APOA_HUMAN
ID APOA_HUMAN Reviewed; 2040 AA.
AC P08519; Q5VTD7; Q9UD88;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Apolipoprotein(a);
DE Short=Apo(a);
DE Short=Lp(a);
DE EC=3.4.21.-;
DE Flags: Precursor;
GN Name=LPA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND POLYMORPHISM.
RX PubMed=3670400; DOI=10.1038/330132a0;
RA McLean J.W., Tomlison J.E., Kuang W.-J., Eaton D.L., Chen E.Y., Fless G.M.,
RA Scanu A.M., Lawn R.M.;
RT "cDNA sequence of human apolipoprotein(a) is homologous to plasminogen.";
RL Nature 330:132-137(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND POLYMORPHISM.
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1676-1700.
RC TISSUE=Lymphocyte;
RX PubMed=7848387; DOI=10.1016/0925-4439(93)90130-s;
RA Pfaffinger D., Mc Lean J., Scanu A.M.;
RT "Amplification of human APO(a) kringle 4-37 from blood lymphocyte DNA.";
RL Biochim. Biophys. Acta 1225:107-109(1993).
RN [4]
RP FUNCTION AS A SERINE PROTEASE.
RX PubMed=2531657; DOI=10.1002/j.1460-2075.1989.tb08586.x;
RA Salonen E.-M., Jauhiainen M., Zardi L., Vaheri A., Ehnholm C.;
RT "Lipoprotein(a) binds to fibronectin and has serine proteinase activity
RT capable of cleaving it.";
RL EMBO J. 8:4035-4040(1989).
RN [5]
RP REVIEW.
RX PubMed=2530631; DOI=10.1126/science.2530631;
RA Utermann G.;
RT "The mysteries of lipoprotein(a).";
RL Science 246:904-910(1989).
RN [6]
RP STRUCTURE OF N-LINKED AND O-LINKED CARBOHYDRATES, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=11294842; DOI=10.1074/jbc.m102150200;
RA Garner B., Merry A.H., Royle L., Harvey D.J., Rudd P.M., Thillet J.;
RT "Structural elucidation of the N- and O-glycans of human apolipoprotein(a):
RT role of o-glycans in conferring protease resistance.";
RL J. Biol. Chem. 276:22200-22208(2001).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1613-1700.
RX PubMed=8642595; DOI=10.1006/jmbi.1996.0122;
RA Mikol V., Lograsso P.V., Boettcher B.R.;
RT "Crystal structures of apolipoprotein(a) kringle IV37 free and complexed
RT with 6-aminohexanoic acid and with p-aminomethylbenzoic acid: existence of
RT novel and expected binding modes.";
RL J. Mol. Biol. 256:751-761(1996).
RN [9]
RP VARIANT ARG-1685.
RX PubMed=7918682; DOI=10.1016/0925-4439(94)90104-x;
RA Scanu A.M., Pfaffinger D., Lee J.C., Hinman J.;
RT "A single point mutation (Trp72-->Arg) in human apo(a) kringle 4-37
RT associated with a lysine binding defect in Lp(a).";
RL Biochim. Biophys. Acta 1227:41-45(1994).
CC -!- FUNCTION: Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It
CC has serine proteinase activity and is able of autoproteolysis. Inhibits
CC tissue-type plasminogen activator 1. Lp(a) may be a ligand for
CC megalin/Gp 330. {ECO:0000269|PubMed:2531657}.
CC -!- SUBUNIT: Disulfide-linked to apo-B100. Binds to fibronectin and
CC decorin.
CC -!- INTERACTION:
CC P08519; P02749: APOH; NbExp=4; IntAct=EBI-9232288, EBI-2114682;
CC P08519; P02751: FN1; NbExp=2; IntAct=EBI-9232288, EBI-1220319;
CC -!- PTM: N- and O-glycosylated. The N-glycans are complex biantennary
CC structures present in either a mono- or disialylated state. The O-
CC glycans are mostly (80%) represented by the monosialylated core type I
CC structure, NeuNAcalpha2-3Galbeta1-3GalNAc, with smaller amounts of
CC disialylated and non-sialylated O-glycans also detected.
CC {ECO:0000269|PubMed:11294842}.
CC -!- POLYMORPHISM: LPA genetic variants, including variations in the number
CC of Kringle domains, define the lipoprotein(a) quantitative trait locus
CC (LPAQTL) and influence lipoprotein(a) levels in plasma [MIM:618807].
