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Protein

Pappalysin-1

Gene

PAPPA

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

Functioni

Metalloproteinase which specifically cleaves IGFBP-4 and IGFBP-5, resulting in release of bound IGF. Cleavage of IGFBP-4 is dramatically enhanced by the presence of IGF, whereas cleavage of IGFBP-5 is slightly inhibited by the presence of IGF.3 Publications

Catalytic activityi

Cleavage of the 135-Met-|-Lys-136 bond in insulin-like growth factor binding protein (IGFBP)-4, and the 143-Ser-|-Lys-144 bond in IGFBP-5.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Inhibited by complexation with the proform of PRG2.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi562Zinc; catalyticPROSITE-ProRule annotation1
Active sitei563PROSITE-ProRule annotation1
Metal bindingi566Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi572Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • metalloendopeptidase activity Source: Reactome
  • metallopeptidase activity Source: UniProtKB
  • zinc ion binding Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000119398-MONOMER
BRENDAi3.4.24.79 2681
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

MEROPSiM43.004

Names & Taxonomyi

Protein namesi
Recommended name:
Pappalysin-1 (EC:3.4.24.79)
Alternative name(s):
Insulin-like growth factor-dependent IGF-binding protein 4 protease
Short name:
IGF-dependent IGFBP-4 protease
Short name:
IGFBP-4ase
Pregnancy-associated plasma protein A
Short name:
PAPP-A
Gene namesi
Name:PAPPA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000182752.9
HGNCiHGNC:8602 PAPPA
MIMi176385 gene
neXtProtiNX_Q13219

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

Organism-specific databases

DisGeNETi5069
OpenTargetsiENSG00000182752
PharmGKBiPA32935

Polymorphism and mutation databases

BioMutaiPAPPA
DMDMi223590248

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000002924523 – 802 PublicationsAdd BLAST58
ChainiPRO_000002924681 – 1627Pappalysin-1Add BLAST1547

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi144 ↔ 235PROSITE-ProRule annotation1 Publication
Disulfide bondi327 ↔ 622PROSITE-ProRule annotation1 Publication
Disulfide bondi332 ↔ 657PROSITE-ProRule annotation1 Publication
Glycosylationi390N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi402N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi414 ↔ 428PROSITE-ProRule annotation1 Publication
Disulfide bondi424 ↔ 440PROSITE-ProRule annotation1 Publication
Glycosylationi429N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi457 ↔ 473PROSITE-ProRule annotation1 Publication
Disulfide bondi461Interchain (with C-51 in PRG2 proform)PROSITE-ProRule annotation1 Publication
Disulfide bondi474 ↔ 485PROSITE-ProRule annotation1 Publication
Glycosylationi480N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi583 ↔ 600Or C-583 with C-612PROSITE-ProRule annotation1 Publication
Disulfide bondi587 ↔ 612Or C-587 with C-600PROSITE-ProRule annotation1 Publication
Glycosylationi601N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi619N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi710 ↔ 878PROSITE-ProRule annotation1 Publication
Disulfide bondi713 ↔ 881PROSITE-ProRule annotation1 Publication
Glycosylationi725N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi732Interchain (with C-169 in PRG2 proform)PROSITE-ProRule annotation1 Publication
Disulfide bondi753 ↔ 835PROSITE-ProRule annotation1 Publication
Disulfide bondi775 ↔ 781PROSITE-ProRule annotation1 Publication
Glycosylationi825N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi947 ↔ 975PROSITE-ProRule annotation1 Publication
Disulfide bondi960 ↔ 971PROSITE-ProRule annotation1 Publication
Disulfide bondi983 ↔ 990PROSITE-ProRule annotation1 Publication
Disulfide bondi999 ↔ 1011PROSITE-ProRule annotation1 Publication
Glycosylationi1026N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi1036 ↔ 1070PROSITE-ProRule annotation1 Publication
Disulfide bondi1051 ↔ 1139PROSITE-ProRule annotation1 Publication
Disulfide bondi1192 ↔ 1205PROSITE-ProRule annotation1 Publication
Disulfide bondi1210InterchainPROSITE-ProRule annotation1 Publication
Disulfide bondi1215 ↔ 1269PROSITE-ProRule annotation1 Publication
Glycosylationi1222N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi1226N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi1227 ↔ 1238PROSITE-ProRule annotation1 Publication
Disulfide bondi1242 ↔ 1280PROSITE-ProRule annotation1 Publication
Disulfide bondi1285 ↔ 1329PROSITE-ProRule annotation1 Publication
Disulfide bondi1300 ↔ 1310PROSITE-ProRule annotation1 Publication
Disulfide bondi1314 ↔ 1342PROSITE-ProRule annotation1 Publication
Glycosylationi1323N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi1346 ↔ 1399PROSITE-ProRule annotation1 Publication
Disulfide bondi1362 ↔ 1373PROSITE-ProRule annotation1 Publication
Disulfide bondi1377 ↔ 1410PROSITE-ProRule annotation1 Publication
Disulfide bondi1415 ↔ 1458PROSITE-ProRule annotation1 Publication
Disulfide bondi1428 ↔ 1438PROSITE-ProRule annotation1 Publication
Disulfide bondi1442 ↔ 1471PROSITE-ProRule annotation1 Publication
Glycosylationi1465N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi1478 ↔ 1539PROSITE-ProRule annotation1 Publication
Disulfide bondi1492 ↔ 1502PROSITE-ProRule annotation1 Publication
Disulfide bondi1506 ↔ 1554PROSITE-ProRule annotation1 Publication
Glycosylationi1519N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi1558 ↔ 1576PROSITE-ProRule annotation1 Publication

