PRPC_HUMAN
ID PRPC_HUMAN Reviewed; 166 AA.
AC P02810; A2VCM0; A3KN66; A5D902; B2RMW2; Q4VBP2; Q53XA2; Q6P2F6;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Salivary acidic proline-rich phosphoprotein 1/2;
DE AltName: Full=Db-s;
DE AltName: Full=PRP-1/PRP-2;
DE AltName: Full=Parotid acidic protein;
DE Short=Pa;
DE AltName: Full=Parotid double-band protein;
DE AltName: Full=Parotid isoelectric focusing variant protein;
DE Short=PIF-S;
DE AltName: Full=Parotid proline-rich protein 1/2;
DE AltName: Full=Pr1/Pr2;
DE AltName: Full=Protein C;
DE Contains:
DE RecName: Full=Salivary acidic proline-rich phosphoprotein 1/2;
DE Contains:
DE RecName: Full=Salivary acidic proline-rich phosphoprotein 3/4;
DE AltName: Full=Db-F;
DE AltName: Full=PIF-F;
DE AltName: Full=PRP-3/PRP-4;
DE AltName: Full=Protein A;
DE Contains:
DE RecName: Full=Peptide P-C;
DE Flags: Precursor;
GN Name=PRH1;
GN and
GN Name=PRH2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELES PRH1-PIF AND PRH2-1).
RX PubMed=2993301; DOI=10.1016/s0021-9258(17)39156-1;
RA Maeda N., Kim H.-S., Azen E.A., Smithies O.;
RT "Differential RNA splicing and post-translational cleavages in the human
RT salivary proline-rich protein gene system.";
RL J. Biol. Chem. 260:11123-11130(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES PRH1-PIF AND PRH2-1).
RX PubMed=3009472; DOI=10.1016/s0021-9258(19)62674-8;
RA Kim H.-S., Maeda N.;
RT "Structures of two HaeIII-type genes in the human salivary proline-rich
RT protein multigene family.";
RL J. Biol. Chem. 261:6712-6718(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE PRH2-1).
RC TISSUE=Salivary gland;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELE PRH1-PIF), AND
RP VARIANT ASN-66.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELES PRH1-DB; PRH1-PIF; PRH2-1
RP AND PRH2-2).
RC TISSUE=Thyroid;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 17-166 (PROTEIN C).
RC TISSUE=Saliva;
RX PubMed=7380845; DOI=10.1016/s0021-9258(19)70721-2;
RA Wong R.S.C., Bennick A.;
RT "The primary structure of a salivary calcium-binding proline-rich
RT phosphoprotein (protein C), a possible precursor of a related salivary
RT protein A.";
RL J. Biol. Chem. 255:5943-5948(1980).
RN [7]
RP PROTEIN SEQUENCE OF 17-166 (PRP-2).
RC TISSUE=Saliva;
RX PubMed=3710693; DOI=10.1111/j.1399-3011.1986.tb01030.x;
RA Schlesinger D.H., Hay D.I.;
RT "Complete covalent structure of a proline-rich phosphoprotein, PRP-2, an
RT inhibitor of calcium phosphate crystal growth from human parotid saliva.";
RL Int. J. Pept. Protein Res. 27:373-379(1986).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 17-166 (ALLELES PRH1-PIF; PRH1-PA AND
RP PRH1-DB).
RX PubMed=3687941;
RA Azen E.A., Kim H.S., Goodman P., Flynn S., Maeda N.;
RT "Alleles at the PRH1 locus coding for the human salivary-acidic proline-
RT rich proteins Pa, Db, and PIF.";
RL Am. J. Hum. Genet. 41:1035-1047(1987).
RN [9]
RP PROTEIN SEQUENCE OF 17-166 (PRP-1 TO PRP-4; PIF-F AND PIF-S), AND
RP PYROGLUTAMATE FORMATION AT GLN-17.