CC Depending on the individual, the encoded protein contains 2-43 copies
CC of kringle IV-2 repeats. Often the assignement of amino acids in
CC lipoprotein(a) is based on a long allele that contains 37 copies of the
CC kringle-type repeats (PubMed:3670400). The reference allele represented
CC here contains 15 copies of the kringle-type repeats.
CC {ECO:0000269|PubMed:14574404, ECO:0000269|PubMed:3670400}.
CC -!- MISCELLANEOUS: Apo(a) is known to be proteolytically cleaved, leading
CC to the formation of the so-called mini-Lp(a). Apo(a) fragments
CC accumulate in atherosclerotic lesions, where they may promote
CC thrombogenesis. O-glycosylation may limit the extent of proteolytic
CC fragmentation. Homology with plasminogen kringles IV and V is thought
CC to underlie the atherogenicity of the protein, because the fragments
CC are competing with plasminogen for fibrin(ogen) binding.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Plasminogen subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
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DR EMBL; X06290; CAA29618.1; -; mRNA.
DR EMBL; AL109933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL596089; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS43523.1; -.
DR PIR; S00657; S00657.
DR PDB; 1I71; X-ray; 1.45 A; A=1273-1355.
DR PDB; 1JFN; NMR; -; A=1157-1262.
DR PDB; 1KIV; X-ray; 2.10 A; A=1616-1693.
DR PDB; 2FEB; NMR; -; A=1377-1472.
DR PDB; 3KIV; X-ray; 1.80 A; A=1615-1693.
DR PDB; 4BV5; X-ray; 2.10 A; A/B=1615-1693.
DR PDB; 4BV7; X-ray; 1.70 A; A=1615-1693.
DR PDB; 4BVC; X-ray; 1.60 A; A=1615-1693.
DR PDB; 4BVD; X-ray; 1.68 A; A=1615-1693.
DR PDB; 4BVV; X-ray; 1.80 A; A=1719-1799.
DR PDB; 4BVW; X-ray; 2.00 A; A/B=1273-1351.
DR PDB; 4KIV; X-ray; 2.20 A; A=1615-1693.
DR PDB; 6RX7; X-ray; 1.63 A; A/B/C=701-796.
DR PDBsum; 1I71; -.
DR PDBsum; 1JFN; -.
DR PDBsum; 1KIV; -.
DR PDBsum; 2FEB; -.
DR PDBsum; 3KIV; -.
DR PDBsum; 4BV5; -.
DR PDBsum; 4BV7; -.
DR PDBsum; 4BVC; -.
DR PDBsum; 4BVD; -.
DR PDBsum; 4BVV; -.
DR PDBsum; 4BVW; -.
DR PDBsum; 4KIV; -.
DR PDBsum; 6RX7; -.
DR IntAct; P08519; 3.
DR MINT; P08519; -.
DR STRING; 9606.ENSP00000321334; -.
DR DrugBank; DB00513; Aminocaproic acid.
DR DrugBank; DB11886; Infigratinib.
DR DrugBank; DB00877; Sirolimus.
DR MEROPS; S01.999; -.
DR GlyConnect; 56; 21 N-Linked glycans (4 sites), 4 O-Linked glycans.
DR GlyGen; P08519; 59 sites, 21 N-linked glycans (5 sites), 10 O-linked glycans (17 sites).
DR iPTMnet; P08519; -.
DR PhosphoSitePlus; P08519; -.
DR BioMuta; LPA; -.
DR DMDM; 114062; -.
DR CPTAC; non-CPTAC-2621; -.
DR CPTAC; non-CPTAC-2622; -.
DR jPOST; P08519; -.
DR MassIVE; P08519; -.
DR PaxDb; P08519; -.
DR PeptideAtlas; P08519; -.
DR PRIDE; P08519; -.
DR ProteomicsDB; 52116; -.
DR Antibodypedia; 9009; 303 antibodies from 28 providers.
DR Ensembl; ENST00000316300.10; ENSP00000321334.6; ENSG00000198670.12.
DR MANE-Select; ENST00000316300.10; ENSP00000321334.6; NM_005577.4; NP_005568.2.
DR UCSC; uc063sqy.1; human.
DR GeneCards; LPA; -.
DR HGNC; HGNC:6667; LPA.
DR HPA; ENSG00000198670; Tissue enriched (liver).
DR MalaCards; LPA; -.
DR MIM; 152200; gene.
DR MIM; 618807; phenotype.
DR neXtProt; NX_P08519; -.
DR OpenTargets; ENSG00000198670; -.
DR PharmGKB; PA30432; -.
DR VEuPathDB; HostDB:ENSG00000198670; -.
DR eggNOG; ENOG502QVNP; Eukaryota.
DR GeneTree; ENSGT00940000157183; -.
