Seroatlas · Human Serome Atlas

PAPPA

Pappalysin-1

Also known as: ASBABP2, DIPLA1, IGFBP-4ase, PAPA, PAPP-A, PAPP1_HUMAN, PAPPA1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q13219
Gene: PAPPA
Ensembl: ENSG00000182752
Chromosome: 9
Canonical length: 1627 aa
Protein class: Cancer-related genes, Candidate cardiovascular disease genes, Enzymes, Plasma proteins, Predicted secreted proteins
Secretome location: Secreted in female reproductive system
Quaternary structure: Homodimer

OverviewNCBI Gene

This gene encodes a secreted metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs). Following IGFBP cleavage, insulin growth factors dissociate from IGFBPs and bind to IGF receptors, resulting in activation of the IGF pathway. The encoded protein plays a role in bone formation, inflammation, wound healing and female fertility. Enhanced expression of this protein is associated with diabetic nephropathy in human patients and this protein may promote tumor invasion and growth in various human cancers. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

1627 residues, UniProt reviewed canonical sequence.

>Q13219|PAPPA
     1  MRLWSWVLHL GLLSAALGCG LAERPRRARR DPRAGRPPRP AAGPATCATR AARGRRASPP
    61  PPPPPGGAWE AVRVPRRRQQ REARGATEEP SPPSRALYFS GRGEQLRLRA DLELPRDAFT
   121  LQVWLRAEGG QRSPAVITGL YDKCSYISRD RGWVVGIHTI SDQDNKDPRY FFSLKTDRAR
   181  QVTTINAHRS YLPGQWVYLA ATYDGQFMKL YVNGAQVATS GEQVGGIFSP LTQKCKVLML
   241  GGSALNHNYR GYIEHFSLWK VARTQREILS DMETHGAHTA LPQLLLQENW DNVKHAWSPM
   301  KDGSSPKVEF SNAHGFLLDT SLEPPLCGQT LCDNTEVIAS YNQLSSFRQP KVVRYRVVNL
   361  YEDDHKNPTV TREQVDFQHH QLAEAFKQYN ISWELDVLEV SNSSLRRRLI LANCDISKIG
   421  DENCDPECNH TLTGHDGGDC RHLRHPAFVK KQHNGVCDMD CNYERFNFDG GECCDPEITN
   481  VTQTCFDPDS PHRAYLDVNE LKNILKLDGS THLNIFFAKS SEEELAGVAT WPWDKEALMH
   541  LGGIVLNPSF YGMPGHTHTM IHEIGHSLGL YHVFRGISEI QSCSDPCMET EPSFETGDLC
   601  NDTNPAPKHK SCGDPGPGND TCGFHSFFNT PYNNFMSYAD DDCTDSFTPN QVARMHCYLD
   661  LVYQGWQPSR KPAPVALAPQ VLGHTTDSVT LEWFPPIDGH FFERELGSAC HLCLEGRILV
   721  QYASNASSPM PCSPSGHWSP REAEGHPDVE QPCKSSVRTW SPNSAVNPHT VPPACPEPQG
   781  CYLELEFLYP LVPESLTIWV TFVSTDWDSS GAVNDIKLLA VSGKNISLGP QNVFCDVPLT
   841  IRLWDVGEEV YGIQIYTLDE HLEIDAAMLT STADTPLCLQ CKPLKYKVVR DPPLQMDVAS
   901  ILHLNRKFVD MDLNLGSVYQ YWVITISGTE ESEPSPAVTY IHGSGYCGDG IIQKDQGEQC
   961  DDMNKINGDG CSLFCRQEVS FNCIDEPSRC YFHDGDGVCE EFEQKTSIKD CGVYTPQGFL
  1021  DQWASNASVS HQDQQCPGWV IIGQPAASQV CRTKVIDLSE GISQHAWYPC TISYPYSQLA
  1081  QTTFWLRAYF SQPMVAAAVI VHLVTDGTYY GDQKQETISV QLLDTKDQSH DLGLHVLSCR
  1141  NNPLIIPVVH DLSQPFYHSQ AVRVSFSSPL VAISGVALRS FDNFDPVTLS SCQRGETYSP
  1201  AEQSCVHFAC EKTDCPELAV ENASLNCSSS DRYHGAQCTV SCRTGYVLQI RRDDELIKSQ
  1261  TGPSVTVTCT EGKWNKQVAC EPVDCSIPDH HQVYAASFSC PEGTTFGSQC SFQCRHPAQL
  1321  KGNNSLLTCM EDGLWSFPEA LCELMCLAPP PVPNADLQTA RCRENKHKVG SFCKYKCKPG
  1381  YHVPGSSRKS KKRAFKTQCT QDGSWQEGAC VPVTCDPPPP KFHGLYQCTN GFQFNSECRI
  1441  KCEDSDASQG LGSNVIHCRK DGTWNGSFHV CQEMQGQCSV PNELNSNLKL QCPDGYAIGS
  1501  ECATSCLDHN SESIILPMNV TVRDIPHWLN PTRVERVVCT AGLKWYPHPA LIHCVKGCEP
  1561  FMGDNYCDAI NNRAFCNYDG GDCCTSTVKT KKVTPFPMSC DLQGDCACRD PQAQEHSRKD
  1621  LRGYSHG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PAPPA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.29
Highest tissue expression: 68 nTPM

Expression across tissuesHPA

Tissue

placenta: 68 nTPM
parathyroid gland: 8.6 nTPM
urinary bladder: 4.2 nTPM
cervix: 3.9 nTPM
smooth muscle: 3.9 nTPM
adipose tissue: 3.8 nTPM

Single-cell type

renal collecting duct principal cells: 731 nCPM
renal connecting tubule cells: 358 nCPM
endometrial stromal cells: 334 nCPM
mesothelial cells: 263 nCPM
decidual stromal cells: 226 nCPM
epicardial cells: 218 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

medulla oblongata: 7.3 nTPM
midbrain: 7.2 nTPM
choroid plexus: 6.4 nTPM
pons: 6.1 nTPM
thalamus: 5.4 nTPM
hypothalamus: 5.2 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.35
gnomAD pLI: 0.16
gnomAD missense Z: 2.21
DepMap mean gene effect: -0.08
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of PAPPA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

PRG2

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads PAPPA as an antibody target. Whether an autoantibody or antibody against PAPPA could matter depends on whether native PAPPA is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

PAPPA is annotated as secreted, so native PAPPA circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label PAPPA as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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