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Protein

Pappalysin-1

Gene

Pappa

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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. Isoform 2 cleaves IGFBP-4 very slowly compared to PAPP-A, but its ability to cleave IGFBP-5 is unaffected.1 Publication

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi559Zinc; catalyticPROSITE-ProRule annotation1
Active sitei560PROSITE-ProRule annotation1
Metal bindingi563Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi569Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:97479. Pappa.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000002924723 – 80By similarityAdd BLAST58
ChainiPRO_000002924881 – 1624Pappalysin-1Add BLAST1544

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi141 ↔ 232PROSITE-ProRule annotation
Disulfide bondi324 ↔ 619PROSITE-ProRule annotation
Disulfide bondi329 ↔ 654PROSITE-ProRule annotation
Glycosylationi387N-linked (GlcNAc...)Sequence analysis1
Glycosylationi398N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi411 ↔ 425PROSITE-ProRule annotation
Disulfide bondi421 ↔ 437PROSITE-ProRule annotation
Glycosylationi426N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi454 ↔ 470PROSITE-ProRule annotation
Disulfide bondi458Interchain (with C-49 in PRG2 proform)PROSITE-ProRule annotation
Disulfide bondi471 ↔ 482PROSITE-ProRule annotation
Glycosylationi516N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi580 ↔ 597Or C-580 with C-609PROSITE-ProRule annotation
Disulfide bondi584 ↔ 609Or C-584 with C-597PROSITE-ProRule annotation
Glycosylationi598N-linked (GlcNAc...)Sequence analysis1
Glycosylationi616N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi707 ↔ 875PROSITE-ProRule annotation
Disulfide bondi710 ↔ 878PROSITE-ProRule annotation
Glycosylationi722N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi729Interchain (with C-170 in PRG2 proform)PROSITE-ProRule annotation
Disulfide bondi750 ↔ 832PROSITE-ProRule annotation
Disulfide bondi772 ↔ 778PROSITE-ProRule annotation
Glycosylationi822N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi944 ↔ 972PROSITE-ProRule annotation
Disulfide bondi957 ↔ 968PROSITE-ProRule annotation
Disulfide bondi980 ↔ 987PROSITE-ProRule annotation
Disulfide bondi996 ↔ 1008PROSITE-ProRule annotation
Glycosylationi1023N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1033 ↔ 1067PROSITE-ProRule annotation
Disulfide bondi1048 ↔ 1136PROSITE-ProRule annotation
Disulfide bondi1189 ↔ 1202PROSITE-ProRule annotation
Disulfide bondi1207InterchainPROSITE-ProRule annotation
Disulfide bondi1212 ↔ 1266PROSITE-ProRule annotation
Glycosylationi1219N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1223N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1224 ↔ 1235PROSITE-ProRule annotation
Disulfide bondi1239 ↔ 1277PROSITE-ProRule annotation
Disulfide bondi1282 ↔ 1326PROSITE-ProRule annotation
Disulfide bondi1297 ↔ 1307PROSITE-ProRule annotation
Disulfide bondi1311 ↔ 1339PROSITE-ProRule annotation
Glycosylationi1320N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1343 ↔ 1396PROSITE-ProRule annotation
Disulfide bondi1359 ↔ 1370PROSITE-ProRule annotation
Disulfide bondi1374 ↔ 1407PROSITE-ProRule annotation
Disulfide bondi1412 ↔ 1455PROSITE-ProRule annotation
Disulfide bondi1425 ↔ 1435PROSITE-ProRule annotation
Disulfide bondi1439 ↔ 1468PROSITE-ProRule annotation
Disulfide bondi1475 ↔ 1536PROSITE-ProRule annotation
Disulfide bondi1489 ↔ 1499PROSITE-ProRule annotation
Disulfide bondi1503 ↔ 1551PROSITE-ProRule annotation
Glycosylationi1516N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1555 ↔ 1573PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ8R4K8.
PeptideAtlasiQ8R4K8.
PRIDEiQ8R4K8.

PTM databases

iPTMnetiQ8R4K8.
PhosphoSitePlusiQ8R4K8.