DR HOGENOM; CLU_233276_0_0_1; -.
DR TreeFam; TF329901; -.
DR PathwayCommons; P08519; -.
DR Reactome; R-HSA-8964041; LDL remodeling.
DR SignaLink; P08519; -.
DR ChiTaRS; LPA; human.
DR EvolutionaryTrace; P08519; -.
DR Pharos; P08519; Tbio.
DR PRO; PR:P08519; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P08519; protein.
DR Bgee; ENSG00000198670; Expressed in liver and 80 other tissues.
DR ExpressionAtlas; P08519; baseline and differential.
DR Genevisible; P08519; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IBA:GO_Central.
DR GO; GO:0034358; C:plasma lipoprotein particle; IDA:BHF-UCL.
DR GO; GO:0034185; F:apolipoprotein binding; IPI:BHF-UCL.
DR GO; GO:0004175; F:endopeptidase activity; IBA:GO_Central.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR GO; GO:0001968; F:fibronectin binding; IPI:BHF-UCL.
DR GO; GO:0008201; F:heparin binding; NAS:BHF-UCL.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR GO; GO:0006629; P:lipid metabolic process; NAS:ProtInc.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd00108; KR; 16.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 1.
DR Gene3D; 2.40.20.10; -; 16.
DR InterPro; IPR000001; Kringle.
DR InterPro; IPR013806; Kringle-like.
DR InterPro; IPR018056; Kringle_CS.
DR InterPro; IPR038178; Kringle_sf.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00051; Kringle; 16.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00130; KR; 16.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57440; SSF57440; 16.
DR PROSITE; PS00021; KRINGLE_1; 38.
DR PROSITE; PS50070; KRINGLE_2; 38.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Atherosclerosis; Autocatalytic cleavage; Disulfide bond;
KW Glycoprotein; Hydrolase; Kringle; Lipid transport; Protease;
KW Reference proteome; Repeat; Serine protease; Signal; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..2040
FT /note="Apolipoprotein(a)"
FT /evidence="ECO:0000255"
FT /id="PRO_0000455008"
FT DOMAIN 27..105
FT /note="Kringle 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 141..219
FT /note="Kringle 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 255..333
FT /note="Kringle 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 369..447
FT /note="Kringle 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 483..561
FT /note="Kringle 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 597..675
FT /note="Kringle 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 711..789
FT /note="Kringle 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 825..903
FT /note="Kringle 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 939..1017
FT /note="Kringle 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 1053..1131
FT /note="Kringle 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 1167..1245
FT /note="Kringle 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 1273..1351
FT /note="Kringle 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 1387..1465
FT /note="Kringle 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 1501..1579
FT /note="Kringle 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 1615..1693
FT /note="Kringle 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 1719..1799
FT /note="Kringle 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DOMAIN 1820..2038
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 1147..1166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1365..1388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1476..1497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1147..1161
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1861
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 1904
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 1990
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 557
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 671
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 785
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 899
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1013
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1347
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1381
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1461
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1575
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1689
