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 09-DEC-2015, entry version 172. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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- RT associated plasma protein-A. Evidence for expression in the brain and RT induction by 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., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA 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., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA 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., RA Rogers J., 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 77-1627, PROTEIN SEQUENCE OF 81-98; RP 117-126; 210-224; 466-485; 507-519; 576-593; 609-621; 718-736; RP 742-754; 1006-1017; 1259-1273; 1369-1374; 1389-1398; 1490-1509; RP 1524-1533 AND 1537-1544, 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 RT derived 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; RP 576-593; 718-736; 742-754; 1259-1273; 1369-1374; 1490-1509; 1524-1533 RP AND 1537-1544, SUBUNIT, AND INTERCHAIN DISULFIDE BOND. RC TISSUE=Serum; RX PubMed=7685339; 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, RP AND DISULFIDE BONDS. RX PubMed=12421832; DOI=10.1074/jbc.M208777200; RA Overgaard M.T., Sorensen E.S., Stachowiak D., Boldt H.B., RA Kristensen L., 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 RP 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., RA Gleich G.J., 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 ENZYME 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., RA Oxvig C.; RT "Expression of recombinant human pregnancy-associated plasma protein-A RT and identification of the proform of eosinophil major basic protein as RT its 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 RT colocalization of pregnancy-associated plasma protein-A messenger RT ribonucleic acid and eosinophil granule major basic protein messenger RT ribonucleic acid in 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., RA Conover C.A., Gleich G.J., Sottrup-Jensen L., Haaning J.; RT "Messenger ribonucleic acid levels of pregnancy-associated plasma RT protein-A and the proform of eosinophil major basic protein: RT expression in human 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., RA Stigbrand T., Gleich G.J., Sottrup-Jensen L.; RT "Identification of angiotensinogen and complement C3dg as novel RT proteins binding the proform of eosinophil major basic protein in RT human pregnancy 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 RT growth factor binding protein (IGFBP)-5 independent of IGF: RT implications for the 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 RT TRIM32, 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: Cleavage of the 135-Met-|-Lys-136 bond in CC insulin-like growth factor binding protein (IGFBP)-4, and the 143- CC Ser-|-Lys-144 bond in IGFBP-5. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250}; CC -!- ENZYME REGULATION: Inhibited by complexation with the proform of CC PRG2. {ECO:0000269|PubMed:10913121}. CC -!- SUBUNIT: Homodimer; disulfide-linked. In pregnancy serum, CC predominantly found as a disulfide-linked 2:2 heterotetramer with CC the proform of PRG2. {ECO:0000269|PubMed:10913121, CC ECO:0000269|PubMed:12421832, ECO:0000269|PubMed:7685339}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10077652}. CC -!- TISSUE SPECIFICITY: High levels in placenta and pregnancy serum. CC In placenta, expressed in X cells in septa and anchoring villi, CC and in syncytiotrophoblasts in the chorionic villi. Lower levels CC are found in a variety of other tissues including kidney, CC myometrium, endometrium, ovaries, breast, prostate, bone marrow, CC colon, fibroblasts and osteoblasts. {ECO:0000269|PubMed:10077652, CC ECO:0000269|PubMed:10491647, ECO:0000269|PubMed:7508748, CC ECO:0000269|PubMed:7526035}. CC -!- DEVELOPMENTAL STAGE: Present in serum and placenta during CC pregnancy; levels increase throughout pregnancy. CC {ECO:0000269|PubMed:10491647, 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 -!- SIMILARITY: Contains 5 Sushi (CCP/SCR) domains. CC {ECO:0000255|PROSITE-ProRule:PRU00302}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC50543.1; Type=Frameshift; Positions=51, 67; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U28727; AAC50543.1; ALT_FRAME; mRNA. DR EMBL; AL353141; CAI16083.1; -; Genomic_DNA. DR EMBL; AL137024; CAI16083.1; JOINED; Genomic_DNA. DR EMBL; AL691426; CAI16083.1; JOINED; Genomic_DNA. DR EMBL; AL691426; CAI16715.1; -; Genomic_DNA. DR EMBL; AL137024; CAI16715.1; JOINED; Genomic_DNA. DR EMBL; AL353141; CAI16715.1; JOINED; 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_002581.3. DR UniGene; Hs.643599; -. DR ProteinModelPortal; Q13219; -. DR SMR; Q13219; 543-660, 1287-1506. DR BioGrid; 111104; 10. DR IntAct; Q13219; 7. DR MINT; MINT-1193478; -. DR STRING; 9606.ENSP00000330658; -. DR MEROPS; M43.004; -. DR PhosphoSite; Q13219; -. DR BioMuta; PAPPA; -. DR DMDM; 223590248; -. DR PaxDb; Q13219; -. DR PRIDE; Q13219; -. DR Ensembl; ENST00000328252; ENSP00000330658; ENSG00000182752. DR GeneID; 5069; -. DR KEGG; hsa:5069; -. DR UCSC; uc004bjn.3; human. DR CTD; 5069; -. DR GeneCards; PAPPA; -. DR H-InvDB; HIX0025885; -. DR HGNC; HGNC:8602; PAPPA. DR HPA; CAB016724; -. DR HPA; HPA001667; -. DR MIM; 176385; gene. DR neXtProt; NX_Q13219; -. DR PharmGKB; PA32935; -. DR eggNOG; ENOG410KDUG; Eukaryota. DR eggNOG; ENOG410YRGU; LUCA. DR GeneTree; ENSGT00390000009007; -. DR HOGENOM; HOG000067833; -. DR HOVERGEN; HBG053501; -. DR InParanoid; Q13219; -. DR KO; K07762; -. DR OMA; GIQIYTL; -. DR OrthoDB; EOG7HB58B; -. DR PhylomeDB; Q13219; -. DR TreeFam; TF331636; -. DR BioCyc; MetaCyc:ENSG00000119398-MONOMER; -. DR BRENDA; 3.4.24.79; 2681. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR ChiTaRS; PAPPA; human. DR GeneWiki; Pregnancy-associated_plasma_protein_A; -. DR GenomeRNAi; 5069; -. DR NextBio; 19534; -. DR PMAP-CutDB; Q13219; -. DR PRO; PR:Q13219; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; Q13219; -. DR CleanEx; HS_PAPPA; -. DR Genevisible; Q13219; HS. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro. DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0007565; P:female pregnancy; NAS:UniProtKB. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 3.40.390.10; -; 3. DR InterPro; IPR013320; ConA-like_dom. DR InterPro; IPR006558; LamG-like. DR InterPro; IPR024079; MetalloPept_cat_dom. DR InterPro; IPR011936; Myxo_disulph_rpt. DR InterPro; IPR000800; Notch_dom. DR InterPro; IPR030433; PAPPA. DR InterPro; IPR008754; Peptidase_M43. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR PANTHER; PTHR19325:SF347; PTHR19325:SF347; 3. 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 Complete proteome; Direct protein sequencing; Disulfide bond; KW Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Polymorphism; KW Protease; Reference proteome; Repeat; Secreted; Signal; Sushi; Zinc; KW Zymogen. FT SIGNAL 1 22 {ECO:0000255}. FT PROPEP 23 80 {ECO:0000269|PubMed:7508748, FT ECO:0000269|PubMed:7685339}. FT /FTId=PRO_0000029245. FT CHAIN 81 1627 Pappalysin-1. FT /FTId=PRO_0000029246. FT DOMAIN 1213 1282 Sushi 1. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 1283 1344 Sushi 2. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 1345 1412 Sushi 3. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 1413 1473 Sushi 4. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 1476 1556 Sushi 5. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT REGION 272 583 Metalloprotease. FT COMPBIAS 24 84 Arg-rich. FT ACT_SITE 563 563 {ECO:0000255|PROSITE-ProRule:PRU10095}. FT METAL 562 562 Zinc; catalytic. {ECO:0000255|PROSITE- FT ProRule:PRU10095}. FT METAL 566 566 Zinc; catalytic. {ECO:0000255|PROSITE- FT ProRule:PRU10095}. FT METAL 572 572 Zinc; catalytic. {ECO:0000255|PROSITE- FT ProRule:PRU10095}. FT CARBOHYD 390 390 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 402 402 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 429 429 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 480 480 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 601 601 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 619 619 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 725 725 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 825 825 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1026 1026 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 1222 1222 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1226 1226 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 1323 1323 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT CARBOHYD 1465 1465 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1519 1519 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:12421832}. FT DISULFID 144 235 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 327 622 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 332 657 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 414 428 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 424 440 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 457 473 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 461 461 Interchain (with C-51 in PRG2 proform). FT {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 474 485 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 583 600 Or C-583 with C-612. FT {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 587 612 Or C-587 with C-600. FT {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 710 878 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 713 881 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 732 732 Interchain (with C-169 in PRG2 proform). FT {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 753 835 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 775 781 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 947 975 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 960 971 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 983 990 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 999 1011 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1036 1070 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1051 1139 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1192 1205 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1210 1210 Interchain. {ECO:0000255|PROSITE- FT ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1215 1269 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1227 1238 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1242 1280 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1285 1329 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1300 1310 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1314 1342 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1346 1399 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1362 1373 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1377 1410 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1415 1458 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1428 1438 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1442 1471 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1478 1539 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1492 1502 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1506 1554 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT DISULFID 1558 1576 {ECO:0000255|PROSITE-ProRule:PRU00302, FT ECO:0000269|PubMed:12421832}. FT VARIANT 5 5 S -> I (in dbSNP:rs417012). FT /FTId=VAR_057091. FT VARIANT 325 325 P -> L (in dbSNP:rs445159). FT /FTId=VAR_057092. FT VARIANT 944 944 S -> R (in dbSNP:rs117124330). FT {ECO:0000269|PubMed:7508748, FT ECO:0000269|PubMed:8620868}. FT /FTId=VAR_011419. FT VARIANT 1224 1224 S -> Y (in dbSNP:rs7020782). FT {ECO:0000269|PubMed:11822024, FT ECO:0000269|PubMed:15489334}. FT /FTId=VAR_018726. FT CONFLICT 107 107 R -> RV (in Ref. 1; AAC50543 and 4; FT CAA48341). {ECO:0000305}. FT CONFLICT 511 512 TH -> RD (in Ref. 4; AA sequence). FT {ECO:0000305}. FT CONFLICT 1622 1622 R -> Q (in Ref. 3; AAH78657). FT {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 //