Post-translational modificationi

There appear to be no free sulfhydryl groups.

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ13219
PeptideAtlasiQ13219
PRIDEiQ13219

PTM databases

iPTMnetiQ13219
PhosphoSitePlusiQ13219

Miscellaneous databases

PMAP-CutDBQ13219

Expressioni

Tissue specificityi

High levels in placenta and pregnancy serum. In placenta, expressed in X cells in septa and anchoring villi, and in syncytiotrophoblasts in the chorionic villi. Lower levels are found in a variety of other tissues including kidney, myometrium, endometrium, ovaries, breast, prostate, bone marrow, colon, fibroblasts and osteoblasts.4 Publications

Developmental stagei

Present in serum and placenta during pregnancy; levels increase throughout pregnancy.2 Publications

Inductioni

By 8-bromoadenosine-3',5'-phosphate.1 Publication

Gene expression databases

BgeeiENSG00000182752
CleanExiHS_PAPPA
GenevisibleiQ13219 HS

Organism-specific databases

HPAiCAB016724
HPA001667

Interactioni

Subunit structurei

Homodimer; disulfide-linked. In pregnancy serum, predominantly found as a disulfide-linked 2:2 heterotetramer with the proform of PRG2.3 Publications

Protein-protein interaction databases

BioGridi111104, 10 interactors
CORUMiQ13219
IntActiQ13219, 7 interactors
MINTiQ13219
STRINGi9606.ENSP00000330658

Structurei

3D structure databases

ProteinModelPortaliQ13219
SMRiQ13219
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1213 – 1282Sushi 1PROSITE-ProRule annotationAdd BLAST70
Domaini1283 – 1344Sushi 2PROSITE-ProRule annotationAdd BLAST62
Domaini1345 – 1412Sushi 3PROSITE-ProRule annotationAdd BLAST68
Domaini1413 – 1473Sushi 4PROSITE-ProRule annotationAdd BLAST61
Domaini1476 – 1556Sushi 5PROSITE-ProRule annotationAdd BLAST81

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni272 – 583MetalloproteaseAdd BLAST312

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi24 – 84Arg-richAdd BLAST61

Sequence similaritiesi

Belongs to the peptidase M43B family.Curated

Keywords - Domaini

Repeat, Signal, Sushi

Phylogenomic databases

eggNOGiENOG410KDUG Eukaryota
ENOG410YRGU LUCA
GeneTreeiENSGT00390000009007
HOGENOMiHOG000067833
HOVERGENiHBG053501
InParanoidiQ13219
KOiK07762
OMAiGIQIYTL
OrthoDBiEOG091G026Y
PhylomeDBiQ13219
TreeFamiTF331636

Family and domain databases

CDDicd00033 CCP, 4 hits
cd04275 ZnMc_pappalysin_like, 1 hit
Gene3Di3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR013320 ConA-like_dom_sf
IPR006558 LamG-like
IPR024079 MetalloPept_cat_dom_sf
IPR011936 Myxo_disulph_rpt
IPR000800 Notch_dom
IPR030433 PAPPA
IPR008754 Peptidase_M43
IPR035976 Sushi/SCR/CCP_sf
IPR000436 Sushi_SCR_CCP_dom
PANTHERiPTHR19325:SF347 PTHR19325:SF347, 1 hit
PfamiView protein in Pfam
PF05572 Peptidase_M43, 1 hit
PF00084 Sushi, 3 hits
SMARTiView protein in SMART
SM00032 CCP, 4 hits
SM00560 LamGL, 1 hit
SM00004 NL, 3 hits
SUPFAMiSSF49899 SSF49899, 1 hit
SSF57535 SSF57535, 4 hits
TIGRFAMsiTIGR02232 myxo_disulf_rpt, 1 hit
PROSITEiView protein in PROSITE
PS50923 SUSHI, 5 hits
PS00142 ZINC_PROTEASE, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q13219-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLWSWVLHL GLLSAALGCG LAERPRRARR DPRAGRPPRP AAGPATCATR
60 70 80 90 100
AARGRRASPP PPPPPGGAWE AVRVPRRRQQ REARGATEEP SPPSRALYFS
110 120 130 140 150
GRGEQLRLRA DLELPRDAFT LQVWLRAEGG QRSPAVITGL YDKCSYISRD
160 170 180 190 200
RGWVVGIHTI SDQDNKDPRY FFSLKTDRAR QVTTINAHRS YLPGQWVYLA
210 220 230 240 250
ATYDGQFMKL YVNGAQVATS GEQVGGIFSP LTQKCKVLML GGSALNHNYR
260 270 280 290 300
GYIEHFSLWK VARTQREILS DMETHGAHTA LPQLLLQENW DNVKHAWSPM
310 320 330 340 350
KDGSSPKVEF SNAHGFLLDT SLEPPLCGQT LCDNTEVIAS YNQLSSFRQP
360 370 380 390 400
KVVRYRVVNL YEDDHKNPTV TREQVDFQHH QLAEAFKQYN ISWELDVLEV
410 420 430 440 450
SNSSLRRRLI LANCDISKIG DENCDPECNH TLTGHDGGDC RHLRHPAFVK
460 470 480 490 500
KQHNGVCDMD CNYERFNFDG GECCDPEITN VTQTCFDPDS PHRAYLDVNE
510 520 530 540 550
LKNILKLDGS THLNIFFAKS SEEELAGVAT WPWDKEALMH LGGIVLNPSF
560 570 580 590 600
YGMPGHTHTM IHEIGHSLGL YHVFRGISEI QSCSDPCMET EPSFETGDLC
610 620 630 640 650
NDTNPAPKHK SCGDPGPGND TCGFHSFFNT PYNNFMSYAD DDCTDSFTPN
660 670 680 690 700
QVARMHCYLD LVYQGWQPSR KPAPVALAPQ VLGHTTDSVT LEWFPPIDGH
710 720 730 740 750
FFERELGSAC HLCLEGRILV QYASNASSPM PCSPSGHWSP REAEGHPDVE
760 770 780 790 800
QPCKSSVRTW SPNSAVNPHT VPPACPEPQG CYLELEFLYP LVPESLTIWV
810 820 830 840 850
TFVSTDWDSS GAVNDIKLLA VSGKNISLGP QNVFCDVPLT IRLWDVGEEV
860 870 880 890 900
YGIQIYTLDE HLEIDAAMLT STADTPLCLQ CKPLKYKVVR DPPLQMDVAS
910 920 930 940 950
ILHLNRKFVD MDLNLGSVYQ YWVITISGTE ESEPSPAVTY IHGSGYCGDG
960 970 980 990 1000
IIQKDQGEQC DDMNKINGDG CSLFCRQEVS FNCIDEPSRC YFHDGDGVCE
1010 1020 1030 1040 1050
EFEQKTSIKD CGVYTPQGFL DQWASNASVS HQDQQCPGWV IIGQPAASQV
1060 1070 1080 1090 1100
CRTKVIDLSE GISQHAWYPC TISYPYSQLA QTTFWLRAYF SQPMVAAAVI
1110 1120 1130 1140 1150
VHLVTDGTYY GDQKQETISV QLLDTKDQSH DLGLHVLSCR NNPLIIPVVH
1160 1170 1180 1190 1200
DLSQPFYHSQ AVRVSFSSPL VAISGVALRS FDNFDPVTLS SCQRGETYSP
1210 1220 1230 1240 1250
AEQSCVHFAC EKTDCPELAV ENASLNCSSS DRYHGAQCTV SCRTGYVLQI
1260 1270 1280 1290 1300
RRDDELIKSQ TGPSVTVTCT EGKWNKQVAC EPVDCSIPDH HQVYAASFSC
1310 1320 1330 1340 1350
PEGTTFGSQC SFQCRHPAQL KGNNSLLTCM EDGLWSFPEA LCELMCLAPP
1360 1370 1380 1390 1400
PVPNADLQTA RCRENKHKVG SFCKYKCKPG YHVPGSSRKS KKRAFKTQCT
1410 1420 1430 1440 1450
QDGSWQEGAC VPVTCDPPPP KFHGLYQCTN GFQFNSECRI KCEDSDASQG
1460 1470 1480 1490 1500
LGSNVIHCRK DGTWNGSFHV CQEMQGQCSV PNELNSNLKL QCPDGYAIGS
1510 1520 1530 1540 1550
ECATSCLDHN SESIILPMNV TVRDIPHWLN PTRVERVVCT AGLKWYPHPA
1560 1570 1580 1590 1600
LIHCVKGCEP FMGDNYCDAI NNRAFCNYDG GDCCTSTVKT KKVTPFPMSC
1610 1620
DLQGDCACRD PQAQEHSRKD LRGYSHG
Length:1,627
Mass (Da):180,973
Last modified:February 10, 2009 - v3
Checksum:i202ECA62C1107207
GO

Sequence cautioni

The sequence AAC50543 differs from that shown. Reason: Frameshift at positions 51 and 67.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti107R → RV in AAC50543 (PubMed:8620868).Curated1
Sequence conflicti107R → RV in CAA48341 (PubMed:7508748).Curated1
Sequence conflicti511 – 512TH → RD AA sequence (PubMed:7508748).Curated2
Sequence conflicti1622R → Q in AAH78657 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0570915S → I. Corresponds to variant dbSNP:rs417012Ensembl.1
Natural variantiVAR_057092325P → L. Corresponds to variant dbSNP:rs445159Ensembl.1
Natural variantiVAR_011419944S → R2 PublicationsCorresponds to variant dbSNP:rs117124330Ensembl.1
Natural variantiVAR_0187261224S → Y2 PublicationsCorresponds to variant dbSNP:rs7020782Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28727 mRNA Translation: AAC50543.1 Frameshift.
AL137024 Genomic DNA No translation available.
AL353141 Genomic DNA No translation available.
AL691426 Genomic DNA No translation available.
BC078657 mRNA Translation: AAH78657.1
X68280 mRNA Translation: CAA48341.1
CCDSiCCDS6813.1
PIRiS65464
RefSeqiNP_002572.2, NM_002581.4
UniGeneiHs.643599

Genome annotation databases

EnsembliENST00000328252; ENSP00000330658; ENSG00000182752
GeneIDi5069
KEGGihsa:5069
UCSCiuc004bjn.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPAPP1_HUMAN
AccessioniPrimary (citable) accession number: Q13219
Secondary accession number(s): B1AMF9
, Q08371, Q68G52, Q9UDK7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: February 10, 2009
Last modified: May 23, 2018
This is version 191 of the entry and version 3 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

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