UniProtKB - Q9BXP8 (PAPP2_HUMAN)
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Protein
Pappalysin-2
Gene
PAPPA2
Organism
Homo sapiens (Human)
Status
Functioni
Metalloproteinase which specifically cleaves insulin-like growth factor binding protein (IGFBP)-5 at the '163-Ser-|-Lys-164' bond. Shows limited proteolysis toward IGFBP-3.1 Publication
Cofactori
Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 733 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Active sitei | 734 | 1 | ||
Metal bindingi | 737 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 743 | Zinc; catalyticPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- metalloendopeptidase activity Source: Reactome
- metallopeptidase activity Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- bone morphogenesis Source: Ensembl
- cellular protein metabolic process Source: Reactome
- proteolysis Source: UniProtKB
- regulation of cell growth Source: UniProtKB
- response to salt stress Source: Ensembl
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-HSA-381426. Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). |
Protein family/group databases
MEROPSi | M43.005. |
Names & Taxonomyi
Protein namesi | Recommended name: Pappalysin-2 (EC:3.4.24.-)Alternative name(s): Pregnancy-associated plasma protein A2 Short name: PAPP-A2 Pregnancy-associated plasma protein E1 Short name: PAPP-E |
Gene namesi | Name:PAPPA2 Synonyms:PLAC3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000116183.10. |
HGNCi | HGNC:14615. PAPPA2. |
neXtProti | NX_Q9BXP8. |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 734 | E → Q: Loss of activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 60676. |
OpenTargetsi | ENSG00000116183. |
PharmGKBi | PA33373. |
Polymorphism and mutation databases
BioMutai | PAPPA2. |
DMDMi | 126302580. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 22 | Sequence analysisAdd BLAST | 22 | |
PropeptideiPRO_0000029249 | 23 – 234 | Add BLAST | 212 | |
ChainiPRO_0000029250 | 235 – 1791 | Pappalysin-2Add BLAST | 1557 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 311 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 312 ↔ 403 | PROSITE-ProRule annotation | ||
Disulfide bondi | 499 ↔ 793 | PROSITE-ProRule annotation | ||
Disulfide bondi | 504 ↔ 828 | PROSITE-ProRule annotation | ||
Glycosylationi | 562 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 574 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 586 ↔ 600 | PROSITE-ProRule annotation | ||
Disulfide bondi | 596 ↔ 612 | PROSITE-ProRule annotation | ||
Disulfide bondi | 628 ↔ 644 | PROSITE-ProRule annotation | ||
Disulfide bondi | 645 ↔ 656 | PROSITE-ProRule annotation | ||
Glycosylationi | 679 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 754 ↔ 771 | Or C-754 with C-783PROSITE-ProRule annotation | ||
Disulfide bondi | 758 ↔ 783 | Or C-788 with C-771PROSITE-ProRule annotation | ||
Glycosylationi | 813 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 857 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 881 ↔ 1045 | PROSITE-ProRule annotation | ||
Disulfide bondi | 884 ↔ 1048 | PROSITE-ProRule annotation | ||
Disulfide bondi | 924 ↔ 1003 | PROSITE-ProRule annotation | ||
Glycosylationi | 941 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 946 ↔ 951 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1115 ↔ 1143 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1128 ↔ 1139 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1151 ↔ 1158 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1167 ↔ 1179 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1205 ↔ 1238 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1219 ↔ 1318 | PROSITE-ProRule annotation | ||
Glycosylationi | 1243 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1308 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1326 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 1344 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1371 ↔ 1385 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1396 ↔ 1448 | PROSITE-ProRule annotation | ||
Glycosylationi | 1408 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1423 ↔ 1459 | PROSITE-ProRule annotation | ||
Glycosylationi | 1456 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1464 ↔ 1508 | PROSITE-ProRule annotation | ||
Glycosylationi | 1476 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1479 ↔ 1489 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1493 ↔ 1521 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1525 ↔ 1579 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1541 ↔ 1552 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1556 ↔ 1590 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1595 ↔ 1633 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1608 ↔ 1618 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1622 ↔ 1646 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1653 ↔ 1714 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1667 ↔ 1677 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1681 ↔ 1729 | PROSITE-ProRule annotation | ||
Glycosylationi | 1694 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 1733 ↔ 1751 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bond, Glycoprotein, ZymogenProteomic databases
MaxQBi | Q9BXP8. |
PaxDbi | Q9BXP8. |
PeptideAtlasi | Q9BXP8. |
PRIDEi | Q9BXP8. |
PTM databases
iPTMneti | Q9BXP8. |
PhosphoSitePlusi | Q9BXP8. |
Expressioni
Tissue specificityi
Expressed abundantly in placenta, and non-pregnant mammary gland with low expression in the kidney, fetal brain and pancreas.2 Publications
Gene expression databases
Bgeei | ENSG00000116183. |
CleanExi | HS_PAPPA2. |
Genevisiblei | Q9BXP8. HS. |
Organism-specific databases
HPAi | HPA018412. HPA018430. |
Interactioni
Subunit structurei
Monomer.
