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Protein

Pappalysin-1

Gene

Pappa

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:97479 Pappa

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

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...) asparagineSequence analysis1
Glycosylationi398N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi411 ↔ 425PROSITE-ProRule annotation
Disulfide bondi421 ↔ 437PROSITE-ProRule annotation
Glycosylationi426N-linked (GlcNAc...) asparagineSequence 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...) asparagineSequence analysis1
Disulfide bondi580 ↔ 597Or C-580 with C-609PROSITE-ProRule annotation
Disulfide bondi584 ↔ 609Or C-584 with C-597PROSITE-ProRule annotation
Glycosylationi598N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi616N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi707 ↔ 875PROSITE-ProRule annotation
Disulfide bondi710 ↔ 878PROSITE-ProRule annotation
Glycosylationi722N-linked (GlcNAc...) asparagineSequence 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...) asparagineSequence analysis1
Disulfide bondi944 ↔ 972PROSITE-ProRule annotation
Disulfide bondi957 ↔ 968PROSITE-ProRule annotation
Disulfide bondi980 ↔ 987PROSITE-ProRule annotation
Disulfide bondi996 ↔ 1008PROSITE-ProRule annotation
Glycosylationi1023N-linked (GlcNAc...) asparagineSequence 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...) asparagineSequence analysis1
Glycosylationi1223N-linked (GlcNAc...) asparagineSequence 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...) asparagineSequence 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...) asparagineSequence 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

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
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

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

Similar proteinsi

Entry informationi

Entry nameiPAPP1_MOUSE
AccessioniPrimary (citable) accession number: Q8R4K8
Secondary accession number(s): Q80VW3
, Q80YY1, Q8K423, Q8R4K7, Q9ES06, Q9JK57
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: May 23, 2018
This is version 127 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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