RC TISSUE=Saliva;
RX PubMed=3196309; DOI=10.1042/bj2550015;
RA Hay D.I., Bennick A., Schlesinger D.H., Minaguchi K., Madapallimattam G.,
RA Schluckebier S.K.;
RT "The primary structures of six human salivary acidic proline-rich proteins
RT (PRP-1, PRP-2, PRP-3, PRP-4, PIF-s and PIF-f).";
RL Biochem. J. 255:15-21(1988).
RN [10]
RP PROTEIN SEQUENCE OF 17-122 (PROTEIN A).
RC TISSUE=Saliva;
RX PubMed=438215; DOI=10.1016/s0021-9258(17)30083-2;
RA Wong R.S.C., Hofmann T., Bennick A.;
RT "The complete primary structure of a proline-rich phosphoprotein from human
RT saliva.";
RL J. Biol. Chem. 254:4800-4808(1979).
RN [11]
RP PROTEIN SEQUENCE OF 17-122 (PROTEIN A).
RA Schlesinger D.H., Hay D.I.;
RT "Complete primary structure of a proline-rich phosphoprotein (PRP-4), a
RT potent inhibitor of calcium phosphate precipitation in human parotid
RT saliva.";
RL (In) Gross E., Meienhofer J. (eds.);
RL Peptides: structure and biological function (Proceedings of the 6th
RL American peptide symposium), pp.133-136, Pierce Chemical Co., Rockford Il.
RL (1979).
RN [12]
RP PROTEIN SEQUENCE OF 17-46 (PROTEIN C).
RC TISSUE=Saliva;
RX PubMed=7228490; DOI=10.1111/j.1399-3011.1981.tb01965.x;
RA Schlesinger D.H., Hay D.I.;
RT "Primary structure of the active tryptic fragments of human and monkey
RT salivary anionic proline-rich proteins.";
RL Int. J. Pept. Protein Res. 17:34-41(1981).
RN [13]
RP PROTEIN SEQUENCE OF 17-46 (PROTEIN DB-S), PROTEIN SEQUENCE OF 91-97
RP (PROTEIN DB-S), IDENTIFICATION BY MASS SPECTROMETRY OF PIF-S; PIF-F; DB-S;
RP DB-F; PA; PRP-1 TO PRP4 AND PEPTIDE P-C, AND PHOSPHORYLATION AT SER-24;
RP SER-33 AND SER-38.
RC TISSUE=Saliva;
RX PubMed=15693058; DOI=10.1002/pmic.200401156;
RA Inzitari R., Cabras T., Onnis G., Olmi C., Mastinu A., Sanna M.T.,
RA Pellegrini M.G., Castagnola M., Messana I.;
RT "Different isoforms and post-translational modifications of human salivary
RT acidic proline-rich proteins.";
RL Proteomics 5:805-815(2005).
RN [14]
RP PROTEIN SEQUENCE OF 123-166 (PEPTIDE P-C).
RC TISSUE=Saliva;
RX PubMed=7390979;
RA Isemura S., Saitoh E., Sanada K.;
RT "The amino acid sequence of a salivary proline-rich peptide, P-C, and its
RT relation to a salivary proline-rich phosphoprotein, protein C.";
RL J. Biochem. 87:1071-1077(1980).
RN [15]
RP PROTEIN SEQUENCE OF 123-166.
RC TISSUE=Saliva;
RX PubMed=1849422; DOI=10.1021/bi00228a001;
RA Kauffman D.L., Bennick A., Blum M., Keller P.J.;
RT "Basic proline-rich proteins from human parotid saliva: relationships of
RT the covalent structures of ten proteins from a single individual.";
RL Biochemistry 30:3351-3356(1991).
RN [16]
RP GLYCOSYLATION AT SER-33, PHOSPHORYLATION AT SER-24 AND SER-38, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=10858503; DOI=10.1016/s0014-5793(00)01645-8;
RA Jonsson A.P., Griffiths W.J., Bratt P., Johansson I., Stroemberg N.,
RA Joernvall H., Bergman T.;
RT "A novel Ser O-glucuronidation in acidic proline-rich proteins identified
RT by tandem mass spectrometry.";
RL FEBS Lett. 475:131-134(2000).