Protein-protein interaction databases
BioGridi | 121951. 3 interactors. |
IntActi | Q9BXP8. 3 interactors. |
MINTi | Q9BXP8. |
STRINGi | 9606.ENSP00000356634. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1393 – 1461 | Sushi 1PROSITE-ProRule annotationAdd BLAST | 69 | |
Domaini | 1462 – 1521 | Sushi 2PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 1523 – 1592 | Sushi 3PROSITE-ProRule annotationAdd BLAST | 70 | |
Domaini | 1593 – 1648 | Sushi 4PROSITE-ProRule annotationAdd BLAST | 56 | |
Domaini | 1651 – 1731 | Sushi 5PROSITE-ProRule annotationAdd BLAST | 81 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 442 – 754 | MetalloproteaseAdd BLAST | 313 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 171 – 174 | Poly-Thr | 4 | |
Compositional biasi | 1654 – 1657 | Poly-Pro | 4 |
Sequence similaritiesi
Belongs to the peptidase M43B family.Curated
Keywords - Domaini
Repeat, Signal, SushiPhylogenomic databases
eggNOGi | ENOG410IF4C. Eukaryota. ENOG410Y5CU. LUCA. |
GeneTreei | ENSGT00390000009007. |
HOGENOMi | HOG000033711. |
HOVERGENi | HBG053501. |
InParanoidi | Q9BXP8. |
KOi | K08647. |
OMAi | ECTCRDP. |
OrthoDBi | EOG091G026Y. |
PhylomeDBi | Q9BXP8. |
TreeFami | TF331636. |
Family and domain databases
CDDi | cd00033. CCP. 2 hits. cd04275. ZnMc_pappalysin_like. 1 hit. |
InterProi | View protein in InterPro IPR013320. ConA-like_dom_sf. IPR036116. FN3_sf. IPR006558. LamG-like. IPR011936. Myxo_disulph_rpt. IPR000800. Notch_dom. IPR026918. PAPPA2. IPR008754. Peptidase_M43. IPR035976. Sushi/SCR/CCP_sf. IPR000436. Sushi_SCR_CCP_dom. |
PANTHERi | PTHR19325:SF1. PTHR19325:SF1. 1 hit. |
Pfami | View protein in Pfam PF00066. Notch. 1 hit. PF05572. Peptidase_M43. 1 hit. PF00084. Sushi. 2 hits. |
SMARTi | View protein in SMART SM00032. CCP. 4 hits. SM00560. LamGL. 1 hit. SM00004. NL. 2 hits. |
SUPFAMi | SSF49265. SSF49265. 2 hits. SSF49899. SSF49899. 1 hit. SSF57535. SSF57535. 3 hits. |
TIGRFAMsi | TIGR02232. myxo_disulf_rpt. 1 hit. |
PROSITEi | View protein in PROSITE PS50923. SUSHI. 3 hits. PS00142. ZINC_PROTEASE. 1 hit. |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9BXP8-1) [UniParc]FASTAAdd to basket
Also known as: Papp-e(1)
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MMCLKILRIS LAILAGWALC SANSELGWTR KKSLVEREHL NQVLLEGERC
60 70 80 90 100
WLGAKVRRPR ASPQHHLFGV YPSRAGNYLR PYPVGEQEIH HTGRSKPDTE
110 120 130 140 150
GNAVSLVPPD LTENPAGLRG AVEEPAAPWV GDSPIGQSEL LGDDDAYLGN
160 170 180 190 200
QRSKESLGEA GIQKGSAMAA TTTTAIFTTL NEPKPETQRR GWAKSRQRRQ
210 220 230 240 250
VWKRRAEDGQ GDSGISSHFQ PWPKHSLKHR VKKSPPEESN QNGGEGSYRE
260 270 280 290 300
AETFNSQVGL PILYFSGRRE RLLLRPEVLA EIPREAFTVE AWVKPEGGQN
