PAPP1_HUMAN
ID PAPP1_HUMAN Reviewed; 1627 AA.
AC Q13219; B1AMF9; Q08371; Q68G52; Q9UDK7;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 3.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Pappalysin-1;
DE EC=3.4.24.79;
DE AltName: Full=Insulin-like growth factor-dependent IGF-binding protein 4 protease;
DE Short=IGF-dependent IGFBP-4 protease;
DE Short=IGFBP-4ase;
DE AltName: Full=Pregnancy-associated plasma protein A;
DE Short=PAPP-A;
DE Flags: Precursor;
GN Name=PAPPA;
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], INDUCTION, AND VARIANT ARG-944.
RC TISSUE=Placenta;
RX PubMed=8620868; DOI=10.1111/j.1432-1033.1996.0159n.x;
RA Haaning J., Oxvig C., Overgaard M.T., Ebbesen P., Kristensen T.,
RA Sottrup-Jensen L.;
RT "Complete cDNA sequence of the preproform of human pregnancy-associated
RT plasma protein-A. Evidence for expression in the brain and induction by
RT cAMP.";
RL Eur. J. Biochem. 237:159-163(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TYR-1224.
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 77-1627, PROTEIN SEQUENCE OF 82-98; 117-126;
RP 210-224; 466-485; 507-519; 576-593; 609-621; 718-736; 742-754; 1006-1017;
RP 1259-1273; 1369-1374; 1389-1398; 1490-1509; 1524-1533 AND 1537-1544,
RP VARIANT ARG-944, AND TISSUE SPECIFICITY.
RC TISSUE=Placenta, and Serum;
RX PubMed=7508748; DOI=10.1021/bi00172a040;
RA Kristensen T., Oxvig C., Sand O., Moller N.P.H., Sottrup-Jensen L.;
RT "Amino acid sequence of human pregnancy-associated plasma protein-A derived
RT from cloned cDNA.";
RL Biochemistry 33:1592-1598(1994).
RN [5]
RP PROTEIN SEQUENCE OF 81-89; 117-126; 210-224; 460-485; 507-519; 576-593;
RP 718-736; 742-754; 1259-1273; 1369-1374; 1490-1509; 1524-1533 AND 1537-1544,
RP SUBUNIT, AND INTERCHAIN DISULFIDE BOND.
RC TISSUE=Serum;
RX PubMed=7685339; DOI=10.1016/s0021-9258(18)31378-4;
RA Oxvig C., Sand O., Kristensen T., Gleich G.J., Sottrup-Jensen L.;
RT "Circulating human pregnancy-associated plasma protein-A is disulfide-
RT bridged to the proform of eosinophil major basic protein.";
RL J. Biol. Chem. 268:12243-12246(1993).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-402; ASN-429; ASN-480;
RP ASN-601; ASN-619; ASN-725; ASN-1026; ASN-1226; ASN-1323 AND ASN-1519, AND
RP DISULFIDE BONDS.
RX PubMed=12421832; DOI=10.1074/jbc.m208777200;
RA Overgaard M.T., Sorensen E.S., Stachowiak D., Boldt H.B., Kristensen L.,
RA Sottrup-Jensen L., Oxvig C.;
RT "Complex of pregnancy-associated plasma protein-A and the proform of
RT eosinophil major basic protein. Disulfide structure and carbohydrate
RT attachment sites.";
RL J. Biol. Chem. 278:2106-2117(2003).
RN [7]
RP IDENTIFICATION, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Fibroblast;
RX PubMed=10077652; DOI=10.1073/pnas.96.6.3149;
RA Lawrence J.B., Oxvig C., Overgaard M.T., Sottrup-Jensen L., Gleich G.J.,
RA Hays L.G., Yates J.R. III, Conover C.A.;
RT "The insulin-like growth factor (IGF)-dependent IGF binding protein-4
RT protease secreted by human fibroblasts is pregnancy-associated plasma
RT protein-A.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3149-3153(1999).
RN [8]
RP FUNCTION, SUBUNIT, AND ACTIVITY REGULATION.
