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Q8R4K8

- PAPP1_MOUSE

UniProt

Q8R4K8 - PAPP1_MOUSE

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Protein

Pappalysin-1

Gene
Pappa
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

Binds 1 zinc ion per subunit By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi559 – 5591Zinc; catalytic By similarity
Active sitei560 – 5601 By similarity
Metal bindingi563 – 5631Zinc; catalytic By similarity
Metal bindingi569 – 5691Zinc; catalytic By similarity

GO - Molecular functioni

  1. endopeptidase activity Source: MGI
  2. metal ion binding Source: UniProtKB-KW
  3. metallopeptidase activity Source: UniProtKB-KW

GO - Biological processi

  1. cell differentiation Source: InterPro
  2. response to follicle-stimulating hormone Source: Ensembl
  3. response to glucocorticoid Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

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
ProteomesiUP000000589: Chromosome 4

Organism-specific databases

MGIiMGI:97479. Pappa.

Subcellular locationi

GO - Cellular componenti

  1. extracellular space Source: Ensembl
  2. membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222 Reviewed predictionAdd
BLAST
Propeptidei23 – 8058 By similarityPRO_0000029247Add
BLAST
Chaini81 – 16241544Pappalysin-1PRO_0000029248Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi141 ↔ 232 By similarity
Disulfide bondi324 ↔ 619 By similarity
Disulfide bondi329 ↔ 654 By similarity
Glycosylationi387 – 3871N-linked (GlcNAc...) Reviewed prediction
Glycosylationi398 – 3981N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi411 ↔ 425 By similarity
Disulfide bondi421 ↔ 437 By similarity
Glycosylationi426 – 4261N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi454 ↔ 470 By similarity
Disulfide bondi458 – 458Interchain (with C-49 in PRG2 proform) By similarity
Disulfide bondi471 ↔ 482 By similarity
Glycosylationi516 – 5161N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi580 ↔ 597Or C-580 with C-609 By similarity
Disulfide bondi584 ↔ 609Or C-584 with C-597 By similarity
Glycosylationi598 – 5981N-linked (GlcNAc...) Reviewed prediction
Glycosylationi616 – 6161N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi707 ↔ 875 By similarity
Disulfide bondi710 ↔ 878 By similarity
Glycosylationi722 – 7221N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi729 – 729Interchain (with C-170 in PRG2 proform) By similarity
Disulfide bondi750 ↔ 832 By similarity
Disulfide bondi772 ↔ 778 By similarity
Glycosylationi822 – 8221N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi944 ↔ 972 By similarity
Disulfide bondi957 ↔ 968 By similarity
Disulfide bondi980 ↔ 987 By similarity
Disulfide bondi996 ↔ 1008 By similarity
Glycosylationi1023 – 10231N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1033 ↔ 1067 By similarity
Disulfide bondi1048 ↔ 1136 By similarity
Disulfide bondi1189 ↔ 1202 By similarity
Disulfide bondi1207 – 1207Interchain By similarity
Disulfide bondi1212 ↔ 1266 By similarity
Glycosylationi1219 – 12191N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1223 – 12231N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1224 ↔ 1235 By similarity
Disulfide bondi1239 ↔ 1277 By similarity
Disulfide bondi1282 ↔ 1326 By similarity
Disulfide bondi1297 ↔ 1307 By similarity
Disulfide bondi1311 ↔ 1339 By similarity
Glycosylationi1320 – 13201N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1343 ↔ 1396 By similarity
Disulfide bondi1359 ↔ 1370 By similarity
Disulfide bondi1374 ↔ 1407 By similarity
Disulfide bondi1412 ↔ 1455 By similarity
Disulfide bondi1425 ↔ 1435 By similarity
Disulfide bondi1439 ↔ 1468 By similarity
Disulfide bondi1475 ↔ 1536 By similarity
Disulfide bondi1489 ↔ 1499 By similarity
Disulfide bondi1503 ↔ 1551 By similarity
Glycosylationi1516 – 15161N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1555 ↔ 1573 By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ8R4K8.
PRIDEiQ8R4K8.

