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UniProtKB - Q9BXP8 (PAPP2_HUMAN)

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Protein

Pappalysin-2

Gene

PAPPA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi733Zinc; catalyticPROSITE-ProRule annotation1
Active sitei7341
Metal bindingi737Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi743Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • metalloendopeptidase activity Source: Reactome
  • metallopeptidase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

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
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)

Protein family/group databases

MEROPSiM43.005

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000116183.10
HGNCiHGNC:14615 PAPPA2
neXtProtiNX_Q9BXP8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi734E → Q: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi60676
OpenTargetsiENSG00000116183
PharmGKBiPA33373

Polymorphism and mutation databases

BioMutaiPAPPA2
DMDMi126302580

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000002924923 – 234Add BLAST212
ChainiPRO_0000029250235 – 1791Pappalysin-2Add BLAST1557

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi311N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi312 ↔ 403PROSITE-ProRule annotation
Disulfide bondi499 ↔ 793PROSITE-ProRule annotation
Disulfide bondi504 ↔ 828PROSITE-ProRule annotation
Glycosylationi562N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi574N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi586 ↔ 600PROSITE-ProRule annotation
Disulfide bondi596 ↔ 612PROSITE-ProRule annotation
Disulfide bondi628 ↔ 644PROSITE-ProRule annotation
Disulfide bondi645 ↔ 656PROSITE-ProRule annotation
Glycosylationi679N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi754 ↔ 771Or C-754 with C-783PROSITE-ProRule annotation
Disulfide bondi758 ↔ 783Or C-788 with C-771PROSITE-ProRule annotation
Glycosylationi813N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi857N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi881 ↔ 1045PROSITE-ProRule annotation
Disulfide bondi884 ↔ 1048PROSITE-ProRule annotation
Disulfide bondi924 ↔ 1003PROSITE-ProRule annotation
Glycosylationi941N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi946 ↔ 951PROSITE-ProRule annotation
Disulfide bondi1115 ↔ 1143PROSITE-ProRule annotation
Disulfide bondi1128 ↔ 1139PROSITE-ProRule annotation
Disulfide bondi1151 ↔ 1158PROSITE-ProRule annotation
Disulfide bondi1167 ↔ 1179PROSITE-ProRule annotation
Disulfide bondi1205 ↔ 1238PROSITE-ProRule annotation
Disulfide bondi1219 ↔ 1318PROSITE-ProRule annotation
Glycosylationi1243N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1308N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1326N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1344N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1371 ↔ 1385PROSITE-ProRule annotation
Disulfide bondi1396 ↔ 1448PROSITE-ProRule annotation
Glycosylationi1408N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1423 ↔ 1459PROSITE-ProRule annotation
Glycosylationi1456N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1464 ↔ 1508PROSITE-ProRule annotation
Glycosylationi1476N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1479 ↔ 1489PROSITE-ProRule annotation
Disulfide bondi1493 ↔ 1521PROSITE-ProRule annotation
Disulfide bondi1525 ↔ 1579PROSITE-ProRule annotation
Disulfide bondi1541 ↔ 1552PROSITE-ProRule annotation
Disulfide bondi1556 ↔ 1590PROSITE-ProRule annotation
Disulfide bondi1595 ↔ 1633PROSITE-ProRule annotation
Disulfide bondi1608 ↔ 1618PROSITE-ProRule annotation
Disulfide bondi1622 ↔ 1646PROSITE-ProRule annotation
Disulfide bondi1653 ↔ 1714PROSITE-ProRule annotation
Disulfide bondi1667 ↔ 1677PROSITE-ProRule annotation
Disulfide bondi1681 ↔ 1729PROSITE-ProRule annotation
Glycosylationi1694N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1733 ↔ 1751PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

MaxQBiQ9BXP8
PaxDbiQ9BXP8
PeptideAtlasiQ9BXP8
PRIDEiQ9BXP8

PTM databases

iPTMnetiQ9BXP8
PhosphoSitePlusiQ9BXP8

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

BgeeiENSG00000116183
CleanExiHS_PAPPA2
GenevisibleiQ9BXP8 HS

Organism-specific databases

HPAiHPA018412
HPA018430

Interactioni

Subunit structurei

Monomer.

