biomarkers and cardiovascular disease in chronic hemodialysis patients.
Meta-analysis: revealed no candidate genes from the HumanCVD BeadChip outside the LPA locus to have an effect on Lp(a) levels.
Title: Meta analysis of candidate gene variants outside the LPA locus with Lp(a) plasma levels in 14,500 participants of six White European cohorts.
Lp(a) measurements may have a role in risk stratification in cardiovascular disease of Southeast Asians.
Title: Abnormal lipoprotein(a) levels predict coronary artery calcification in Southeast Asians but not in Caucasians: use of noninvasive imaging for evaluation of an emerging risk factor.
beta-GPI-Lp(a) complex concentrations increased in active RA. Inflammation and oxidative stress in RA contribute to the increase of ox-Lp(a) and subsequently the formation of beta-GPI-Lp(a).
Title: Increased serum levels of β₂-GPI-Lp(a) complexes and their association with premature atherosclerosis in patients with rheumatoid arthritis.
Healthy young men with positive parental history of premature myocardial infarction have a similar Lp(a) levels but worse lipid profile than women.
Title: Lipoprotein(a) concentration does not differ between sexes in healthy offspring of patients with premature myocardial infarction.
demonstrated differential immunoexpression patterns between native Lp(a) and plasminogen, and suggested that Lp(a)-plasminogen interaction may play a part in differential mechanisms in all atherosclerotic lesions of carotid and cerebral arteries
Title: Differential expression of oxidized/native lipoprotein(a) and plasminogen in human carotid and cerebral artery plaques.
an unbiased genome-wide admixture scan for frequency-differentiated genetic determinants of Lp(a) level in African Americans
Title: Single-nucleotide polymorphisms in LPA explain most of the ancestry-specific variation in Lp(a) levels in African Americans.
no support for early atherogenic effects of increased Lp(a) levels
Title: Conventional and Mendelian randomization analyses suggest no association between lipoprotein(a) and early atherosclerosis: the Young Finns Study.

Submit: New GeneRIF Correction See all (112)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

A genome-wide association study identifies protein quantitative trait loci (pQTLs).

Genetic and clinical correlates of early-outgrowth colony-forming units.

Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q.

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

Novel association to the proprotein convertase PCSK7 gene locus revealed by analysing soluble transferrin receptor (sTfR) levels.

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Products	Interactant	Other Gene	Source	Pubs	Description
P08519	P02749	APOH	HPRD	PubMed
P08519	P27824	CANX	HPRD	PubMed
P08519	Q9UNI1	CELA1	HPRD	PubMed
P08519	P08246	ELANE	HPRD	PubMed
P08519	Q9UBX5	FBLN5	HPRD	PubMed
P08519	P02675	FGB	HPRD	PubMed
P08519	P02751	FN1	HPRD	PubMed
P08519	P98164	LRP2	HPRD	PubMed
P08519	P39900	MMP12	HPRD	PubMed
BioGRID:110202	BioGRID:107271	CANX	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110202	BioGRID:108535	FGB	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110202	BioGRID:108621	FN1	BioGRID	PubMed	Biochemical Activity; Reconstituted Complex
BioGRID:110202	BioGRID:110216	LRP2	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
apolipoprotein binding	IPI Inferred from Physical Interaction more info	PubMed
endopeptidase inhibitor activity	TAS Traceable Author Statement more info	PubMed
fibronectin binding	IPI Inferred from Physical Interaction more info	PubMed
heparin binding	NAS Non-traceable Author Statement more info	PubMed
peptidase activity	IEA Inferred from Electronic Annotation more info
serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
blood circulation	TAS Traceable Author Statement more info	PubMed
lipid metabolic process	TAS Traceable Author Statement more info
lipid transport	IEA Inferred from Electronic Annotation more info
lipoprotein metabolic process	TAS Traceable Author Statement more info
negative regulation of endopeptidase activity	TAS Traceable Author Statement more info	PubMed
proteolysis	IEA Inferred from Electronic Annotation more info
receptor-mediated endocytosis	TAS Traceable Author Statement more info
small molecule metabolic process	TAS Traceable Author Statement more info
transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
extracellular region	NAS Non-traceable Author Statement more info	PubMed
extracellular region	TAS Traceable Author Statement more info
plasma lipoprotein particle	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: apolipoprotein(a)

Names: apolipoprotein(a); lp(a); apo(a); antiangiogenic AK38 protein

NP_005568.2

EC 3.4.21.-

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016147.1 RefSeqGene

Range

5001..139893

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005577.2 → NP_005568.2 apolipoprotein(a) precursor

Status: REVIEWED

Source sequence(s)

AL109933, AL596089

Consensus CDS

CCDS43523.1

UniProtKB/Swiss-Prot

P08519

Related

ENSP00000321334, OTTHUMP00000017543, ENST00000316300, OTTHUMT00000042957

Conserved Domains (2) summary

cd00108
Location:1614 – 1694
Blast Score: 291

KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...

cd00190
Location:1820 – 2034
Blast Score: 651

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000006.11 Reference GRCh37.p5 Primary Assembly

Range

160952515..161087407, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000138.1 Alternate HuRef

Range

158427443..158508764, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF158656.1	AAF03677.1
genomic	AF158657.1	AAF03676.1
genomic	AF158661.1	AAF03679.1
genomic	AF158663.1	AAF03680.1
genomic	AL109933.25	CAI22905.1
genomic	AL596089.19	CAH73590.1
genomic	CH471051.2	EAW47596.1
genomic	DQ452068.1	ABF47086.1
mRNA	AY039748.1	AAK74187.1
mRNA	X06290.1	CAA29618.1

Protein Accession	Links
Protein Accession	GenePept Link	UniProtKB Link
P08519.1	GenPept	UniProtKB/Swiss-Prot:P08519
Q1HP67	GenPept	UniProtKB/TrEMBL:Q1HP67
Q8N696	GenPept	UniProtKB/TrEMBL:Q8N696
Q9UIR5	GenPept	UniProtKB/TrEMBL:Q9UIR5
Q9UIR6	GenPept	UniProtKB/TrEMBL:Q9UIR6
Q9UIR8	GenPept	UniProtKB/TrEMBL:Q9UIR8
Q9UKJ7	GenPept	UniProtKB/TrEMBL:Q9UKJ7