RX PubMed=10913121; DOI=10.1074/jbc.m001384200;
RA Overgaard M.T., Haaning J., Boldt H.B., Olsen I.M., Laursen L.S.,
RA Christiansen M., Gleich G.J., Sottrup-Jensen L., Conover C.A., Oxvig C.;
RT "Expression of recombinant human pregnancy-associated plasma protein-A and
RT identification of the proform of eosinophil major basic protein as its
RT physiological inhibitor.";
RL J. Biol. Chem. 275:31128-31133(2000).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=7526035;
RA Bonno M., Oxvig C., Kephart G.M., Wagner J.M., Kristensen T.,
RA Sottrup-Jensen L., Gleich G.J.;
RT "Localization of pregnancy-associated plasma protein-A and colocalization
RT of pregnancy-associated plasma protein-A messenger ribonucleic acid and
RT eosinophil granule major basic protein messenger ribonucleic acid in
RT placenta.";
RL Lab. Invest. 71:560-566(1994).
RN [10]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10491647; DOI=10.1095/biolreprod61.4.1083;
RA Overgaard M.T., Oxvig C., Christiansen M., Lawrence J.B., Conover C.A.,
RA Gleich G.J., Sottrup-Jensen L., Haaning J.;
RT "Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A
RT and the proform of eosinophil major basic protein: expression in human
RT reproductive and nonreproductive tissues.";
RL Biol. Reprod. 61:1083-1089(1999).
RN [11]
RP DEVELOPMENTAL STAGE.
RX PubMed=7539791; DOI=10.1074/jbc.270.23.13645;
RA Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I., Stigbrand T.,
RA Gleich G.J., Sottrup-Jensen L.;
RT "Identification of angiotensinogen and complement C3dg as novel proteins
RT binding the proform of eosinophil major basic protein in human pregnancy
RT serum and plasma.";
RL J. Biol. Chem. 270:13645-13651(1995).
RN [12]
RP FUNCTION.
RX PubMed=11522292; DOI=10.1016/s0014-5793(01)02760-0;
RA Laursen L.S., Overgaard M.T., Soe R., Boldt H.B., Sottrup-Jensen L.,
RA Giudice L.C., Conover C.A., Oxvig C.;
RT "Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth
RT factor binding protein (IGFBP)-5 independent of IGF: implications for the
RT mechanism of IGFBP-4 proteolysis by PAPP-A.";
RL FEBS Lett. 504:36-40(2001).
RN [13]
RP VARIANT TYR-1224.
RX PubMed=11822024; DOI=10.1086/339083;
RA Frosk P., Weiler T., Nylen E., Sudha T., Greenberg C.R., Morgan K.,
RA Fujiwara T.M., Wrogemann K.;
RT "Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32,
RT a putative E3-ubiquitin-ligase gene.";
RL Am. J. Hum. Genet. 70:663-672(2002).
CC -!- FUNCTION: Metalloproteinase which specifically cleaves IGFBP-4 and
CC IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is
CC dramatically enhanced by the presence of IGF, whereas cleavage of
CC IGFBP-5 is slightly inhibited by the presence of IGF.
CC {ECO:0000269|PubMed:10077652, ECO:0000269|PubMed:10913121,
CC ECO:0000269|PubMed:11522292}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of the 135-Met-|-Lys-136 bond in insulin-like growth
CC factor binding protein (IGFBP)-4, and the 143-Ser-|-Lys-144 bond in
CC IGFBP-5.; EC=3.4.24.79;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by complexation with the proform of
CC PRG2. {ECO:0000269|PubMed:10913121}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. In pregnancy serum, predominantly
CC found as a disulfide-linked 2:2 heterotetramer with the proform of
CC PRG2. {ECO:0000269|PubMed:10913121, ECO:0000269|PubMed:12421832,
CC ECO:0000269|PubMed:7685339}.
CC -!- INTERACTION:
CC Q13219; P13727: PRG2; NbExp=2; IntAct=EBI-1221991, EBI-716689;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10077652}.