Expressioni

Tissue specificityi

Detected in kidney, spleen, brain, ovary, breast, skin, prostate, uterus, and placenta.2 Publications

Gene expression databases

BgeeiENSMUSG00000028370.
CleanExiMM_PAPPA.
GenevisibleiQ8R4K8. MM.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. In pregnancy serum, predominantly found as a disulfide-linked 2:2 heterotetramer with the proform of PRG2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000081545.

Structurei

3D structure databases

ProteinModelPortaliQ8R4K8.
SMRiQ8R4K8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1210 – 1279Sushi 1PROSITE-ProRule annotationAdd BLAST70
Domaini1280 – 1341Sushi 2PROSITE-ProRule annotationAdd BLAST62
Domaini1342 – 1409Sushi 3PROSITE-ProRule annotationAdd BLAST68
Domaini1410 – 1470Sushi 4PROSITE-ProRule annotationAdd BLAST61
Domaini1473 – 1553Sushi 5PROSITE-ProRule annotationAdd BLAST81

Region

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

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi24 – 82Arg-richAdd BLAST59

Sequence similaritiesi

Belongs to the peptidase M43B family.Curated
Contains 5 Sushi (CCP/SCR) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Sushi

Phylogenomic databases

eggNOGiENOG410KDUG. Eukaryota.
ENOG410YRGU. LUCA.
GeneTreeiENSGT00390000009007.
HOVERGENiHBG053501.
InParanoidiQ8R4K8.
KOiK07762.
OMAiGIQIYTL.
OrthoDBiEOG091G026Y.
PhylomeDBiQ8R4K8.
TreeFamiTF331636.

Family and domain databases

CDDicd00033. CCP. 4 hits.
cd04275. ZnMc_pappalysin_like. 1 hit.
Gene3Di2.60.120.200. 1 hit.
2.60.40.10. 2 hits.
3.40.390.10. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR013783. Ig-like_fold.
IPR006558. LamG-like.
IPR024079. MetalloPept_cat_dom.
IPR011936. Myxo_disulph_rpt.
IPR000800. Notch_dom.
IPR030433. PAPPA.
IPR008754. Peptidase_M43.
IPR000436. Sushi_SCR_CCP_dom.
[Graphical view]
PANTHERiPTHR19325:SF347. PTHR19325:SF347. 3 hits.
PfamiPF05572. Peptidase_M43. 1 hit.
PF00084. Sushi. 3 hits.
[Graphical view]
SMARTiSM00032. CCP. 4 hits.
SM00560. LamGL. 1 hit.
SM00004. NL. 3 hits.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 1 hit.
SSF57535. SSF57535. 4 hits.
TIGRFAMsiTIGR02232. myxo_disulf_rpt. 1 hit.
PROSITEiPS50923. SUSHI. 5 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

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: Q8R4K8-1) [UniParc]FASTAAdd to basket