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 28..105
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 49..88
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 77..100
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 142..219
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 163..202
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 191..214
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 256..333
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 277..316
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 305..328
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 370..447
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 391..430
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 419..442
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 484..561
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 505..544
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 533..556
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 598..675
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 619..658
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 647..670
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 712..789
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 733..772
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 761..784
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 826..903
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 847..886
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 875..898
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 940..1017
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 961..1000
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 989..1012
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1054..1131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1075..1114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1103..1126
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1168..1245
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1189..1228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1217..1240
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1274..1351
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1295..1334
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1323..1346
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1388..1465
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1409..1448
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1437..1460
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1502..1579
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1523..1562
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1551..1574
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1616..1693
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1637..1676
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1665..1688
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1720..1799
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1741..1782
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1770..1794
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00121"
FT DISULFID 1846..1862
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 1938..1996
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 1968..1975
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT DISULFID 1986..2014
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT VARIANT 990
FT /note="R -> Q (in dbSNP:rs41259144)"
FT /id="VAR_047293"
FT VARIANT 1358
FT /note="L -> V (in dbSNP:rs7765803)"
FT /id="VAR_047294"
FT VARIANT 1372
FT /note="L -> V (in dbSNP:rs7765781)"
FT /id="VAR_047295"
FT VARIANT 1399
FT /note="T -> P (in dbSNP:rs41272110)"
FT /id="VAR_047296"
FT VARIANT 1421
FT /note="R -> Q (in dbSNP:rs41272112)"
FT /id="VAR_047297"
FT VARIANT 1598
FT /note="M -> T (in dbSNP:rs41264308)"
FT /id="VAR_047298"
FT VARIANT 1679
FT /note="M -> T (in dbSNP:rs1801693)"
FT /id="VAR_047299"
FT VARIANT 1685
FT /note="W -> R (loss of lysine-sepharose binding)"
FT /evidence="ECO:0000269|PubMed:7918682"
FT /id="VAR_006633"
FT VARIANT 1822
FT /note="G -> A (in dbSNP:rs41265936)"
FT /id="VAR_047300"
FT VARIANT 1891
FT /note="I -> M (in dbSNP:rs3798220)"
FT /id="VAR_047301"
FT VARIANT 2016
FT /note="R -> C (in dbSNP:rs3124784)"
FT /id="VAR_047302"