CC -!- TISSUE SPECIFICITY: High levels in placenta and pregnancy serum. In
CC placenta, expressed in X cells in septa and anchoring villi, and in
CC syncytiotrophoblasts in the chorionic villi. Lower levels are found in
CC a variety of other tissues including kidney, myometrium, endometrium,
CC ovaries, breast, prostate, bone marrow, colon, fibroblasts and
CC osteoblasts. {ECO:0000269|PubMed:10077652, ECO:0000269|PubMed:10491647,
CC ECO:0000269|PubMed:7508748, ECO:0000269|PubMed:7526035}.
CC -!- DEVELOPMENTAL STAGE: Present in serum and placenta during pregnancy;
CC levels increase throughout pregnancy. {ECO:0000269|PubMed:10491647,
CC ECO:0000269|PubMed:7539791}.
CC -!- INDUCTION: By 8-bromoadenosine-3',5'-phosphate.
CC {ECO:0000269|PubMed:8620868}.
CC -!- PTM: There appear to be no free sulfhydryl groups.
CC -!- SIMILARITY: Belongs to the peptidase M43B family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50543.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U28727; AAC50543.1; ALT_FRAME; mRNA.
DR EMBL; AL137024; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353141; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL691426; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC078657; AAH78657.1; -; mRNA.
DR EMBL; X68280; CAA48341.1; -; mRNA.
DR CCDS; CCDS6813.1; -.
DR PIR; S65464; S65464.
DR RefSeq; NP_002572.2; NM_002581.4.
DR AlphaFoldDB; Q13219; -.
DR BioGRID; 111104; 14.
DR CORUM; Q13219; -.
DR IntAct; Q13219; 10.
DR MINT; Q13219; -.
DR STRING; 9606.ENSP00000330658; -.
DR DrugBank; DB12695; Phenethyl Isothiocyanate.
DR MEROPS; M43.004; -.
DR GlyConnect; 1594; 1 N-Linked glycan (1 site).
DR GlyGen; Q13219; 14 sites, 1 N-linked glycan (1 site).
DR iPTMnet; Q13219; -.
DR PhosphoSitePlus; Q13219; -.
DR BioMuta; PAPPA; -.
DR DMDM; 223590248; -.
DR EPD; Q13219; -.
DR jPOST; Q13219; -.
DR MassIVE; Q13219; -.
DR PaxDb; Q13219; -.
DR PeptideAtlas; Q13219; -.
DR PRIDE; Q13219; -.
DR ProteomicsDB; 59231; -.
DR Antibodypedia; 3385; 876 antibodies from 32 providers.
DR DNASU; 5069; -.
DR Ensembl; ENST00000328252.4; ENSP00000330658.3; ENSG00000182752.10.
DR GeneID; 5069; -.
DR KEGG; hsa:5069; -.
DR MANE-Select; ENST00000328252.4; ENSP00000330658.3; NM_002581.5; NP_002572.2.
DR UCSC; uc004bjn.4; human.
DR CTD; 5069; -.
DR DisGeNET; 5069; -.
DR GeneCards; PAPPA; -.
DR HGNC; HGNC:8602; PAPPA.
DR HPA; ENSG00000182752; Tissue enriched (placenta).
DR MIM; 176385; gene.
DR neXtProt; NX_Q13219; -.
DR OpenTargets; ENSG00000182752; -.
DR PharmGKB; PA32935; -.
DR VEuPathDB; HostDB:ENSG00000182752; -.
DR eggNOG; ENOG502QQ7Z; Eukaryota.
DR GeneTree; ENSGT00940000156654; -.
DR HOGENOM; CLU_002636_2_0_1; -.
DR InParanoid; Q13219; -.
DR OMA; FIDQTQC; -.
DR OrthoDB; 105200at2759; -.
DR PhylomeDB; Q13219; -.
DR TreeFam; TF331636; -.
DR BioCyc; MetaCyc:ENSG00000119398-MON; -.
DR BRENDA; 3.4.24.79; 2681.
DR PathwayCommons; Q13219; -.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR SignaLink; Q13219; -.
DR BioGRID-ORCS; 5069; 28 hits in 1069 CRISPR screens.
DR ChiTaRS; PAPPA; human.
DR GeneWiki; Pregnancy-associated_plasma_protein_A; -.