310 320 330 340 350
NPAIIAGVFD NCSHTVSDKG WALGIRSGKD KGKRDARFFF SLCTDRVKKA
360 370 380 390 400
TILISHSRYQ PGTWTHVAAT YDGRHMALYV DGTQVASSLD QSGPLNSPFM
410 420 430 440 450
ASCRSLLLGG DSSEDGHYFR GHLGTLVFWS TALPQSHFQH SSQHSSGEEE
460 470 480 490 500
ATDLVLTASF EPVNTEWVPF RDEKYPRLEV LQGFEPEPEI LSPLQPPLCG
510 520 530 540 550
QTVCDNVELI SQYNGYWPLR GEKVIRYQVV NICDDEGLNP IVSEEQIRLQ
560 570 580 590 600
HEALNEAFSR YNISWQLSVH QVHNSTLRHR VVLVNCEPSK IGNDHCDPEC
610 620 630 640 650
EHPLTGYDGG DCRLQGRCYS WNRRDGLCHV ECNNMLNDFD DGDCCDPQVA
660 670 680 690 700
DVRKTCFDPD SPKRAYMSVK ELKEALQLNS THFLNIYFAS SVREDLAGAA
710 720 730 740 750
TWPWDKDAVT HLGGIVLSPA YYGMPGHTDT MIHEVGHVLG LYHVFKGVSE
760 770 780 790 800
RESCNDPCKE TVPSMETGDL CADTAPTPKS ELCREPEPTS DTCGFTRFPG
810 820 830 840 850
APFTNYMSYT DDNCTDNFTP NQVARMHCYL DLVYQQWTES RKPTPIPIPP
860 870 880 890 900
MVIGQTNKSL TIHWLPPISG VVYDRASGSL CGACTEDGTF RQYVHTASSR
910 920 930 940 950
RVCDSSGYWT PEEAVGPPDV DQPCEPSLQA WSPEVHLYHM NMTVPCPTEG
960 970 980 990 1000
CSLELLFQHP VQADTLTLWV TSFFMESSQV LFDTEILLEN KESVHLGPLD
1010 1020 1030 1040 1050
TFCDIPLTIK LHVDGKVSGV KVYTFDERIE IDAALLTSQP HSPLCSGCRP
1060 1070 1080 1090 1100
VRYQVLRDPP FASGLPVVVT HSHRKFTDVE VTPGQMYQYQ VLAEAGGELG
1110 1120 1130 1140 1150
EASPPLNHIH GAPYCGDGKV SERLGEECDD GDLVSGDGCS KVCELEEGFN
1160 1170 1180 1190 1200
CVGEPSLCYM YEGDGICEPF ERKTSIVDCG IYTPKGYLDQ WATRAYSSHE
1210 1220 1230 1240 1250
DKKKCPVSLV TGEPHSLICT SYHPDLPNHR PLTGWFPCVA SENETQDDRS
1260 1270 1280 1290 1300
EQPEGSLKKE DEVWLKVCFN RPGEARAIFI FLTTDGLVPG EHQQPTVTLY
1310 1320 1330 1340 1350
LTDVRGSNHS LGTYGLSCQH NPLIINVTHH QNVLFHHTTS VLLNFSSPRV
1360 1370 1380 1390 1400
GISAVALRTS SRIGLSAPSN CISEDEGQNH QGQSCIHRPC GKQDSCPSLL
1410 1420 1430 1440 1450
LDHADVVNCT SIGPGLMKCA ITCQRGFALQ ASSGQYIRPM QKEILLTCSS
1460 1470 1480 1490 1500
GHWDQNVSCL PVDCGVPDPS LVNYANFSCS EGTKFLKRCS ISCVPPAKLQ
1510 1520 1530 1540 1550
GLSPWLTCLE DGLWSLPEVY CKLECDAPPI ILNANLLLPH CLQDNHDVGT
1560 1570 1580 1590 1600
ICKYECKPGY YVAESAEGKV RNKLLKIQCL EGGIWEQGSC IPVVCEPPPP
1610 1620 1630 1640 1650
VFEGMYECTN GFSLDSQCVL NCNQEREKLP ILCTKEGLWT QEFKLCENLQ
1660 1670 1680 1690 1700
GECPPPPSEL NSVEYKCEQG YGIGAVCSPL CVIPPSDPVM LPENITADTL
1710 1720 1730 1740 1750
EHWMEPVKVQ SIVCTGRRQW HPDPVLVHCI QSCEPFQADG WCDTINNRAY
1760 1770 1780 1790
CHYDGGDCCS STLSSKKVIP FAADCDLDEC TCRDPKAEEN Q
Sequence cautioni
The sequence AAL17779 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAL17780 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAC11134 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 447 | G → E in AAL17779 (PubMed:11597188).Curated | 1 | |