FT STRAND 712..714
FT /evidence="ECO:0007829|PDB:6RX7"
FT TURN 748..750
FT /evidence="ECO:0007829|PDB:6RX7"
FT STRAND 771..776
FT /evidence="ECO:0007829|PDB:6RX7"
FT STRAND 781..785
FT /evidence="ECO:0007829|PDB:6RX7"
FT HELIX 789..792
FT /evidence="ECO:0007829|PDB:6RX7"
FT STRAND 1157..1159
FT /evidence="ECO:0007829|PDB:1JFN"
FT TURN 1171..1175
FT /evidence="ECO:0007829|PDB:1JFN"
FT STRAND 1196..1198
FT /evidence="ECO:0007829|PDB:1JFN"
FT HELIX 1204..1206
FT /evidence="ECO:0007829|PDB:1JFN"
FT TURN 1208..1210
FT /evidence="ECO:0007829|PDB:1JFN"
FT STRAND 1227..1232
FT /evidence="ECO:0007829|PDB:1JFN"
FT STRAND 1237..1241
FT /evidence="ECO:0007829|PDB:1JFN"
FT STRAND 1274..1276
FT /evidence="ECO:0007829|PDB:4BVW"
FT STRAND 1302..1304
FT /evidence="ECO:0007829|PDB:4BVW"
FT TURN 1310..1312
FT /evidence="ECO:0007829|PDB:1I71"
FT TURN 1314..1317
FT /evidence="ECO:0007829|PDB:1I71"
FT STRAND 1326..1328
FT /evidence="ECO:0007829|PDB:1I71"
FT STRAND 1333..1338
FT /evidence="ECO:0007829|PDB:1I71"
FT STRAND 1343..1347
FT /evidence="ECO:0007829|PDB:1I71"
FT STRAND 1381..1385
FT /evidence="ECO:0007829|PDB:2FEB"
FT STRAND 1404..1406
FT /evidence="ECO:0007829|PDB:2FEB"
FT STRAND 1416..1418
FT /evidence="ECO:0007829|PDB:2FEB"
FT STRAND 1443..1445
FT /evidence="ECO:0007829|PDB:2FEB"
FT STRAND 1616..1618
FT /evidence="ECO:0007829|PDB:4BV7"
FT STRAND 1621..1623
FT /evidence="ECO:0007829|PDB:1KIV"
FT STRAND 1644..1646
FT /evidence="ECO:0007829|PDB:3KIV"
FT TURN 1652..1654
FT /evidence="ECO:0007829|PDB:4BVC"
FT TURN 1656..1659
FT /evidence="ECO:0007829|PDB:3KIV"
FT STRAND 1675..1680
FT /evidence="ECO:0007829|PDB:4BVC"
FT STRAND 1685..1689
FT /evidence="ECO:0007829|PDB:4BVC"
FT STRAND 1748..1750
FT /evidence="ECO:0007829|PDB:4BVV"
FT STRAND 1753..1755
FT /evidence="ECO:0007829|PDB:4BVV"
FT TURN 1757..1759
FT /evidence="ECO:0007829|PDB:4BVV"
FT STRAND 1781..1785
FT /evidence="ECO:0007829|PDB:4BVV"
FT STRAND 1791..1793
FT /evidence="ECO:0007829|PDB:4BVV"
SQ SEQUENCE 2040 AA; 226546 MW; AC7D76CE0A0358CD CRC64;
MEHKEVVLLL LLFLKSAAPE QSHVVQDCYH GDGQSYRGTY STTVTGRTCQ AWSSMTPHQH
NRTTENYPNA GLIMNYCRNP DAVAAPYCYT RDPGVRWEYC NLTQCSDAEG TAVAPPTVTP
VPSLEAPSEQ APTEQRPGVQ ECYHGNGQSY RGTYSTTVTG RTCQAWSSMT PHSHSRTPEY
YPNAGLIMNY CRNPDAVAAP YCYTRDPGVR WEYCNLTQCS DAEGTAVAPP TVTPVPSLEA
PSEQAPTEQR PGVQECYHGN GQSYRGTYST TVTGRTCQAW SSMTPHSHSR TPEYYPNAGL
IMNYCRNPDA VAAPYCYTRD PGVRWEYCNL TQCSDAEGTA VAPPTVTPVP SLEAPSEQAP
TEQRPGVQEC YHGNGQSYRG TYSTTVTGRT CQAWSSMTPH SHSRTPEYYP NAGLIMNYCR
NPDAVAAPYC YTRDPGVRWE YCNLTQCSDA EGTAVAPPTV TPVPSLEAPS EQAPTEQRPG
VQECYHGNGQ SYRGTYSTTV TGRTCQAWSS MTPHSHSRTP EYYPNAGLIM NYCRNPDAVA
APYCYTRDPG VRWEYCNLTQ CSDAEGTAVA PPTVTPVPSL EAPSEQAPTE QRPGVQECYH
GNGQSYRGTY STTVTGRTCQ AWSSMTPHSH SRTPEYYPNA GLIMNYCRNP DAVAAPYCYT
RDPGVRWEYC NLTQCSDAEG TAVAPPTVTP VPSLEAPSEQ APTEQRPGVQ ECYHGNGQSY
RGTYSTTVTG RTCQAWSSMT PHSHSRTPEY YPNAGLIMNY CRNPDAVAAP YCYTRDPGVR
WEYCNLTQCS DAEGTAVAPP TVTPVPSLEA PSEQAPTEQR PGVQECYHGN GQSYRGTYST
TVTGRTCQAW SSMTPHSHSR TPEYYPNAGL IMNYCRNPDP VAAPYCYTRD PSVRWEYCNL
TQCSDAEGTA VAPPTITPIP SLEAPSEQAP TEQRPGVQEC YHGNGQSYQG TYFITVTGRT
CQAWSSMTPH SHSRTPAYYP NAGLIKNYCR NPDPVAAPWC YTTDPSVRWE YCNLTRCSDA
EWTAFVPPNV ILAPSLEAFF EQALTEETPG VQDCYYHYGQ SYRGTYSTTV TGRTCQAWSS
MTPHQHSRTP ENYPNAGLTR NYCRNPDAEI RPWCYTMDPS VRWEYCNLTQ CLVTESSVLA
TLTVVPDPST EASSEEAPTE QSPGVQDCYH GDGQSYRGSF STTVTGRTCQ SWSSMTPHWH
QRTTEYYPNG GLTRNYCRNP DAEISPWCYT MDPNVRWEYC NLTQCPVTES SVLATSTAVS
EQAPTEQSPT VQDCYHGDGQ SYRGSFSTTV TGRTCQSWSS MTPHWHQRTT EYYPNGGLTR
NYCRNPDAEI RPWCYTMDPS VRWEYCNLTQ CPVMESTLLT TPTVVPVPST ELPSEEAPTE
NSTGVQDCYR GDGQSYRGTL STTITGRTCQ SWSSMTPHWH RRIPLYYPNA GLTRNYCRNP
DAEIRPWCYT MDPSVRWEYC NLTRCPVTES SVLTTPTVAP VPSTEAPSEQ APPEKSPVVQ
DCYHGDGRSY RGISSTTVTG RTCQSWSSMI PHWHQRTPEN YPNAGLTENY CRNPDSGKQP
WCYTTDPCVR WEYCNLTQCS ETESGVLETP TVVPVPSMEA HSEAAPTEQT PVVRQCYHGN
GQSYRGTFST TVTGRTCQSW SSMTPHRHQR TPENYPNDGL TMNYCRNPDA DTGPWCFTMD
PSIRWEYCNL TRCSDTEGTV VAPPTVIQVP SLGPPSEQDC MFGNGKGYRG KKATTVTGTP
CQEWAAQEPH RHSTFIPGTN KWAGLEKNYC RNPDGDINGP WCYTMNPRKL FDYCDIPLCA
SSSFDCGKPQ VEPKKCPGSI VGGCVAHPHS WPWQVSLRTR FGKHFCGGTL ISPEWVLTAA
HCLKKSSRPS SYKVILGAHQ EVNLESHVQE IEVSRLFLEP TQADIALLKL SRPAVITDKV
MPACLPSPDY MVTARTECYI TGWGETQGTF GTGLLKEAQL LVIENEVCNH YKYICAEHLA
RGTDSCQGDS GGPLVCFEKD KYILQGVTSW GLGCARPNKP GVYARVSRFV TWIEGMMRNN