DR GenomeRNAi; 5069; -.
DR Pharos; Q13219; Tbio.
DR PRO; PR:Q13219; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q13219; protein.
DR Bgee; ENSG00000182752; Expressed in decidua and 175 other tissues.
DR Genevisible; Q13219; HS.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004222; F:metalloendopeptidase activity; EXP:Reactome.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007565; P:female pregnancy; TAS:ProtInc.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl.
DR GO; GO:0032354; P:response to follicle-stimulating hormone; IEA:Ensembl.
DR CDD; cd00033; CCP; 4.
DR CDD; cd04275; ZnMc_pappalysin_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR006558; LamG-like.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR011936; Myxo_disulph_rpt.
DR InterPro; IPR000800; Notch_dom.
DR InterPro; IPR030433; PAPPA.
DR InterPro; IPR043543; PAPPA/PAPPA2.
DR InterPro; IPR008754; Peptidase_M43.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR PANTHER; PTHR46130; PTHR46130; 1.
DR PANTHER; PTHR46130:SF2; PTHR46130:SF2; 1.
DR Pfam; PF05572; Peptidase_M43; 1.
DR Pfam; PF00084; Sushi; 3.
DR SMART; SM00032; CCP; 4.
DR SMART; SM00560; LamGL; 1.
DR SMART; SM00004; NL; 3.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF57535; SSF57535; 4.
DR TIGRFAMs; TIGR02232; myxo_disulf_rpt; 1.
DR PROSITE; PS50923; SUSHI; 5.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Sushi; Zinc; Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..81
FT /evidence="ECO:0000269|PubMed:7508748,
FT ECO:0000269|PubMed:7685339"
FT /id="PRO_0000029245"
FT CHAIN 82..1627
FT /note="Pappalysin-1"
FT /id="PRO_0000029246"
FT DOMAIN 1213..1282
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 1283..1344
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 1345..1412
FT /note="Sushi 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 1413..1473
FT /note="Sushi 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 1476..1556
FT /note="Sushi 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT REGION 23..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 272..583
FT /note="Metalloprotease"
FT REGION 733..754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 563
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 562
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 566
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 572
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 480
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 601
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 619
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 725
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 825
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1026
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 1222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1226
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 1323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT CARBOHYD 1465
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1519
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12421832"
FT DISULFID 144..235
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 327..622
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 332..657
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 414..428
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 424..440
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 457..473
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 461
FT /note="Interchain (with C-51 in PRG2 proform)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 474..485
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 583..600
FT /note="Or C-583 with C-612"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 587..612
FT /note="Or C-587 with C-600"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 710..878
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 713..881
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 732
FT /note="Interchain (with C-169 in PRG2 proform)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 753..835
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 775..781
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 947..975
