LPA

Protein identityUniProt · HPA

UniProt accession

P08519

Gene

LPA

Ensembl

ENSG00000198670

Chromosome

6

Canonical length

2040 aa

Protein class

Candidate cardiovascular disease genes, Enzymes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

2040 residues, UniProt reviewed canonical sequence.

>P08519|LPA
     1  MEHKEVVLLL LLFLKSAAPE QSHVVQDCYH GDGQSYRGTY STTVTGRTCQ AWSSMTPHQH
    61  NRTTENYPNA GLIMNYCRNP DAVAAPYCYT RDPGVRWEYC NLTQCSDAEG TAVAPPTVTP
   121  VPSLEAPSEQ APTEQRPGVQ ECYHGNGQSY RGTYSTTVTG RTCQAWSSMT PHSHSRTPEY
   181  YPNAGLIMNY CRNPDAVAAP YCYTRDPGVR WEYCNLTQCS DAEGTAVAPP TVTPVPSLEA
   241  PSEQAPTEQR PGVQECYHGN GQSYRGTYST TVTGRTCQAW SSMTPHSHSR TPEYYPNAGL
   301  IMNYCRNPDA VAAPYCYTRD PGVRWEYCNL TQCSDAEGTA VAPPTVTPVP SLEAPSEQAP
   361  TEQRPGVQEC YHGNGQSYRG TYSTTVTGRT CQAWSSMTPH SHSRTPEYYP NAGLIMNYCR
   421  NPDAVAAPYC YTRDPGVRWE YCNLTQCSDA EGTAVAPPTV TPVPSLEAPS EQAPTEQRPG
   481  VQECYHGNGQ SYRGTYSTTV TGRTCQAWSS MTPHSHSRTP EYYPNAGLIM NYCRNPDAVA
   541  APYCYTRDPG VRWEYCNLTQ CSDAEGTAVA PPTVTPVPSL EAPSEQAPTE QRPGVQECYH
   601  GNGQSYRGTY STTVTGRTCQ AWSSMTPHSH SRTPEYYPNA GLIMNYCRNP DAVAAPYCYT
   661  RDPGVRWEYC NLTQCSDAEG TAVAPPTVTP VPSLEAPSEQ APTEQRPGVQ ECYHGNGQSY
   721  RGTYSTTVTG RTCQAWSSMT PHSHSRTPEY YPNAGLIMNY CRNPDAVAAP YCYTRDPGVR
   781  WEYCNLTQCS DAEGTAVAPP TVTPVPSLEA PSEQAPTEQR PGVQECYHGN GQSYRGTYST
   841  TVTGRTCQAW SSMTPHSHSR TPEYYPNAGL IMNYCRNPDP VAAPYCYTRD PSVRWEYCNL
   901  TQCSDAEGTA VAPPTITPIP SLEAPSEQAP TEQRPGVQEC YHGNGQSYQG TYFITVTGRT
   961  CQAWSSMTPH SHSRTPAYYP NAGLIKNYCR NPDPVAAPWC YTTDPSVRWE YCNLTRCSDA
  1021  EWTAFVPPNV ILAPSLEAFF EQALTEETPG VQDCYYHYGQ SYRGTYSTTV TGRTCQAWSS
  1081  MTPHQHSRTP ENYPNAGLTR NYCRNPDAEI RPWCYTMDPS VRWEYCNLTQ CLVTESSVLA
  1141  TLTVVPDPST EASSEEAPTE QSPGVQDCYH GDGQSYRGSF STTVTGRTCQ SWSSMTPHWH
  1201  QRTTEYYPNG GLTRNYCRNP DAEISPWCYT MDPNVRWEYC NLTQCPVTES SVLATSTAVS
  1261  EQAPTEQSPT VQDCYHGDGQ SYRGSFSTTV TGRTCQSWSS MTPHWHQRTT EYYPNGGLTR
  1321  NYCRNPDAEI RPWCYTMDPS VRWEYCNLTQ CPVMESTLLT TPTVVPVPST ELPSEEAPTE
  1381  NSTGVQDCYR GDGQSYRGTL STTITGRTCQ SWSSMTPHWH RRIPLYYPNA GLTRNYCRNP
  1441  DAEIRPWCYT MDPSVRWEYC NLTRCPVTES SVLTTPTVAP VPSTEAPSEQ APPEKSPVVQ
  1501  DCYHGDGRSY RGISSTTVTG RTCQSWSSMI PHWHQRTPEN YPNAGLTENY CRNPDSGKQP
  1561  WCYTTDPCVR WEYCNLTQCS ETESGVLETP TVVPVPSMEA HSEAAPTEQT PVVRQCYHGN
  1621  GQSYRGTFST TVTGRTCQSW SSMTPHRHQR TPENYPNDGL TMNYCRNPDA DTGPWCFTMD
  1681  PSIRWEYCNL TRCSDTEGTV VAPPTVIQVP SLGPPSEQDC MFGNGKGYRG KKATTVTGTP
  1741  CQEWAAQEPH RHSTFIPGTN KWAGLEKNYC RNPDGDINGP WCYTMNPRKL FDYCDIPLCA
  1801  SSSFDCGKPQ VEPKKCPGSI VGGCVAHPHS WPWQVSLRTR FGKHFCGGTL ISPEWVLTAA
  1861  HCLKKSSRPS SYKVILGAHQ EVNLESHVQE IEVSRLFLEP TQADIALLKL SRPAVITDKV
  1921  MPACLPSPDY MVTARTECYI TGWGETQGTF GTGLLKEAQL LVIENEVCNH YKYICAEHLA
  1981  RGTDSCQGDS GGPLVCFEKD KYILQGVTSW GLGCARPNKP GVYARVSRFV TWIEGMMRNN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LPA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

72 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LPA.

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 322 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Lipoprotein(a) deficiency, congenital
• LIPOPROTEIN(a) QUANTITATIVE TRAIT LOCUS

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.52

gnomAD pLI

0

gnomAD missense Z

-3.27

DepMap mean gene effect

-0.23

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood circulation
• lipid metabolic process
• lipid transport
• proteolysis

Molecular functions

• apolipoprotein binding
• endopeptidase inhibitor activity
• fibronectin binding
• heparin binding
• serine-type endopeptidase activity

Cellular components

• extracellular region
• plasma lipoprotein particle

Protein domainsUniProt · Pfam · InterPro

• Kringle
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• Peptidase S1, PA clan
• Kringle-like fold
• Kringle, conserved site
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Kringle superfamily
• Serine proteases and regulators with kringle domains
• Kringle domain
• Trypsin

KeywordsUniProt

• Atherosclerosis
• Autocatalytic cleavage
• Disulfide bond
• Glycoprotein
• Hydrolase
• Kringle
• Lipid transport
• Protease
• Repeat
• Serine protease
• Signal
• Transport

InteractionsUniProt · HPA

Protein binding partners of LPA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FN1