ID PAPP2_HUMAN Reviewed; 1791 AA. AC Q9BXP8; A9Z1Y8; Q96PH7; Q96PH8; Q9H4C9; DT 07-DEC-2004, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 4. DT 27-MAR-2024, entry version 186. DE RecName: Full=Pappalysin-2; DE EC=3.4.24.-; DE AltName: Full=Pregnancy-associated plasma protein A2; DE Short=PAPP-A2; DE AltName: Full=Pregnancy-associated plasma protein E1; DE Short=PAPP-E; DE Flags: Precursor; GN Name=PAPPA2; Synonyms=PLAC3; 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] (ISOFORM 1), PROTEIN SEQUENCE OF 234-241, TISSUE RP SPECIFICITY, MUTAGENESIS OF GLU-734, AND FUNCTION. RC TISSUE=Term placenta; RX PubMed=11264294; DOI=10.1074/jbc.m102191200; RA Overgaard M.T., Boldt H.B., Laursen L.S., Sottrup-Jensen L., Conover C.A., RA Oxvig C.; RT "Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin-like RT growth factor-binding protein-5 proteinase."; RL J. Biol. Chem. 276:21849-21853(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RX PubMed=11597188; DOI=10.1053/plac.2001.0709; RA Page N.M., Butlin D.J., Lomthaisong K., Lowry P.J.; RT "The characterization of pregnancy associated plasma protein-E and the RT identification of an alternative splice variant."; RL Placenta 22:681-687(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 20-1791 (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=11018262; DOI=10.1016/s0167-4781(00)00195-0; RA Farr M., Struebe J., Geppert H.-G., Kocourek A., Mahne M., Tschesche H.; RT "Pregnancy-associated plasma protein-E (PAPP-E)."; RL Biochim. Biophys. Acta 1493:356-362(2000). RN [7] RP INVOLVEMENT IN SSDA, VARIANT SSDA VAL-1033, AND FUNCTION. RX PubMed=26902202; DOI=10.15252/emmm.201506106; RA Dauber A., Munoz-Calvo M.T., Barrios V., Domene H.M., Kloverpris S., RA Serra-Juhe C., Desikan V., Pozo J., Muzumdar R., Martos-Moreno G.A., RA Hawkins F., Jasper H.G., Conover C.A., Frystyk J., Yakar S., Hwa V., RA Chowen J.A., Oxvig C., Rosenfeld R.G., Perez-Jurado L.A., Argente J.; RT "Mutations in pregnancy-associated plasma protein A2 cause short stature RT due to low IGF-I availability."; RL EMBO Mol. Med. 8:363-374(2016). RN [8] RP INVOLVEMENT IN SSDA, AND VARIANT SSDA 886-GLU--GLN-1791 DEL. RX PubMed=34272725; DOI=10.1111/cge.14030; RA Babiker A., Al Noaim K., Al Swaid A., Alfadhel M., Deeb A., RA Martin-Rivada A., Barrios V., Perez-Jurado L.A., Alfares A., Al Alwan I., RA Argente J.; RT "Short stature with low insulin-like growth factor 1 availability due to RT pregnancy-associated plasma protein A2 deficiency in a Saudi family."; RL Clin. Genet. 100:601-606(2021). CC -!- FUNCTION: Metalloproteinase which specifically cleaves insulin-like CC growth factor binding protein (IGFBP)-5 at the '163-Ser-|-Lys-164' CC bond. Shows limited proteolysis toward IGFBP-3. CC {ECO:0000269|PubMed:11264294, ECO:0000269|PubMed:26902202}. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250}; CC -!- SUBUNIT: Monomer. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=Papp-e(1); CC IsoId=Q9BXP8-1; Sequence=Displayed; CC Name=2; Synonyms=Papp-e(2); CC IsoId=Q9BXP8-2; Sequence=VSP_012194, VSP_012195; CC -!- TISSUE SPECIFICITY: Expressed abundantly in placenta, and non-pregnant CC mammary gland with low expression in the kidney, fetal brain and CC pancreas. {ECO:0000269|PubMed:11264294, ECO:0000269|PubMed:11597188}. CC -!- DISEASE: Short stature, Dauber-Argente type (SSDA) [MIM:619489]: An CC autosomal recessive disorder characterized by progressive postnatal CC growth failure, moderate microcephaly, thin long bones, mildly CC decreased bone density, and elevated serum levels of total IGF1, IGFBP3 CC and IGFBP5. Levels of circulating free IGF1 are reduced. CC {ECO:0000269|PubMed:26902202, ECO:0000269|PubMed:34272725}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the peptidase M43B family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAL17779.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAL17780.