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 960..971
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 983..990
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 999..1011
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1036..1070
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1051..1139
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1192..1205
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1210
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1215..1269
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1227..1238
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1242..1280
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1285..1329
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1300..1310
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1314..1342
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1346..1399
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1362..1373
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1377..1410
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1415..1458
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1428..1438
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1442..1471
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1478..1539
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1492..1502
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1506..1554
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT DISULFID 1558..1576
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302,
FT ECO:0000269|PubMed:12421832"
FT VARIANT 5
FT /note="S -> I (in dbSNP:rs417012)"
FT /id="VAR_057091"
FT VARIANT 325
FT /note="P -> L (in dbSNP:rs445159)"
FT /id="VAR_057092"
FT VARIANT 944
FT /note="S -> R (in dbSNP:rs117124330)"
FT /evidence="ECO:0000269|PubMed:7508748,
FT ECO:0000269|PubMed:8620868"
FT /id="VAR_011419"
FT VARIANT 1224
FT /note="S -> Y (in dbSNP:rs7020782)"
FT /evidence="ECO:0000269|PubMed:11822024,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_018726"
FT CONFLICT 107
FT /note="R -> RV (in Ref. 1; AAC50543 and 4; CAA48341)"
FT /evidence="ECO:0000305"
FT CONFLICT 511..512
FT /note="TH -> RD (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1622
FT /note="R -> Q (in Ref. 3; AAH78657)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1627 AA; 180973 MW; 202ECA62C1107207 CRC64;
MRLWSWVLHL GLLSAALGCG LAERPRRARR DPRAGRPPRP AAGPATCATR AARGRRASPP
PPPPPGGAWE AVRVPRRRQQ REARGATEEP SPPSRALYFS GRGEQLRLRA DLELPRDAFT
LQVWLRAEGG QRSPAVITGL YDKCSYISRD RGWVVGIHTI SDQDNKDPRY FFSLKTDRAR
QVTTINAHRS YLPGQWVYLA ATYDGQFMKL YVNGAQVATS GEQVGGIFSP LTQKCKVLML
GGSALNHNYR GYIEHFSLWK VARTQREILS DMETHGAHTA LPQLLLQENW DNVKHAWSPM
KDGSSPKVEF SNAHGFLLDT SLEPPLCGQT LCDNTEVIAS YNQLSSFRQP KVVRYRVVNL
YEDDHKNPTV TREQVDFQHH QLAEAFKQYN ISWELDVLEV SNSSLRRRLI LANCDISKIG
DENCDPECNH TLTGHDGGDC RHLRHPAFVK KQHNGVCDMD CNYERFNFDG GECCDPEITN
VTQTCFDPDS PHRAYLDVNE LKNILKLDGS THLNIFFAKS SEEELAGVAT WPWDKEALMH
LGGIVLNPSF YGMPGHTHTM IHEIGHSLGL YHVFRGISEI QSCSDPCMET EPSFETGDLC
NDTNPAPKHK SCGDPGPGND TCGFHSFFNT PYNNFMSYAD DDCTDSFTPN QVARMHCYLD
LVYQGWQPSR KPAPVALAPQ VLGHTTDSVT LEWFPPIDGH FFERELGSAC HLCLEGRILV
QYASNASSPM PCSPSGHWSP REAEGHPDVE QPCKSSVRTW SPNSAVNPHT VPPACPEPQG
CYLELEFLYP LVPESLTIWV TFVSTDWDSS GAVNDIKLLA VSGKNISLGP QNVFCDVPLT
IRLWDVGEEV YGIQIYTLDE HLEIDAAMLT STADTPLCLQ CKPLKYKVVR DPPLQMDVAS
ILHLNRKFVD MDLNLGSVYQ YWVITISGTE ESEPSPAVTY IHGSGYCGDG IIQKDQGEQC
DDMNKINGDG CSLFCRQEVS FNCIDEPSRC YFHDGDGVCE EFEQKTSIKD CGVYTPQGFL
DQWASNASVS HQDQQCPGWV IIGQPAASQV CRTKVIDLSE GISQHAWYPC TISYPYSQLA
QTTFWLRAYF SQPMVAAAVI VHLVTDGTYY GDQKQETISV QLLDTKDQSH DLGLHVLSCR
NNPLIIPVVH DLSQPFYHSQ AVRVSFSSPL VAISGVALRS FDNFDPVTLS SCQRGETYSP
AEQSCVHFAC EKTDCPELAV ENASLNCSSS DRYHGAQCTV SCRTGYVLQI RRDDELIKSQ
TGPSVTVTCT EGKWNKQVAC EPVDCSIPDH HQVYAASFSC PEGTTFGSQC SFQCRHPAQL
KGNNSLLTCM EDGLWSFPEA LCELMCLAPP PVPNADLQTA RCRENKHKVG SFCKYKCKPG
YHVPGSSRKS KKRAFKTQCT QDGSWQEGAC VPVTCDPPPP KFHGLYQCTN GFQFNSECRI
KCEDSDASQG LGSNVIHCRK DGTWNGSFHV CQEMQGQCSV PNELNSNLKL QCPDGYAIGS
ECATSCLDHN SESIILPMNV TVRDIPHWLN PTRVERVVCT AGLKWYPHPA LIHCVKGCEP
FMGDNYCDAI NNRAFCNYDG GDCCTSTVKT KKVTPFPMSC DLQGDCACRD PQAQEHSRKD
LRGYSHG