PTM databases

PhosphoSiteiQ8R4K8.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ8R4K8.
CleanExiMM_PAPPA.
GenevestigatoriQ8R4K8.

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.

Structurei

3D structure databases

ProteinModelPortaliQ8R4K8.
SMRiQ8R4K8. Positions 540-657, 1225-1509.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1210 – 127970Sushi 1Add
BLAST
Domaini1280 – 134162Sushi 2Add
BLAST
Domaini1342 – 140968Sushi 3Add
BLAST
Domaini1410 – 147061Sushi 4Add
BLAST
Domaini1473 – 155381Sushi 5Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni272 – 583312MetalloproteaseAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi24 – 8259Arg-richAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase M43B family.

Keywords - Domaini

Repeat, Signal, Sushi

Phylogenomic databases

eggNOGiNOG128309.
GeneTreeiENSGT00390000009007.
HOVERGENiHBG053501.
KOiK07762.
OMAiGIQIYTL.
OrthoDBiEOG7HB58B.
PhylomeDBiQ8R4K8.
TreeFamiTF331636.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR008985. 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]
PfamiPF00066. Notch. 2 hits.
PF05572. 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. Align

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

MRLWSWVLRL GLLSAALGCG LAERPRRVRR DPRAVRPPRP AAGPATCATR     50
AARGRRASPP PPPGGAWEAV RVPRRRQQRA ARGAEEPSPP SRALYFSGRG 100
EQLRLRADLE LPRDAFTLQV WLRAEGGQKS PAVITGLYDK CSYTSRDRGW 150
VMGIHTTSDQ GNRDPRYFFS LKTDRARKVT TIDAHRSYLP GQWVHLAATY 200
DGRLMKLYMN GAQVATSAEQ VGGIFSPLTQ KCKVLMLGGS ALNHNFRGHI 250
EHFSLWKVAR TQREIVSDME TRGLHTPLPQ LLLQENWDNV KRTWSPMKDG 300
NSPQVEFSNA HGFLLDTNLE PPLCGQTLCD NTEVISSYNQ LPSFRQPKVV 350
RYRVVNIYDD HHENPTVSWQ QIDFQHQQLA EAFQHYNISW ELEVLNINSS 400
SLRHRLILAN CDISKIGDEK CDPECNHTLT GHDGGDCRQL RYPAFMKKQQ 450
NGVCDMDCNY ERFNFDGGEC CDPDITDVTK TCFDPDSPHR AYLDVNELKN 500
ILRLDGSTHL NIFFANSSEE ELAGVATWPW DKEALMHLGG IVLNPSFYGI 550
PGHTHTMIHE IGHSLGLYHI FRGISEIQSC SDPCMETEPS FETGDLCNDT 600
NPAPKHKFCG DPGPGNDTCG FHGFFNTPYN NFMSYADDDC TDSFTPNQVS 650
RMHCYLDLVY QSWQPSRKPA PVALAPQVVG HTMDSVMLEW FPPIDGHFFE 700
RELGSACDLC LEGRILVQYA FNASSPMPCG PSGHWSPREA EGHPDVEQPC 750
KSSVRTWSPN SAVNPHTVPP ACPEPQGCYL ELEFRYPLVP ESLTIWVTFV 800
SSDWDSSGAV NDIKLLTISG KNISLGPQNV FCDIPLTIRL RDVGEEVYGI 850
QIYTLDEHLE IDAAMLTSTV DSPLCLQCKP LQYKVLRDPP LLEDVASLLH 900
LNRRFMDTDL KLGSVYQYRI ITISGNEESE PSPAAIYTHG SGYCGDGVIQ 950
KDQGEECDDM NKVNGDGCSL FCKQEVSFNC IDEPSRCYFH DGDGMCEEFE 1000
QKTSIKDCGV YTPQGFLDQW ASNASVSHQD QQCPGWVVIG QPAASQVCRT 1050
KVIDLSEGIS QHAWYPCTIT YPYYHLPQTT FWLQTYFSQP MVAAAVIIHL 1100
VTDGTYYGDQ KQETISVQLL DTKDQSHDLG LHVLSCRNNP LIIPVVHDLS 1150
QPFYHSQAVH VSFSSPLVAI SGVALRSFDN FDPVTLSSCQ RGETYSPAEQ 1200
SCVHFACQAA DCPELAVGNA SLNCSSNHHY HGAQCTVSCQ TGYVLQIQRD 1250
DELIKSQVGP SITVTCTEGK WNKQVACEPV DCGIPDHHHV YAASFSCPEG 1300
TTFGRRCSFQ CRHPAQLKGN NSFLTCMEDG LWSFPEALCE LMCLAPPPVP 1350
NADLQTARCR ENKHKVGSFC KYKCKPGYHV PGSSRKSKKR AFKTQCTQDG 1400
SWQEGTCVPV TCDPPPPKFH GLYQCTNGFQ FNSECRIKCE DSDASQGRGS 1450
NIIHCRKDGT WSGSFHVCRE MQGQCSAPNQ LNSNLKLQCP DGYAIGSECA 1500
ISCLDHNSES IILPVNLTVR DIPHWMNPTR VQRIVCTAGL QWYPHPALIH 1550
CVKGCEPFMG DNYCDAINNR AFCNYDGGDC CTSTVKTKKV TPFPMSCDLQ 1600
NDCACRDPEA QEHNRKDLRG YSHG 1624
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei490 – 4901R → RQSIRKRAHVVEESWLPHGK QKAKKRKRTR in isoform 2. VSP_012193

