Reviewed,
UniProtKB/Swiss-Prot Q13219 (PAPP1_HUMAN)
Last modified
February 9, 2010.
Version 116.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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Names and origin
| Protein names | Recommended name: Pappalysin-1 EC=3.4.24.79 Alternative name(s): Pregnancy-associated plasma protein A Short name=PAPP-A Insulin-like growth factor-dependent IGF-binding protein 4 protease Short name=IGF-dependent IGFBP-4 protease Short name=IGFBP-4ase | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1627 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein 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. Ref.7 Ref.8 Ref.12 |
| 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. |
| Enzyme regulation | Inhibited by complexation with the proform of PRG2. Ref.8 |
| Subunit structure | Homodimer; disulfide-linked. In pregnancy serum, predominantly found as a disulfide-linked 2:2 heterotetramer with the proform of PRG2. Ref.8 Ref.5 Ref.6 |
| Subcellular location | |
| Tissue specificity | 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. Ref.7 Ref.4 Ref.9 Ref.10 |
| Developmental stage | Present in serum and placenta during pregnancy; levels increase throughout pregnancy. Ref.10 Ref.11 |
| Induction | |
| Post-translational modification | There appear to be no free sulfhydryl groups. |
| Sequence similarities | Belongs to the peptidase M43B family. Contains 5 Sushi (CCP/SCR) domains. |
| Sequence caution | The sequence AAC50543.1 differs from that shown. Reason: Frameshift at positions 51 and 67. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Secreted |
| Coding sequence diversity | Polymorphism |
| Domain | Repeat Signal Sushi |
| Ligand | Metal-binding Zinc |
| Molecular function | Hydrolase Metalloprotease Protease |
| PTM | Disulfide bond Glycoprotein Zymogen |
| Technical term | Complete proteome Direct protein sequencing |
| Gene Ontology (GO) | |
| Biological process | cell differentiation Inferred from electronic annotation. Source: InterPro female pregnancy Ref.7 Ref.8Non-traceable author statement. Source: UniProtKB |
| Cellular component | extracellular region Ref.7 Ref.8 Inferred from direct assay. Source: UniProtKB membraneInferred from electronic annotation. Source: InterPro |
| Molecular function | metallopeptidase activity Ref.7 Ref.8 Inferred from direct assay. Source: UniProtKB zinc ion binding Ref.4 Ref.7 Ref.8Non-traceable author statement. Source: UniProtKB |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 22 | 22 | Potential | ||||||||
| Propeptide | 23 – 80 | 58 | PRO_0000029245 | ||||||||
| Chain | 81 – 1627 | 1547 | Pappalysin-1 | PRO_0000029246 | |||||||
Regions | |||||||||||
| Domain | 1213 – 1282 | 70 | Sushi 1 | ||||||||
| Domain | 1283 – 1344 | 62 | Sushi 2 | ||||||||
| Domain | 1345 – 1412 | 68 | Sushi 3 | ||||||||
| Domain | 1413 – 1473 | 61 | Sushi 4 | ||||||||
| Domain | 1476 – 1556 | 81 | Sushi 5 | ||||||||
| Region | 272 – 583 | 312 | Metalloprotease | ||||||||
| Compositional bias | 24 – 84 | 61 | Arg-rich | ||||||||
Sites | |||||||||||
| Active site | 563 | 1 | By similarity | ||||||||
| Metal binding | 562 | 1 | Zinc; catalytic By similarity | ||||||||
| Metal binding | 566 | 1 | Zinc; catalytic By similarity | ||||||||
| Metal binding | 572 | 1 | Zinc; catalytic By similarity | ||||||||
Amino acid modifications | |||||||||||
| Glycosylation | 390 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 402 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 429 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 480 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 601 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 619 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 725 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 825 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1026 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 1222 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1226 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 1323 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Glycosylation | 1465 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 1519 | 1 | N-linked (GlcNAc...) Ref.6 | ||||||||
| Disulfide bond | 144 ↔ 235 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 327 ↔ 622 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 332 ↔ 657 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 414 ↔ 428 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 424 ↔ 440 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 457 ↔ 473 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 461 | Interchain (with C-51 in PRG2 proform) Ref.5 Ref.6 | |||||||||
