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};
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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 Genevisible; Q9BXP8; HS.
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.
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
//