Protein-protein interaction databases

BioGridi121951, 3 interactors
IntActiQ9BXP8, 3 interactors
MINTiQ9BXP8
STRINGi9606.ENSP00000356634

Structurei

3D structure databases

ProteinModelPortaliQ9BXP8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1393 – 1461Sushi 1PROSITE-ProRule annotationAdd BLAST69
Domaini1462 – 1521Sushi 2PROSITE-ProRule annotationAdd BLAST60
Domaini1523 – 1592Sushi 3PROSITE-ProRule annotationAdd BLAST70
Domaini1593 – 1648Sushi 4PROSITE-ProRule annotationAdd BLAST56
Domaini1651 – 1731Sushi 5PROSITE-ProRule annotationAdd BLAST81

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni442 – 754MetalloproteaseAdd BLAST313

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi171 – 174Poly-Thr4
Compositional biasi1654 – 1657Poly-Pro4

Sequence similaritiesi

Belongs to the peptidase M43B family.Curated

Keywords - Domaini

Repeat, Signal, Sushi

Phylogenomic databases

eggNOGiENOG410IF4C Eukaryota
ENOG410Y5CU LUCA
GeneTreeiENSGT00390000009007
HOGENOMiHOG000033711
HOVERGENiHBG053501
InParanoidiQ9BXP8
KOiK08647
OMAiECTCRDP
OrthoDBiEOG091G026Y
PhylomeDBiQ9BXP8
TreeFamiTF331636

Family and domain databases

CDDicd00033 CCP, 2 hits
cd04275 ZnMc_pappalysin_like, 1 hit
InterProiView 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
PANTHERiPTHR19325:SF1 PTHR19325:SF1, 1 hit
PfamiView protein in Pfam
PF00066 Notch, 1 hit
PF05572 Peptidase_M43, 1 hit
PF00084 Sushi, 2 hits
SMARTiView protein in SMART
SM00032 CCP, 4 hits
SM00560 LamGL, 1 hit
SM00004 NL, 2 hits
SUPFAMiSSF49265 SSF49265, 2 hits
SSF49899 SSF49899, 1 hit
SSF57535 SSF57535, 3 hits
TIGRFAMsiTIGR02232 myxo_disulf_rpt, 1 hit
PROSITEiView protein in PROSITE
PS50923 SUSHI, 3 hits
PS00142 ZINC_PROTEASE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative 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.

« Hide

        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
Length:1,791
Mass (Da):198,539
Last modified:February 20, 2007 - v4
Checksum:iF436030821EC6EDD
GO
Isoform 2 (identifier: Q9BXP8-2) [UniParc]FASTAAdd to basket
Also known as: Papp-e(2)

The sequence of this isoform differs from the canonical sequence as follows:
     811-827: DDNCTDNFTPNQVARMH → GITTVLFCFLLRIHGGL
     828-1791: Missing.

Show »
Length:827
Mass (Da):92,136
Checksum:iFB3B6F1E944F7C24
GO

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 keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti447G → E in AAL17779 (PubMed:11597188).Curated1
Sequence conflicti447G → E in CAC11134 (PubMed:11018262).Curated1
Sequence conflicti568S → N in AAL17780 (PubMed:11597188).Curated1
Sequence conflicti846I → T in AAL17779 (PubMed:11597188).Curated1
Sequence conflicti846I → T in CAC11134 (PubMed:11018262).Curated1
Sequence conflicti1343L → P in AAL17779 (PubMed:11597188).Curated1
Sequence conflicti1343L → P in CAC11134 (PubMed:11018262).Curated1
Sequence conflicti1739D → N in CAC11134 (PubMed:11018262).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051595171T → S. Corresponds to variant dbSNP:rs36112782Ensembl.1
Natural variantiVAR_0515961657P → R. Corresponds to variant dbSNP:rs34602579Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012194811 – 827DDNCT…VARMH → GITTVLFCFLLRIHGGL in isoform 2. 2 PublicationsAdd BLAST17
Alternative sequenceiVSP_012195828 – 1791Missing in isoform 2. 2 PublicationsAdd BLAST964

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.
CCDSiCCDS41438.1 [Q9BXP8-1]
CCDS41439.1 [Q9BXP8-2]
RefSeqiNP_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]
UniGeneiHs.187284

Genome annotation databases

EnsembliENST00000367661; ENSP00000356633; ENSG00000116183 [Q9BXP8-2]
ENST00000367662; ENSP00000356634; ENSG00000116183 [Q9BXP8-1]
GeneIDi60676
KEGGihsa:60676
UCSCiuc001gky.2 human [Q9BXP8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPAPP2_HUMAN
AccessioniPrimary (citable) accession number: Q9BXP8
Secondary accession number(s): A9Z1Y8
, Q96PH7, Q96PH8, Q9H4C9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: February 20, 2007
Last modified: May 23, 2018
This is version 151 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

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