| Disulfide bond | 474 ↔ 485 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 583 ↔ 600 | Or C-583 with C-612 Ref.5 Ref.6 | |||||||||
| Disulfide bond | 587 ↔ 612 | Or C-587 with C-600 Ref.5 Ref.6 | |||||||||
| Disulfide bond | 710 ↔ 878 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 713 ↔ 881 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 732 | Interchain (with C-169 in PRG2 proform) Ref.5 Ref.6 | |||||||||
| Disulfide bond | 753 ↔ 835 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 775 ↔ 781 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 947 ↔ 975 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 960 ↔ 971 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 983 ↔ 990 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 999 ↔ 1011 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1036 ↔ 1070 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1051 ↔ 1139 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1192 ↔ 1205 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1210 | Interchain Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1215 ↔ 1269 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1227 ↔ 1238 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1242 ↔ 1280 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1285 ↔ 1329 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1300 ↔ 1310 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1314 ↔ 1342 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1346 ↔ 1399 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1362 ↔ 1373 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1377 ↔ 1410 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1415 ↔ 1458 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1428 ↔ 1438 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1442 ↔ 1471 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1478 ↔ 1539 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1492 ↔ 1502 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1506 ↔ 1554 | Ref.5 Ref.6 | |||||||||
| Disulfide bond | 1558 ↔ 1576 | Ref.5 Ref.6 | |||||||||
Natural variations | |||||||||||
| Natural variant | 5 | 1 | S → I: dbSNP rs417012. | VAR_057091 | |||||||
| Natural variant | 325 | 1 | P → L: dbSNP rs445159. | VAR_057092 | |||||||
| Natural variant | 944 | 1 | S → R | VAR_011419 | |||||||
| Natural variant | 1224 | 1 | S → Y: dbSNP rs7020782. Ref.3 Ref.13 | VAR_018726 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 107 | 1 | R → RV in AAC50543. Ref.1 | ||||||||
| Sequence conflict | 107 | 1 | R → RV in CAA48341. Ref.4 | ||||||||
| Sequence conflict | 511 – 512 | 2 | TH → RD AA sequence Ref.4 | ||||||||
| Sequence conflict | 1622 | 1 | R → Q in AAH78657. Ref.3 | ||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Complete cDNA sequence of the preproform of human pregnancy-associated plasma protein-A. Evidence for expression in the brain and induction by cAMP." Haaning J., Oxvig C., Overgaard M.T., Ebbesen P., Kristensen T., Sottrup-Jensen L. Eur. J. Biochem. 237:159-163(1996) [PubMed: 8620868] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, VARIANT ARG-944. Tissue: Placenta. |
| [2] | "DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. Dunham I.Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TYR-1224. Tissue: Placenta. |
| [4] | "Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA." Kristensen T., Oxvig C., Sand O., Moller N.P.H., Sottrup-Jensen L. Biochemistry 33:1592-1598(1994) [PubMed: 7508748] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 77-1627, PROTEIN SEQUENCE OF 81-98; 117-126; 210-224; 466-485; 507-519; 576-593; 609-621; 718-736; 742-754; 1006-1017; 1259-1273; 1369-1374; 1389-1398; 1490-1509; 1524-1533 AND 1537-1544, VARIANT ARG-944, TISSUE SPECIFICITY. Tissue: Placenta and Serum. |
| [5] | "Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein." Oxvig C., Sand O., Kristensen T., Gleich G.J., Sottrup-Jensen L. J. Biol. Chem. 268:12243-12246(1993) [PubMed: 7685339] [Abstract] Cited for: PROTEIN SEQUENCE OF 81-89; 117-126; 210-224; 460-485; 507-519; 576-593; 718-736; 742-754; 1259-1273; 1369-1374; 1490-1509; 1524-1533 AND 1537-1544, SUBUNIT, INTERCHAIN DISULFIDE BOND. Tissue: Serum. |
| [6] | "Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment sites." Overgaard M.T., Sorensen E.S., Stachowiak D., Boldt H.B., Kristensen L., Sottrup-Jensen L., Oxvig C. J. Biol. Chem. 278:2106-2117(2003) [PubMed: 12421832] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-402; ASN-429; ASN-480; ASN-601; ASN-619; ASN-725; ASN-1026; ASN-1226; ASN-1323 AND ASN-1519, DISULFIDE BONDS. |
| [7] | "The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A." Lawrence J.B., Oxvig C., Overgaard M.T., Sottrup-Jensen L., Gleich G.J., Hays L.G., Yates J.R. III, Conover C.A. Proc. Natl. Acad. Sci. U.S.A. 96:3149-3153(1999) [PubMed: 10077652] [Abstract] Cited for: IDENTIFICATION, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Fibroblast. |
| [8] | "Expression of recombinant human pregnancy-associated plasma protein-A and identification of the proform of eosinophil major basic protein as its physiological inhibitor." Overgaard M.T., Haaning J., Boldt H.B., Olsen I.M., Laursen L.S., Christiansen M., Gleich G.J., Sottrup-Jensen L., Conover C.A., Oxvig C. J. Biol. Chem. 275:31128-31133(2000) [PubMed: 10913121] [Abstract] Cited for: FUNCTION, SUBUNIT, ENZYME REGULATION. |
| [9] | "Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta." Bonno M., Oxvig C., Kephart G.M., Wagner J.M., Kristensen T., Sottrup-Jensen L., Gleich G.J. Lab. Invest. 71:560-566(1994) [PubMed: 7526035] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [10] | "Messenger ribonucleic acid levels of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein: expression in human reproductive and nonreproductive tissues." Overgaard M.T., Oxvig C., Christiansen M., Lawrence J.B., Conover C.A., Gleich G.J., Sottrup-Jensen L., Haaning J. Biol. Reprod. 61:1083-1089(1999) [PubMed: 10491647] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. |
| [11] | "Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma." Oxvig C., Haaning J., Kristensen L., Wagner J.M., Rubin I., Stigbrand T., Gleich G.J., Sottrup-Jensen L. J. Biol. Chem. 270:13645-13651(1995) [PubMed: 7539791] [Abstract] Cited for: DEVELOPMENTAL STAGE. |
| [12] | "Pregnancy-associated plasma protein-A (PAPP-A) cleaves insulin-like growth factor binding protein (IGFBP)-5 independent of IGF: implications for the mechanism of IGFBP-4 proteolysis by PAPP-A." Laursen L.S., Overgaard M.T., Soe R., Boldt H.B., Sottrup-Jensen L., Giudice L.C., Conover C.A., Oxvig C. FEBS Lett. 504:36-40(2001) [PubMed: 11522292] [Abstract] Cited for: FUNCTION. |
| [13] | "Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene." Frosk P., Weiler T., Nylen E., Sudha T., Greenberg C.R., Morgan K., Fujiwara T.M., Wrogemann K. Am. J. Hum. Genet. 70:663-672(2002) [PubMed: 11822024] [Abstract] Cited for: VARIANT TYR-1224. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | U28727 mRNA. Translation: AAC50543.1. Frameshift. AL353141, AL137024, AL691426 Genomic DNA. Translation: CAI16083.1. AL691426, AL137024, AL353141 Genomic DNA. Translation: CAI16715.1. BC078657 mRNA. Translation: AAH78657.1. X68280 mRNA. Translation: CAA48341.1. |
| IPI | IPI00001869. |
| PIR | S65464. |
| RefSeq | NP_002572.2. |
| UniGene | Hs.643599 Hs.713596 |
3D structure databases | |
| SMR | Q13219. Positions 352-660, 1215-1509. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q13219. |
Protein family/group databases | |
| MEROPS | M43.004. |
Proteomic databases | |
| PRIDE | Q13219. |
Genome annotation databases | |
| Ensembl | ENST00000328252; ENSP00000330658; ENSG00000182752; Homo sapiens. [Genome view] |
| GeneID | 5069. |
| KEGG | hsa:5069. |
Organism-specific databases | |
| CTD | 5069. |
| GeneCards | GC09P117955. |
| HGNC | HGNC:8602. PAPPA. |
| HPA | CAB016724. HPA001667. |
| MIM | 176385. gene. |
| PharmGKB | PA32935. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG11817. |
| HOGENOM | HBG447260. |
| HOVERGEN | Q13219. |
| InParanoid | Q13219. |
| OMA | DPRYFFS. |
| OrthoDB | EOG9QRKQN. |
| PhylomeDB | Q13219. |
Enzyme and pathway databases | |
| BRENDA | 3.4.24.79. 247. |
| Reactome | REACT_15380. Diabetes pathways. |
Gene expression databases | |
| ArrayExpress | Q13219. |
| Bgee | Q13219. |
| CleanEx | HS_PAPPA. |
| Genevestigator | Q13219. |
| GermOnline | ENSG00000182752. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016060. Complement_control_module. IPR008985. ConA-like_lec_gl. IPR006558. LamG-like. IPR011936. Myxo_disulph_rpt. IPR000800. Notch_dom. IPR000436. Sushi_SCR_CCP. [Graphical view] |
| Gene3D | G3DSA:2.10.70.10. Complement_control_module. 1 hit. |
| Pfam | PF00066. Notch. 2 hits. PF00084. Sushi. 3 hits. [Graphical view] |
| SMART | SM00032. CCP. 4 hits. SM00560. LamGL. 1 hit. SM00004. NL. 3 hits. [Graphical view] |
| TIGRFAMs | TIGR02232. myxo_disulf_rpt. 1 hit. |
| PROSITE | PS50923. SUSHI. 5 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 19534. |
| PMAP-CutDB | Q13219. |
| SOURCE | Search... |
Entry information
| Entry name | PAPP1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13219 Secondary accession number(s): B1AMF9 Q9UDK7 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any 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. | ||||||||
Relevant documents
| Human chromosome 9 Human chromosome 9: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with