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
MRLWSWVLRL GLLSAALGCG LAERPRRVRR DPRAVRPPRP AAGPATCATR
60 70 80 90 100
AARGRRASPP PPPGGAWEAV RVPRRRQQRA ARGAEEPSPP SRALYFSGRG
110 120 130 140 150
EQLRLRADLE LPRDAFTLQV WLRAEGGQKS PAVITGLYDK CSYTSRDRGW
160 170 180 190 200
VMGIHTTSDQ GNRDPRYFFS LKTDRARKVT TIDAHRSYLP GQWVHLAATY
210 220 230 240 250
DGRLMKLYMN GAQVATSAEQ VGGIFSPLTQ KCKVLMLGGS ALNHNFRGHI
260 270 280 290 300
EHFSLWKVAR TQREIVSDME TRGLHTPLPQ LLLQENWDNV KRTWSPMKDG
310 320 330 340 350
NSPQVEFSNA HGFLLDTNLE PPLCGQTLCD NTEVISSYNQ LPSFRQPKVV
360 370 380 390 400
RYRVVNIYDD HHENPTVSWQ QIDFQHQQLA EAFQHYNISW ELEVLNINSS
410 420 430 440 450
SLRHRLILAN CDISKIGDEK CDPECNHTLT GHDGGDCRQL RYPAFMKKQQ
460 470 480 490 500
NGVCDMDCNY ERFNFDGGEC CDPDITDVTK TCFDPDSPHR AYLDVNELKN
510 520 530 540 550
ILRLDGSTHL NIFFANSSEE ELAGVATWPW DKEALMHLGG IVLNPSFYGI
560 570 580 590 600
PGHTHTMIHE IGHSLGLYHI FRGISEIQSC SDPCMETEPS FETGDLCNDT
610 620 630 640 650
NPAPKHKFCG DPGPGNDTCG FHGFFNTPYN NFMSYADDDC TDSFTPNQVS
660 670 680 690 700
RMHCYLDLVY QSWQPSRKPA PVALAPQVVG HTMDSVMLEW FPPIDGHFFE
710 720 730 740 750
RELGSACDLC LEGRILVQYA FNASSPMPCG PSGHWSPREA EGHPDVEQPC
760 770 780 790 800
KSSVRTWSPN SAVNPHTVPP ACPEPQGCYL ELEFRYPLVP ESLTIWVTFV
810 820 830 840 850
SSDWDSSGAV NDIKLLTISG KNISLGPQNV FCDIPLTIRL RDVGEEVYGI
860 870 880 890 900
QIYTLDEHLE IDAAMLTSTV DSPLCLQCKP LQYKVLRDPP LLEDVASLLH
910 920 930 940 950
LNRRFMDTDL KLGSVYQYRI ITISGNEESE PSPAAIYTHG SGYCGDGVIQ
960 970 980 990 1000
KDQGEECDDM NKVNGDGCSL FCKQEVSFNC IDEPSRCYFH DGDGMCEEFE
1010 1020 1030 1040 1050
QKTSIKDCGV YTPQGFLDQW ASNASVSHQD QQCPGWVVIG QPAASQVCRT
1060 1070 1080 1090 1100
KVIDLSEGIS QHAWYPCTIT YPYYHLPQTT FWLQTYFSQP MVAAAVIIHL
1110 1120 1130 1140 1150
VTDGTYYGDQ KQETISVQLL DTKDQSHDLG LHVLSCRNNP LIIPVVHDLS
1160 1170 1180 1190 1200
QPFYHSQAVH VSFSSPLVAI SGVALRSFDN FDPVTLSSCQ RGETYSPAEQ
1210 1220 1230 1240 1250
SCVHFACQAA DCPELAVGNA SLNCSSNHHY HGAQCTVSCQ TGYVLQIQRD
1260 1270 1280 1290 1300
DELIKSQVGP SITVTCTEGK WNKQVACEPV DCGIPDHHHV YAASFSCPEG
1310 1320 1330 1340 1350
TTFGRRCSFQ CRHPAQLKGN NSFLTCMEDG LWSFPEALCE LMCLAPPPVP
1360 1370 1380 1390 1400
NADLQTARCR ENKHKVGSFC KYKCKPGYHV PGSSRKSKKR AFKTQCTQDG
1410 1420 1430 1440 1450
SWQEGTCVPV TCDPPPPKFH GLYQCTNGFQ FNSECRIKCE DSDASQGRGS
1460 1470 1480 1490 1500
NIIHCRKDGT WSGSFHVCRE MQGQCSAPNQ LNSNLKLQCP DGYAIGSECA
1510 1520 1530 1540 1550
ISCLDHNSES IILPVNLTVR DIPHWMNPTR VQRIVCTAGL QWYPHPALIH
1560 1570 1580 1590 1600
CVKGCEPFMG DNYCDAINNR AFCNYDGGDC CTSTVKTKKV TPFPMSCDLQ
1610 1620
NDCACRDPEA QEHNRKDLRG YSHG
Length:1,624
Mass (Da):181,318
Last modified:December 7, 2004 - v2
Checksum:iB09404C206CB60D1
GO
Isoform 2 (identifier: Q8R4K8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     490-490: R → RQSIRKRAHVVEESWLPHGKQKAKKRKRTR

Show »
Length:1,653
Mass (Da):184,839
Checksum:iEF7A13AFE698A430
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_012193490R → RQSIRKRAHVVEESWLPHGK QKAKKRKRTR in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL691491, AL691454 Genomic DNA. Translation: CAD83034.2.
AL691454, AL691491 Genomic DNA. Translation: CAD62274.2.
AF439513 mRNA. Translation: AAM12687.1.
AF439514 mRNA. Translation: AAM12688.1.
AF510317 Genomic DNA. Translation: AAM44048.1.
AF258461 mRNA. Translation: AAG09799.1.
AF260433 mRNA. Translation: AAF70319.1.
CCDSiCCDS18267.1. [Q8R4K8-1]
RefSeqiNP_067337.1. NM_021362.1. [Q8R4K8-1]
UniGeneiMm.317854.

Genome annotation databases

EnsembliENSMUST00000084501; ENSMUSP00000081545; ENSMUSG00000028370. [Q8R4K8-1]
GeneIDi18491.
KEGGimmu:18491.
UCSCiuc008thm.1. mouse. [Q8R4K8-1]
uc012dgb.1. mouse. [Q8R4K8-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL691491, AL691454 Genomic DNA. Translation: CAD83034.2.
AL691454, AL691491 Genomic DNA. Translation: CAD62274.2.
AF439513 mRNA. Translation: AAM12687.1.
AF439514 mRNA. Translation: AAM12688.1.
AF510317 Genomic DNA. Translation: AAM44048.1.
AF258461 mRNA. Translation: AAG09799.1.
AF260433 mRNA. Translation: AAF70319.1.
CCDSiCCDS18267.1. [Q8R4K8-1]
RefSeqiNP_067337.1. NM_021362.1. [Q8R4K8-1]
UniGeneiMm.317854.

3D structure databases

ProteinModelPortaliQ8R4K8.
SMRiQ8R4K8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000081545.

Protein family/group databases

MEROPSiM43.004.

PTM databases

iPTMnetiQ8R4K8.
PhosphoSitePlusiQ8R4K8.

Proteomic databases

PaxDbiQ8R4K8.
PeptideAtlasiQ8R4K8.
PRIDEiQ8R4K8.

Protocols and materials databases

DNASUi18491.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000084501; ENSMUSP00000081545; ENSMUSG00000028370. [Q8R4K8-1]
GeneIDi18491.
KEGGimmu:18491.
UCSCiuc008thm.1. mouse. [Q8R4K8-1]
uc012dgb.1. mouse. [Q8R4K8-2]

Organism-specific databases

CTDi5069.
MGIiMGI:97479. Pappa.

Phylogenomic databases

eggNOGiENOG410KDUG. Eukaryota.
ENOG410YRGU. LUCA.
GeneTreeiENSGT00390000009007.
HOVERGENiHBG053501.
InParanoidiQ8R4K8.
KOiK07762.
OMAiGIQIYTL.
OrthoDBiEOG091G026Y.
PhylomeDBiQ8R4K8.
TreeFamiTF331636.

Enzyme and pathway databases

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

Miscellaneous databases

PROiQ8R4K8.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028370.
CleanExiMM_PAPPA.
GenevisibleiQ8R4K8. MM.

Family and domain databases

CDDicd00033. CCP. 4 hits.
cd04275. ZnMc_pappalysin_like. 1 hit.
Gene3Di2.60.120.200. 1 hit.
2.60.40.10. 2 hits.
3.40.390.10. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR013783. Ig-like_fold.
IPR006558. LamG-like.
IPR024079. MetalloPept_cat_dom.
IPR011936. Myxo_disulph_rpt.
IPR000800. Notch_dom.
IPR030433. PAPPA.
IPR008754. Peptidase_M43.
IPR000436. Sushi_SCR_CCP_dom.
[Graphical view]
PANTHERiPTHR19325:SF347. PTHR19325:SF347. 3 hits.
PfamiPF05572. Peptidase_M43. 1 hit.
PF00084. Sushi. 3 hits.
[Graphical view]
SMARTiSM00032. CCP. 4 hits.
SM00560. LamGL. 1 hit.
SM00004. NL. 3 hits.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 1 hit.
SSF57535. SSF57535. 4 hits.
TIGRFAMsiTIGR02232. myxo_disulf_rpt. 1 hit.
PROSITEiPS50923. SUSHI. 5 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPAPP1_MOUSE
AccessioniPrimary (citable) accession number: Q8R4K8
Secondary accession number(s): Q80VW3
, Q80YY1, Q8K423, Q8R4K7, Q9ES06, Q9JK57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: November 30, 2016
This is version 118 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.