Sequence conflicti | 447 | G → E in CAC11134 (PubMed:11018262).Curated | 1 | |
Sequence conflicti | 568 | S → N in AAL17780 (PubMed:11597188).Curated | 1 | |
Sequence conflicti | 846 | I → T in AAL17779 (PubMed:11597188).Curated | 1 | |
Sequence conflicti | 846 | I → T in CAC11134 (PubMed:11018262).Curated | 1 | |
Sequence conflicti | 1343 | L → P in AAL17779 (PubMed:11597188).Curated | 1 | |
Sequence conflicti | 1343 | L → P in CAC11134 (PubMed:11018262).Curated | 1 | |
Sequence conflicti | 1739 | D → N in CAC11134 (PubMed:11018262).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051595 | 171 | T → S. Corresponds to variant dbSNP:rs36112782Ensembl. | 1 | |
Natural variantiVAR_051596 | 1657 | P → R. Corresponds to variant dbSNP:rs34602579Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_012194 | 811 – 827 | DDNCT…VARMH → GITTVLFCFLLRIHGGL in isoform 2. 2 PublicationsAdd BLAST | 17 | |
Alternative sequenceiVSP_012195 | 828 – 1791 | Missing in isoform 2. 2 PublicationsAdd BLAST | 964 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF311940 mRNA. Translation: AAK31073.1. AF342989 mRNA. Translation: AAL17779.1. Different initiation. AF342990 mRNA. Translation: AAL17780.1. Different initiation. AL031290 Genomic DNA. No translation available. AL031734 Genomic DNA. No translation available. AL139282 Genomic DNA. No translation available. AL596254 Genomic DNA. No translation available. CH471067 Genomic DNA. Translation: EAW91003.1. BC117193 mRNA. Translation: AAI17194.3. BC117195 mRNA. Translation: AAI17196.3. AJ278348 mRNA. Translation: CAC11134.1. Different initiation. |
CCDSi | CCDS41438.1. [Q9BXP8-1] CCDS41439.1. [Q9BXP8-2] |
RefSeqi | NP_064714.2. NM_020318.2. [Q9BXP8-1] NP_068755.2. NM_021936.2. [Q9BXP8-2] XP_005245479.1. XM_005245422.3. [Q9BXP8-1] XP_011508159.1. XM_011509857.1. [Q9BXP8-1] XP_011508160.1. XM_011509858.2. [Q9BXP8-1] XP_016857512.1. XM_017002023.1. [Q9BXP8-1] XP_016857513.1. XM_017002024.1. [Q9BXP8-1] XP_016857514.1. XM_017002025.1. [Q9BXP8-1] |
UniGenei | Hs.187284. |
Genome annotation databases
Ensembli | ENST00000367661; ENSP00000356633; ENSG00000116183. [Q9BXP8-2] ENST00000367662; ENSP00000356634; ENSG00000116183. [Q9BXP8-1] |
GeneIDi | 60676. |
KEGGi | hsa:60676. |
UCSCi | uc001gky.2. human. [Q9BXP8-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | PAPP2_HUMAN | |
Accessioni | Q9BXP8Primary (citable) accession number: Q9BXP8 Secondary accession number(s): A9Z1Y8 Q9H4C9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 7, 2004 |
Last sequence update: | February 20, 2007 | |
Last modified: | March 28, 2018 | |
This is version 149 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |