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Q8R4K8 (PAPP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Pappa
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1624 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.2

Catalytic activity

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.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

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

Subcellular location

Secreted.

Tissue specificity

Detected in kidney, spleen, brain, ovary, breast, skin, prostate, uterus, and placenta. Ref.2 Ref.4

Sequence similarities

Belongs to the peptidase M43B family.

Contains 5 Sushi (CCP/SCR) domains.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8R4K8-1)

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.
Isoform 2 (identifier: Q8R4K8-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Propeptide23 – 8058 By similarity
PRO_0000029247
Chain81 – 16241544Pappalysin-1
PRO_0000029248

Regions

Domain1210 – 127970Sushi 1
Domain1280 – 134162Sushi 2
Domain1342 – 140968Sushi 3
Domain1410 – 147061Sushi 4
Domain1473 – 155381Sushi 5
Region272 – 583312Metalloprotease
Compositional bias24 – 8259Arg-rich

Sites

Active site5601 By similarity
Metal binding5591Zinc; catalytic By similarity
Metal binding5631Zinc; catalytic By similarity
Metal binding5691Zinc; catalytic By similarity

Amino acid modifications

Glycosylation3871N-linked (GlcNAc...) Potential
Glycosylation3981N-linked (GlcNAc...) Potential
Glycosylation4261N-linked (GlcNAc...) Potential
Glycosylation5161N-linked (GlcNAc...) Potential
Glycosylation5981N-linked (GlcNAc...) Potential
Glycosylation6161N-linked (GlcNAc...) Potential
Glycosylation7221N-linked (GlcNAc...) Potential
Glycosylation8221N-linked (GlcNAc...) Potential
Glycosylation10231N-linked (GlcNAc...) Potential
Glycosylation12191N-linked (GlcNAc...) Potential
Glycosylation12231N-linked (GlcNAc...) Potential
Glycosylation13201N-linked (GlcNAc...) Potential
Glycosylation15161N-linked (GlcNAc...) Potential
Disulfide bond141 ↔ 232 By similarity
Disulfide bond324 ↔ 619 By similarity
Disulfide bond329 ↔ 654 By similarity
Disulfide bond411 ↔ 425 By similarity
Disulfide bond421 ↔ 437 By similarity
Disulfide bond454 ↔ 470 By similarity
Disulfide bond458Interchain (with C-49 in PRG2 proform) By similarity
Disulfide bond471 ↔ 482 By similarity
Disulfide bond580 ↔ 597Or C-580 with C-609 By similarity
Disulfide bond584 ↔ 609Or C-584 with C-597 By similarity
Disulfide bond707 ↔ 875 By similarity
Disulfide bond710 ↔ 878 By similarity
Disulfide bond729Interchain (with C-170 in PRG2 proform) By similarity
Disulfide bond750 ↔ 832 By similarity
Disulfide bond772 ↔ 778 By similarity
Disulfide bond944 ↔ 972 By similarity
Disulfide bond957 ↔ 968 By similarity
Disulfide bond980 ↔ 987 By similarity
Disulfide bond996 ↔ 1008 By similarity
Disulfide bond1033 ↔ 1067 By similarity
Disulfide bond1048 ↔ 1136 By similarity
Disulfide bond1189 ↔ 1202 By similarity
Disulfide bond1207Interchain By similarity
Disulfide bond1212 ↔ 1266 By similarity
Disulfide bond1224 ↔ 1235 By similarity
Disulfide bond1239 ↔ 1277 By similarity
Disulfide bond1282 ↔ 1326 By similarity
Disulfide bond1297 ↔ 1307 By similarity
Disulfide bond1311 ↔ 1339 By similarity
Disulfide bond1343 ↔ 1396 By similarity
Disulfide bond1359 ↔ 1370 By similarity
Disulfide bond1374 ↔ 1407 By similarity
Disulfide bond1412 ↔ 1455 By similarity
Disulfide bond1425 ↔ 1435 By similarity
Disulfide bond1439 ↔ 1468 By similarity
Disulfide bond1475 ↔ 1536 By similarity
Disulfide bond1489 ↔ 1499 By similarity
Disulfide bond1503 ↔ 1551 By similarity
Disulfide bond1555 ↔ 1573 By similarity

Natural variations

Alternative sequence4901R → RQSIRKRAHVVEESWLPHGK QKAKKRKRTR in isoform 2.
VSP_012193

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 7, 2004. Version 2.
Checksum: B09404C206CB60D1

FASTA1,624181,318
        10         20         30         40         50         60 
MRLWSWVLRL GLLSAALGCG LAERPRRVRR DPRAVRPPRP AAGPATCATR AARGRRASPP 

        70         80         90        100        110        120 
PPPGGAWEAV RVPRRRQQRA ARGAEEPSPP SRALYFSGRG EQLRLRADLE LPRDAFTLQV 

       130        140        150        160        170        180 
WLRAEGGQKS PAVITGLYDK CSYTSRDRGW VMGIHTTSDQ GNRDPRYFFS LKTDRARKVT 

       190        200        210        220        230        240 
TIDAHRSYLP GQWVHLAATY DGRLMKLYMN GAQVATSAEQ VGGIFSPLTQ KCKVLMLGGS 

       250        260        270        280        290        300 
ALNHNFRGHI EHFSLWKVAR TQREIVSDME TRGLHTPLPQ LLLQENWDNV KRTWSPMKDG 

       310        320        330        340        350        360 
NSPQVEFSNA HGFLLDTNLE PPLCGQTLCD NTEVISSYNQ LPSFRQPKVV RYRVVNIYDD 

       370        380        390        400        410        420 
HHENPTVSWQ QIDFQHQQLA EAFQHYNISW ELEVLNINSS SLRHRLILAN CDISKIGDEK 

       430        440        450        460        470        480 
CDPECNHTLT GHDGGDCRQL RYPAFMKKQQ NGVCDMDCNY ERFNFDGGEC CDPDITDVTK 

       490        500        510        520        530        540 
TCFDPDSPHR AYLDVNELKN ILRLDGSTHL NIFFANSSEE ELAGVATWPW DKEALMHLGG 

       550        560        570        580        590        600 
IVLNPSFYGI PGHTHTMIHE IGHSLGLYHI FRGISEIQSC SDPCMETEPS FETGDLCNDT 

       610        620        630        640        650        660 
NPAPKHKFCG DPGPGNDTCG FHGFFNTPYN NFMSYADDDC TDSFTPNQVS RMHCYLDLVY 

       670        680        690        700        710        720 
QSWQPSRKPA PVALAPQVVG HTMDSVMLEW FPPIDGHFFE RELGSACDLC LEGRILVQYA 

       730        740        750        760        770        780 
FNASSPMPCG PSGHWSPREA EGHPDVEQPC KSSVRTWSPN SAVNPHTVPP ACPEPQGCYL 

       790        800        810        820        830        840 
ELEFRYPLVP ESLTIWVTFV SSDWDSSGAV NDIKLLTISG KNISLGPQNV FCDIPLTIRL 

       850        860        870        880        890        900 
RDVGEEVYGI QIYTLDEHLE IDAAMLTSTV DSPLCLQCKP LQYKVLRDPP LLEDVASLLH 

       910        920        930        940        950        960 
LNRRFMDTDL KLGSVYQYRI ITISGNEESE PSPAAIYTHG SGYCGDGVIQ KDQGEECDDM 

       970        980        990       1000       1010       1020 
NKVNGDGCSL FCKQEVSFNC IDEPSRCYFH DGDGMCEEFE QKTSIKDCGV YTPQGFLDQW 

      1030       1040       1050       1060       1070       1080 
ASNASVSHQD QQCPGWVVIG QPAASQVCRT KVIDLSEGIS QHAWYPCTIT YPYYHLPQTT 

      1090       1100       1110       1120       1130       1140 
FWLQTYFSQP MVAAAVIIHL VTDGTYYGDQ KQETISVQLL DTKDQSHDLG LHVLSCRNNP 

      1150       1160       1170       1180       1190       1200 
LIIPVVHDLS QPFYHSQAVH VSFSSPLVAI SGVALRSFDN FDPVTLSSCQ RGETYSPAEQ 

      1210       1220       1230       1240       1250       1260 
SCVHFACQAA DCPELAVGNA SLNCSSNHHY HGAQCTVSCQ TGYVLQIQRD DELIKSQVGP 

      1270       1280       1290       1300       1310       1320 
SITVTCTEGK WNKQVACEPV DCGIPDHHHV YAASFSCPEG TTFGRRCSFQ CRHPAQLKGN 

      1330       1340       1350       1360       1370       1380 
NSFLTCMEDG LWSFPEALCE LMCLAPPPVP NADLQTARCR ENKHKVGSFC KYKCKPGYHV 

      1390       1400       1410       1420       1430       1440 
PGSSRKSKKR AFKTQCTQDG SWQEGTCVPV TCDPPPPKFH GLYQCTNGFQ FNSECRIKCE 

      1450       1460       1470       1480       1490       1500 
DSDASQGRGS NIIHCRKDGT WSGSFHVCRE MQGQCSAPNQ LNSNLKLQCP DGYAIGSECA 

      1510       1520       1530       1540       1550       1560 
ISCLDHNSES IILPVNLTVR DIPHWMNPTR VQRIVCTAGL QWYPHPALIH CVKGCEPFMG 

      1570       1580       1590       1600       1610       1620 
DNYCDAINNR AFCNYDGGDC CTSTVKTKKV TPFPMSCDLQ NDCACRDPEA QEHNRKDLRG 


YSHG 

« Hide

Isoform 2 [UniParc].

Checksum: EF7A13AFE698A430
Show »

FASTA1,653184,839

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[2]"Expression of recombinant murine pregnancy-associated plasma protein-A (PAPP-A) and a novel variant (PAPP-Ai) with differential proteolytic activity."
Soe R., Overgaard M.T., Thomsen A.R., Laursen L.S., Olsen I.M., Sottrup-Jensen L., Haaning J., Giudice L.C., Conover C.A., Oxvig C.
Eur. J. Biochem. 269:2247-2256(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 80-1624 (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY.
[3]"Differential regulation of pregnancy associated plasma protein (PAPP)-A during pregnancy in human and mouse."
Qin X., Sexton C., Byun D., Strong D.D., Baylink D.J., Mohan S.
Growth Horm. IGF Res. 12:359-366(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 136-489 (ISOFORM 1).
Strain: 129/SvJ.
[4]"The regulated expression of the pregnancy-associated plasma protein-A in the rodent ovary: a proposed role in the development of dominant follicles and of corpora lutea."
Hourvitz A., Kuwahara A., Hennebold J.D., Tavares A.B., Negishi H., Lee T.H., Erickson G.F., Adashi E.Y.
Endocrinology 143:1833-1844(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 258-1624 (ISOFORM 1), TISSUE SPECIFICITY.
Strain: C57BL/6J.
[5]"Partial sequence of Mus musculus Mus musculus pregnancy-associated plasma protein A (Pappa)."
Olesen C., Hansen C., Hayashizaki Y., Byskov A., Tommerup N.
Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1157-1624 (ISOFORM 1).
Strain: C57BL/6J.
Tissue: Embryo.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS18267.1. [Q8R4K8-1]
RefSeqNP_067337.1. NM_021362.1. [Q8R4K8-1]
UniGeneMm.317854.

3D structure databases

ProteinModelPortalQ8R4K8.
SMRQ8R4K8. Positions 540-657, 1225-1509.
ModBaseSearch...
MobiDBSearch...

Protein family/group databases

MEROPSM43.004.

PTM databases

PhosphoSiteQ8R4K8.

Proteomic databases

PaxDbQ8R4K8.
PRIDEQ8R4K8.

Protocols and materials databases

DNASU18491.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000084501; ENSMUSP00000081545; ENSMUSG00000028370. [Q8R4K8-1]
GeneID18491.
KEGGmmu:18491.
UCSCuc008thm.1. mouse. [Q8R4K8-1]
uc012dgb.1. mouse. [Q8R4K8-2]

Organism-specific databases

CTD5069.
MGIMGI:97479. Pappa.

Phylogenomic databases

eggNOGNOG128309.
GeneTreeENSGT00390000009007.
HOVERGENHBG053501.
KOK07762.
OMAGIQIYTL.
OrthoDBEOG7HB58B.
PhylomeDBQ8R4K8.
TreeFamTF331636.

Gene expression databases

BgeeQ8R4K8.
CleanExMM_PAPPA.
GenevestigatorQ8R4K8.

Family and domain databases

Gene3D2.60.120.200. 1 hit.
3.40.390.10. 1 hit.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR006558. LamG-like.
IPR024079. MetalloPept_cat_dom.
IPR011936. Myxo_disulph_rpt.
IPR000800. Notch_dom.
IPR008754. Peptidase_M43.
IPR000436. Sushi_SCR_CCP.
[Graphical view]
PfamPF00066. Notch. 2 hits.
PF05572. Peptidase_M43. 1 hit.
PF00084. Sushi. 3 hits.
[Graphical view]
SMARTSM00032. CCP. 4 hits.
SM00560. LamGL. 1 hit.
SM00004. NL. 3 hits.
[Graphical view]
SUPFAMSSF49899. SSF49899. 1 hit.
SSF57535. SSF57535. 4 hits.
TIGRFAMsTIGR02232. myxo_disulf_rpt. 1 hit.
PROSITEPS50923. SUSHI. 5 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio294210.
PROQ8R4K8.
SOURCESearch...

Entry information

Entry namePAPP1_MOUSE
AccessionPrimary (citable) accession number: Q8R4K8
Secondary accession number(s): Q80VW3 expand/collapse secondary AC list , Q80YY1, Q8K423, Q8R4K7, Q9ES06, Q9JK57
Entry history
Integrated into UniProtKB/Swiss-Prot: December 7, 2004
Last sequence update: December 7, 2004
Last modified: July 9, 2014
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot