REG1A

Pancreatic Stone Protein (PSP), also known as Lithostathine-1-alpha islet cells regeneration factor (ICRF) or islet of Langerhans regenerating protein (REG) is a protein that in humans is encoded by the REG1A gene as a single polypeptide of 144 amino acids further cleaved by trypsin to produce a 133 amino acid protein that is O-linked glycosylated on threonine 27. This protein is a type I subclass member of the Regenerating protein family. The Reg protein family is a multi protein family grouped into four subclasses, types I, II, III and IV based on the primary structures of the proteins. Reg family members REG1B, REGL, PAP and this gene are tandemly clustered on chromosome 2p12 and may have arisen from the same ancestral gene by gene duplication. The PSP is mostly produced in Human by the acinar cells of the pancreas and is secreted in the duodenum by the same pathway that pancreatic exocrine enzymes. It has C-terminal C-type lectin domain whose binding partner is currently unknown.

REG1A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1LIT, 1QDD
Identifiers
Aliases	REG1A, ICRF, P19, PSP, PSPS, PSPS1, PTP, REG, regenerating family member 1 alpha
External IDs	OMIM: 167770; MGI: 97895; HomoloGene: 68282; GeneCards: REG1A; OMA:REG1A - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2p12 Start 79,120,362 bp End 79,123,409 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in body of pancreas islet of Langerhans beta cell duodenum mucosa of ileum jejunal mucosa pancreatic ductal cell pylorus gallbladder cardia n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function carbohydrate binding growth factor activity transmembrane signaling receptor activity signaling receptor binding phosphatase binding protein phosphatase binding identical protein binding protein homodimerization activity peptidoglycan binding oligosaccharide binding Cellular component extracellular region extracellular exosome extracellular space cytosol growth cone dendrite membrane neuronal cell body membrane protein-containing complex zymogen granule basal part of cell perinuclear region of cytoplasm Biological process positive regulation of cell population proliferation regulation of signaling receptor activity response to hypoxia midgut development negative regulation of cell population proliferation positive regulation of gene expression response to organic cyclic compound response to nutrient levels wound healing response to peptide hormone cell wall disruption in other organism protein homooligomerization protein homotetramerization calcium ion homeostasis antimicrobial humoral immune response mediated by antimicrobial peptide liver regeneration response to acetylsalicylate positive regulation of dendrite extension positive regulation of type B pancreatic cell proliferation positive regulation of acinar cell proliferation response to water-immersion restraint stress pancreas regeneration response to growth hormone-releasing hormone response to gastrin cellular response to chemokine cellular response to gastrin signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5967 19692 Ensembl ENSG00000115386 n/a UniProt P05451 P43137 RefSeq (mRNA) NM_002909 NM_009042 RefSeq (protein) NP_002900 NP_033068 Location (UCSC) Chr 2: 79.12 – 79.12 Mb n/a PubMed search
Wikidata
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Function

Pancreas development and regeneration

The PSP has been shown to be associated with islet cell regeneration and diabetogenesis and may be involved in pancreatic lithogenesis (creation of pancreatic stones; pancreatic calculi).

Sepsis

The blood PSP concentration has been shown to increase substantially in response to a sepsis event. Consequently, the use of the PSP as a biomarker of sepsis has been investigated thoroughly and the result of these researches confirmed the high diagnostic accuracy of the PSP for sepsis. Of particular interest, PSP concentration has been shown to increase early in the development of a septic event, as illustrated in a cohort of severely burnt patients

Further reading

• De Reggi M, Gharib B (2002). "Protein-X, Pancreatic Stone-, Pancreatic thread-, reg-protein, P19, lithostathine, and now what? Characterization, structural analysis and putative function(s) of the major non-enzymatic protein of pancreatic secretions". Curr. Protein Pept. Sci. 2 (1): 19–42. doi:10.2174/1389203013381233. PMID 12369899.
• Itoh T, Tsuzuki H, Katoh T, Teraoka H, Matsumoto K, Yoshida N, Terazono K, Watanabe T, Yonekura H, Yamamoto H (1990). "Isolation and characterization of human reg protein produced in Saccharomyces cerevisiae". FEBS Lett. 272 (1–2): 85–8. doi:10.1016/0014-5793(90)80454-Q. PMID 2226837. S2CID 31078322.
• de la Monte SM, Ozturk M, Wands JR (1990). "Enhanced expression of an exocrine pancreatic protein in Alzheimer's disease and the developing human brain". J. Clin. Invest. 86 (3): 1004–13. doi:10.1172/JCI114762. PMC 296822. PMID 2394826.
• De Caro AM, Adrich Z, Fournet B, Capon C, Bonicel JJ, De Caro JD, Rovery M (1989). "N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the 5th amino acid residue". Biochim. Biophys. Acta. 994 (3): 281–4. doi:10.1016/0167-4838(89)90305-1. PMID 2493268.
• Giorgi D, Bernard JP, Rouquier S, Iovanna J, Sarles H, Dagorn JC (1989). "Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and expression in chronic calcifying pancreatitis". J. Clin. Invest. 84 (1): 100–6. doi:10.1172/JCI114128. PMC 303958. PMID 2525567.
• Stewart TA (1989). "The human reg gene encodes pancreatic stone protein". Biochem. J. 260 (2): 622–3. doi:10.1042/bj2600622. PMC 1138718. PMID 2764894.
• Terazono K, Yamamoto H, Takasawa S, Shiga K, Yonemura Y, Tochino Y, Okamoto H (1988). "A novel gene activated in regenerating islets". J. Biol. Chem. 263 (5): 2111–4. doi:10.1016/S0021-9258(18)69176-8. PMID 2963000.
• Rouimi P, Bonicel J, Rovery M, De Caro A (1987). "Cleavage of the Arg-Ile bond in the native polypeptide chain of human pancreatic stone protein". FEBS Lett. 216 (2): 195–9. doi:10.1016/0014-5793(87)80688-9. PMID 3108036. S2CID 37809879.
• Rouimi P, de Caro J, Bonicel J, Rovery M, de Caro A (1988). "The disulfide bridges of the immunoreactive forms of human pancreatic stone protein isolated from pancreatic juice". FEBS Lett. 229 (1): 171–4. doi:10.1016/0014-5793(88)80820-2. PMID 3345835. S2CID 24682537.
• Montalto G, Bonicel J, Multigner L, Rovery M, Sarles H, De Caro A (1987). "Partial amino acid sequence of human pancreatic stone protein, a novel pancreatic secretory protein". Biochem. J. 238 (1): 227–32. doi:10.1042/bj2380227. PMC 1147119. PMID 3541906.
• De Caro AM, Bonicel JJ, Rouimi P, De Caro JD, Sarles H, Rovery M (1987). "Complete amino acid sequence of an immunoreactive form of human pancreatic stone protein isolated from pancreatic juice". Eur. J. Biochem. 168 (1): 201–7. doi:10.1111/j.1432-1033.1987.tb13405.x. PMID 3665916.
• Gross J, Carlson RI, Brauer AW, Margolies MN, Warshaw AL, Wands JR (1986). "Isolation, characterization, and distribution of an unusual pancreatic human secretory protein". J. Clin. Invest. 76 (6): 2115–26. doi:10.1172/JCI112216. PMC 424321. PMID 3908481.
• Perfetti R, Hawkins AL, Griffin CA, Egan JM, Zenilman ME, Shuldiner AR (1994). "Assignment of the human pancreatic regenerating (REG) gene to chromosome 2p12". Genomics. 20 (2): 305–7. doi:10.1006/geno.1994.1173. PMID 8020983.
• Otonkoski T, Mally MI, Hayek A (1994). "Opposite effects of beta-cell differentiation and growth on reg expression in human fetal pancreatic cells". Diabetes. 43 (9): 1164–6. doi:10.2337/diabetes.43.9.1164. PMID 8070617.
• Moriizumi S, Watanabe T, Unno M, Nakagawara K, Suzuki Y, Miyashita H, Yonekura H, Okamoto H (1994). "Isolation, structural determination and expression of a novel reg gene, human regI beta". Biochim. Biophys. Acta. 1217 (2): 199–202. doi:10.1016/0167-4781(94)90035-3. PMID 8110835.
• Bartoli C, Gharib B, Giorgi D, Sansonetti A, Dagorn JC, Bergé-Lefranc JL (1993). "A gene homologous to the reg gene is expressed in the human pancreas". FEBS Lett. 327 (3): 289–93. doi:10.1016/0014-5793(93)81006-L. PMID 8348956. S2CID 44565895.
• Bertrand JA, Pignol D, Bernard JP, Verdier JM, Dagorn JC, Fontecilla-Camps JC (1996). "Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation". EMBO J. 15 (11): 2678–84. doi:10.1002/j.1460-2075.1996.tb00628.x. PMC 450203. PMID 8654365.
• Patard L, Stoven V, Gharib B, Bontems F, Lallemand JY, De Reggi M (1997). "What function for human lithostathine?: structural investigations by three-dimensional structure modeling and high-resolution NMR spectroscopy". Protein Eng. 9 (11): 949–57. doi:10.1093/protein/9.11.949. PMID 8961348.