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAC11134.1; Type=Erroneous initiation; 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; AF311940; AAK31073.1; -; mRNA. DR EMBL; AF342989; AAL17779.1; ALT_INIT; mRNA. DR EMBL; AF342990; AAL17780.1; ALT_INIT; mRNA. DR EMBL; AL031290; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL031734; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL139282; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL596254; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91003.1; -; Genomic_DNA. DR EMBL; BC117193; AAI17194.3; -; mRNA. DR EMBL; BC117195; AAI17196.3; -; mRNA. DR EMBL; AJ278348; CAC11134.1; ALT_INIT; mRNA. DR CCDS; CCDS41438.1; -. [Q9BXP8-1] DR CCDS; CCDS41439.1; -. [Q9BXP8-2] DR RefSeq; NP_064714.2; NM_020318.2. [Q9BXP8-1] DR RefSeq; NP_068755.2; NM_021936.2. [Q9BXP8-2] DR RefSeq; XP_005245479.1; XM_005245422.3. [Q9BXP8-1] DR RefSeq; XP_011508159.1; XM_011509857.1. [Q9BXP8-1] DR RefSeq; XP_011508160.1; XM_011509858.2. DR RefSeq; XP_016857512.1; XM_017002023.1. [Q9BXP8-1] DR RefSeq; XP_016857513.1; XM_017002024.1. [Q9BXP8-1] DR RefSeq; XP_016857514.1; XM_017002025.1. DR PDB; 8SL1; EM; 3.13 A; A=235-1791. DR PDBsum; 8SL1; -. DR AlphaFoldDB; Q9BXP8; -. DR EMDB; EMD-40571; -. DR SMR; Q9BXP8; -. DR BioGRID; 121951; 4. DR IntAct; Q9BXP8; 3. DR MINT; Q9BXP8; -. DR STRING; 9606.ENSP00000356634; -. DR MEROPS; M43.005; -. DR GlyCosmos; Q9BXP8; 15 sites, No reported glycans. DR GlyGen; Q9BXP8; 15 sites. DR iPTMnet; Q9BXP8; -. DR PhosphoSitePlus; Q9BXP8; -. DR BioMuta; PAPPA2; -. DR DMDM; 126302580; -. DR jPOST; Q9BXP8; -. DR MassIVE; Q9BXP8; -. DR MaxQB; Q9BXP8; -. DR PaxDb; 9606-ENSP00000356634; -. DR PeptideAtlas; Q9BXP8; -. DR ProteomicsDB; 79480; -. [Q9BXP8-1] DR ProteomicsDB; 79481; -. [Q9BXP8-2] DR Antibodypedia; 11013; 178 antibodies from 30 providers. DR DNASU; 60676; -. DR Ensembl; ENST00000367661.7; ENSP00000356633.3; ENSG00000116183.11. [Q9BXP8-2] DR Ensembl; ENST00000367662.5; ENSP00000356634.3; ENSG00000116183.11. [Q9BXP8-1] DR GeneID; 60676; -. DR KEGG; hsa:60676; -. DR MANE-Select; ENST00000367662.5; ENSP00000356634.3; NM_020318.3; NP_064714.2. DR UCSC; uc001gky.2; human. [Q9BXP8-1] DR AGR; HGNC:14615; -. DR CTD; 60676; -. DR DisGeNET; 60676; -. DR GeneCards; PAPPA2; -. DR HGNC; HGNC:14615; PAPPA2. DR HPA; ENSG00000116183; Tissue enriched (placenta). DR MalaCards; PAPPA2; -. DR MIM; 619485; gene. DR MIM; 619489; phenotype. DR neXtProt; NX_Q9BXP8; -. DR OpenTargets; ENSG00000116183; -. DR PharmGKB; PA33373; -. DR VEuPathDB; HostDB:ENSG00000116183; -. DR eggNOG; ENOG502QQ7Z; Eukaryota. DR GeneTree; ENSGT00940000158543; -. DR HOGENOM; CLU_342536_0_0_1; -. DR InParanoid; Q9BXP8; -. DR OMA; TGHSRYQ; -. DR OrthoDB; 5483399at2759; -. DR PhylomeDB; Q9BXP8; -. DR TreeFam; TF331636; -. DR PathwayCommons; Q9BXP8; -. 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; Q9BXP8; -. DR BioGRID-ORCS; 60676; 15 hits in 1147 CRISPR screens. DR ChiTaRS; PAPPA2; human. DR GeneWiki; PAPPA2; -. DR GenomeRNAi; 60676; -. DR Pharos; Q9BXP8; Tbio. DR PRO; PR:Q9BXP8; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9BXP8; Protein. DR Bgee; ENSG00000116183; Expressed in decidua and 139 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. 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; NAS:UniProtKB. DR GO; GO:0060349; P:bone morphogenesis; IEA:Ensembl. DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central. DR GO; GO:0019538; P:protein metabolic process; TAS:Reactome. DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB. DR GO; GO:0001558; P:regulation of cell growth; NAS:UniProtKB. DR GO; GO:0009651; P:response to salt stress; IEA:Ensembl. DR CDD; cd00033; CCP; 2. DR CDD; cd04275; ZnMc_pappalysin_like; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 2. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR036116; FN3_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; IPR043543; PAPPA/PAPPA2. DR InterPro; IPR008754; Peptidase_M43. DR InterPro; IPR035976; Sushi/SCR/CCP_sf. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR NCBIfam; TIGR02232; myxo_disulf_rpt; 1. DR PANTHER; PTHR46130; LAMGL DOMAIN-CONTAINING PROTEIN; 1. DR PANTHER; PTHR46130:SF1; PAPPALYSIN-2; 1. DR Pfam; PF13385; Laminin_G_3; 1. DR Pfam; PF05572; Peptidase_M43; 1. DR Pfam; PF00084; Sushi; 2. DR SMART; SM00032; CCP; 4. DR SMART; SM00560; LamGL; 1. DR SMART; SM00004; NL; 2. DR SUPFAM; SSF57535; Complement control module/SCR domain; 3. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF49265; Fibronectin type III; 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 2. DR PROSITE; PS50923; SUSHI; 3. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; Q9BXP8; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disease variant; Disulfide bond; Dwarfism; 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..234 FT /id="PRO_0000029249" FT CHAIN 235..1791 FT /note="Pappalysin-2" FT /id="PRO_0000029250" FT DOMAIN 1393..1461 FT /note="Sushi 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 1462..1521 FT /note="Sushi 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 1523..1592 FT /note="Sushi 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 1593..1648 FT /note="Sushi 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DOMAIN 1651..1731 FT /note="Sushi 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT REGION 89..145 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 177..248 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 442..754 FT /note="Metalloprotease" FT ACT_SITE 734 FT BINDING 733 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 737 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 743 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095" FT CARBOHYD 311 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 562 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 574 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 679 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 813 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 857 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 941 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1243 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1308 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1326 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1344 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1408 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1456 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1476 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 1694 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 312..403 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 499..793 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 504..828 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 586..600 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 596..612 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 628..644 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 645..656 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 754..771 FT /note="Or C-754 with C-783" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 758..783 FT /note="Or C-788 with C-771" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 881..1045 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 884..1048 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 924..1003 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 946..951 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1115..1143 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1128..1139 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1151..1158 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1167..1179 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1205..1238 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1219..1318 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1371..1385 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1396..1448 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1423..1459 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1464..1508 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1479..1489 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1493..1521 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1525..1579 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1541..1552 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1556..1590 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1595..1633 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1608..1618 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1622..1646 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1653..1714 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1667..1677 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1681..1729 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT DISULFID 1733..1751 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302" FT VAR_SEQ 811..827 FT /note="DDNCTDNFTPNQVARMH -> GITTVLFCFLLRIHGGL (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:11597188, FT ECO:0000303|PubMed:15489334" FT /id="VSP_012194" FT VAR_SEQ 828..1791 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11597188, FT ECO:0000303|PubMed:15489334" FT /id="VSP_012195" FT VARIANT 171 FT /note="T -> S (in dbSNP:rs36112782)" FT /id="VAR_051595" FT VARIANT 886..1791 FT /note="Missing (in SSDA)" FT /evidence="ECO:0000269|PubMed:34272725" FT /id="VAR_086132" FT VARIANT 1033 FT /note="A -> V (in SSDA; loss of catalytic activity toward FT IGFBP3 and IGFBP5)" FT /evidence="ECO:0000269|PubMed:26902202" FT /id="VAR_086133" FT VARIANT 1657 FT /note="P -> R (in dbSNP:rs34602579)" FT /id="VAR_051596" FT MUTAGEN 734 FT /note="E->Q: Loss of activity." FT /evidence="ECO:0000269|PubMed:11264294" FT CONFLICT 447 FT /note="G -> E (in Ref. 2; AAL17779 and 6; CAC11134)" FT /evidence="ECO:0000305" FT CONFLICT 568 FT /note="S -> N (in Ref. 2; AAL17780)" FT /evidence="ECO:0000305" FT CONFLICT 846 FT /note="I -> T (in Ref. 2; AAL17779 and 6; CAC11134)" FT /evidence="ECO:0000305" FT CONFLICT 1343 FT /note="L -> P (in Ref. 2; AAL17779 and 6; CAC11134)" FT /evidence="ECO:0000305" FT CONFLICT 1739 FT /note="D -> N (in Ref. 6; CAC11134)" FT /evidence="ECO:0000305" SQ SEQUENCE 1791 AA; 198539 MW; F436030821EC6EDD CRC64; MMCLKILRIS LAILAGWALC SANSELGWTR KKSLVEREHL NQVLLEGERC WLGAKVRRPR ASPQHHLFGV YPSRAGNYLR PYPVGEQEIH HTGRSKPDTE GNAVSLVPPD LTENPAGLRG AVEEPAAPWV GDSPIGQSEL LGDDDAYLGN QRSKESLGEA GIQKGSAMAA TTTTAIFTTL NEPKPETQRR GWAKSRQRRQ VWKRRAEDGQ GDSGISSHFQ PWPKHSLKHR VKKSPPEESN QNGGEGSYRE AETFNSQVGL PILYFSGRRE RLLLRPEVLA EIPREAFTVE AWVKPEGGQN NPAIIAGVFD NCSHTVSDKG WALGIRSGKD KGKRDARFFF SLCTDRVKKA TILISHSRYQ PGTWTHVAAT YDGRHMALYV DGTQVASSLD QSGPLNSPFM ASCRSLLLGG DSSEDGHYFR GHLGTLVFWS TALPQSHFQH SSQHSSGEEE ATDLVLTASF EPVNTEWVPF RDEKYPRLEV LQGFEPEPEI LSPLQPPLCG QTVCDNVELI SQYNGYWPLR GEKVIRYQVV NICDDEGLNP IVSEEQIRLQ HEALNEAFSR YNISWQLSVH QVHNSTLRHR VVLVNCEPSK IGNDHCDPEC EHPLTGYDGG DCRLQGRCYS WNRRDGLCHV ECNNMLNDFD DGDCCDPQVA DVRKTCFDPD SPKRAYMSVK ELKEALQLNS THFLNIYFAS SVREDLAGAA TWPWDKDAVT HLGGIVLSPA YYGMPGHTDT MIHEVGHVLG LYHVFKGVSE RESCNDPCKE TVPSMETGDL CADTAPTPKS ELCREPEPTS DTCGFTRFPG APFTNYMSYT DDNCTDNFTP NQVARMHCYL DLVYQQWTES RKPTPIPIPP MVIGQTNKSL TIHWLPPISG VVYDRASGSL CGACTEDGTF RQYVHTASSR RVCDSSGYWT PEEAVGPPDV DQPCEPSLQA WSPEVHLYHM NMTVPCPTEG CSLELLFQHP VQADTLTLWV TSFFMESSQV LFDTEILLEN KESVHLGPLD TFCDIPLTIK LHVDGKVSGV KVYTFDERIE IDAALLTSQP HSPLCSGCRP VRYQVLRDPP FASGLPVVVT HSHRKFTDVE VTPGQMYQYQ VLAEAGGELG EASPPLNHIH GAPYCGDGKV SERLGEECDD GDLVSGDGCS KVCELEEGFN CVGEPSLCYM YEGDGICEPF ERKTSIVDCG IYTPKGYLDQ WATRAYSSHE DKKKCPVSLV TGEPHSLICT SYHPDLPNHR PLTGWFPCVA SENETQDDRS EQPEGSLKKE DEVWLKVCFN RPGEARAIFI FLTTDGLVPG EHQQPTVTLY LTDVRGSNHS LGTYGLSCQH NPLIINVTHH QNVLFHHTTS VLLNFSSPRV GISAVALRTS SRIGLSAPSN CISEDEGQNH QGQSCIHRPC GKQDSCPSLL LDHADVVNCT SIGPGLMKCA ITCQRGFALQ ASSGQYIRPM QKEILLTCSS GHWDQNVSCL PVDCGVPDPS LVNYANFSCS EGTKFLKRCS ISCVPPAKLQ GLSPWLTCLE DGLWSLPEVY CKLECDAPPI ILNANLLLPH CLQDNHDVGT ICKYECKPGY YVAESAEGKV RNKLLKIQCL EGGIWEQGSC IPVVCEPPPP VFEGMYECTN GFSLDSQCVL NCNQEREKLP ILCTKEGLWT QEFKLCENLQ GECPPPPSEL NSVEYKCEQG YGIGAVCSPL CVIPPSDPVM LPENITADTL EHWMEPVKVQ SIVCTGRRQW HPDPVLVHCI QSCEPFQADG WCDTINNRAY CHYDGGDCCS STLSSKKVIP FAADCDLDEC TCRDPKAEEN Q //