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS18267.1. [Q8R4K8-1 ]
RefSeqi NP_067337.1. NM_021362.1. [Q8R4K8-1 ]
UniGenei Mm.317854.

3D structure databases

ProteinModelPortali Q8R4K8.
SMRi Q8R4K8. Positions 540-657, 1225-1509.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

MEROPSi M43.004.

PTM databases

PhosphoSitei Q8R4K8.

Proteomic databases

PaxDbi Q8R4K8.
PRIDEi Q8R4K8.

Protocols and materials databases

DNASUi 18491.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000084501 ; ENSMUSP00000081545 ; ENSMUSG00000028370 . [Q8R4K8-1 ]
GeneIDi 18491.
KEGGi mmu:18491.
UCSCi uc008thm.1. mouse. [Q8R4K8-1 ]
uc012dgb.1. mouse. [Q8R4K8-2 ]

Organism-specific databases

CTDi 5069.
MGIi MGI:97479. Pappa.

Phylogenomic databases

eggNOGi NOG128309.
GeneTreei ENSGT00390000009007.
HOVERGENi HBG053501.
KOi K07762.
OMAi GIQIYTL.
OrthoDBi EOG7HB58B.
PhylomeDBi Q8R4K8.
TreeFami TF331636.

Miscellaneous databases

NextBioi 294210.
PROi Q8R4K8.
SOURCEi Search...

Gene expression databases

Bgeei Q8R4K8.
CleanExi MM_PAPPA.
Genevestigatori Q8R4K8.

Family and domain databases

Gene3Di 2.60.120.200. 1 hit.
3.40.390.10. 1 hit.
InterProi IPR008985. 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 ]
Pfami PF00066. Notch. 2 hits.
PF05572. Peptidase_M43. 1 hit.
PF00084. Sushi. 3 hits.
[Graphical view ]
SMARTi SM00032. CCP. 4 hits.
SM00560. LamGL. 1 hit.
SM00004. NL. 3 hits.
[Graphical view ]
SUPFAMi SSF49899. SSF49899. 1 hit.
SSF57535. SSF57535. 4 hits.
TIGRFAMsi TIGR02232. myxo_disulf_rpt. 1 hit.
PROSITEi PS50923. SUSHI. 5 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.

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: July 9, 2014
This is version 100 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

External Data

Dasty 3

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