RN [17]
RP PROTEOLYTIC PROCESSING, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18463091; DOI=10.1074/jbc.m708282200;
RA Helmerhorst E.J., Sun X., Salih E., Oppenheim F.G.;
RT "Identification of Lys-Pro-Gln as a novel cleavage site specificity of
RT saliva-associated proteases.";
RL J. Biol. Chem. 283:19957-19966(2008).
RN [18]
RP GLYCOSYLATION AT SER-38, PHOSPHORYLATION AT SER-38, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=20879038; DOI=10.1002/pmic.201000261;
RA Vitorino R., Alves R., Barros A., Caseiro A., Ferreira R., Lobo M.C.,
RA Bastos A., Duarte J., Carvalho D., Santos L.L., Amado F.L.;
RT "Finding new posttranslational modifications in salivary proline-rich
RT proteins.";
RL Proteomics 10:3732-3742(2010).
RN [19]
RP PHOSPHORYLATION AT SER-24 AND SER-38, AND MUTAGENESIS OF SER-24 AND SER-38.
RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028;
RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J.,
RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N.,
RA Pinna L.A., Pagliarini D.J., Dixon J.E.;
RT "A single kinase generates the majority of the secreted phosphoproteome.";
RL Cell 161:1619-1632(2015).
RN [20]
RP VARIANT PRH2-3 LYS-163.
RX PubMed=10627138;
RX DOI=10.1002/(sici)1098-1004(1998)12:1<72::aid-humu18>3.0.co;2-w;
RA Azen E.A.;
RT "A frequent mutation in the acidic proline-rich protein gene, PRH2, causing
RT a Q147K change closely adjacent to the bacterial binding domain of the
RT cognate salivary PRP (Pr1') in Afro-Americans.";
RL Hum. Mutat. 12:72-72(1998).
CC -!- FUNCTION: PRP's act as highly potent inhibitors of crystal growth of
CC calcium phosphates. They provide a protective and reparative
CC environment for dental enamel which is important for the integrity of
CC the teeth.
CC -!- INTERACTION:
CC P02810; Q8IXL6: FAM20C; NbExp=2; IntAct=EBI-738601, EBI-7147442;
CC P02810; Q8TAX7: MUC7; NbExp=2; IntAct=EBI-738601, EBI-738582;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: Proteolytically cleaved; PRP-2, PRP-1, PIF-S and Db-S yield PRP-4,
CC PRP-3 (protein A), PIF-F and Db-F, respectively.
CC {ECO:0000269|PubMed:18463091}.
CC -!- PTM: An hexuronic acid was shown to be linked to Ser-33 in about 40% of
CC the polypeptides. Neither the structure of the carbohydrate (whether
CC glucuronic acid or an isomer of), nor the linkage (whether a glycoside
CC or an ester) has been definitely established.
CC {ECO:0000269|PubMed:10858503}.
CC -!- POLYMORPHISM: Sequence shown is that of allele PRH2-2, also known as
CC PR-2; Allele PRH2-1 is also known as PR-1 or protein C, and allele
CC PRH2-3 as PR-1'. The PRH1-DB allele (about 16% of the population) has
CC an insertion of 21 repeated amino acids compared to the more frequent
CC PRH1-PIF allele (68%). In contrast to all other PRH1 and PRH2 alleles,
CC the PRH1-PA allele (16%) is not proteolytically cleaved.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI28193.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI41917.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
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DR EMBL; K03202; AAA60183.1; -; mRNA.
DR EMBL; K03203; AAA60184.1; -; mRNA.
DR EMBL; M13057; AAA98807.1; -; Genomic_DNA.
DR EMBL; M13058; AAA98808.1; -; Genomic_DNA.
DR EMBL; BX641094; CAE46044.1; -; mRNA.
DR EMBL; CH471094; EAW96214.1; -; Genomic_DNA.
DR EMBL; CH471094; EAW96219.1; -; Genomic_DNA.
DR EMBL; BC095488; AAH95488.1; -; mRNA.
DR EMBL; BC128192; AAI28193.1; ALT_SEQ; mRNA.
DR EMBL; BC133676; AAI33677.1; -; mRNA.
DR EMBL; BC136499; AAI36500.1; -; mRNA.
DR EMBL; BC141916; AAI41917.1; ALT_SEQ; mRNA.
DR CCDS; CCDS8636.1; -.
DR PIR; A25372; PIHUSC.
DR PIR; B25372; B25372.
DR RefSeq; NP_001103683.1; NM_001110213.1.
DR RefSeq; NP_001278243.1; NM_001291314.1.
DR RefSeq; NP_001278244.1; NM_001291315.1.
DR AlphaFoldDB; P02810; -.
DR BioGRID; 111545; 17.
DR BioGRID; 111546; 1.
DR IntAct; P02810; 7.
DR MINT; P02810; -.
DR STRING; 9606.ENSP00000379682; -.
DR GlyGen; P02810; 2 sites.
DR iPTMnet; P02810; -.
DR PhosphoSitePlus; P02810; -.
DR BioMuta; PRH1; -.
DR DMDM; 131008; -.
DR jPOST; P02810; -.
DR MassIVE; P02810; -.
DR MaxQB; P02810; -.
DR PaxDb; P02810; -.
DR PeptideAtlas; P02810; -.
DR PRIDE; P02810; -.
DR ProteomicsDB; 51603; -.
DR TopDownProteomics; P02810; -.
DR Antibodypedia; 67598; 70 antibodies from 11 providers.
DR DNASU; 5554; -.
DR Ensembl; ENST00000381847.7; ENSP00000371271.3; ENSG00000134551.13.
DR Ensembl; ENST00000396400.4; ENSP00000379682.3; ENSG00000134551.13.
DR Ensembl; ENST00000572141.1; ENSP00000458690.1; ENSG00000272803.5.
DR Ensembl; ENST00000575657.5; ENSP00000461041.1; ENSG00000272803.5.
DR Ensembl; ENST00000622570.4; ENSP00000481810.1; ENSG00000275679.4.
DR Ensembl; ENST00000622848.2; ENSP00000483458.1; ENSG00000275679.4.
DR GeneID; 5554; -.
DR GeneID; 5555; -.
DR KEGG; hsa:5554; -.
DR KEGG; hsa:5555; -.
DR UCSC; uc001qzi.5; human.
DR CTD; 5554; -.
DR CTD; 5555; -.
DR DisGeNET; 5554; -.
DR DisGeNET; 5555; -.
DR GeneCards; PRH1; -.
DR GeneCards; PRH2; -.
DR HGNC; HGNC:9366; PRH1.
DR HGNC; HGNC:9367; PRH2.
DR HPA; ENSG00000134551; Tissue enriched (salivary).
DR MIM; 168730; gene.
DR MIM; 168790; gene.
DR neXtProt; NX_P02810; -.
DR PharmGKB; PA33738; -.
DR VEuPathDB; HostDB:ENSG00000134551; -.
DR eggNOG; ENOG502TED6; Eukaryota.
DR HOGENOM; CLU_054768_2_0_1; -.
DR InParanoid; P02810; -.
DR OrthoDB; 1645809at2759; -.
DR PathwayCommons; P02810; -.
DR SignaLink; P02810; -.
DR SIGNOR; P02810; -.
DR BioGRID-ORCS; 5554; 13 hits in 234 CRISPR screens.
DR BioGRID-ORCS; 5555; 14 hits in 1025 CRISPR screens.
DR GeneWiki; PRH1; -.
DR Pharos; P02810; Tbio.
DR PRO; PR:P02810; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P02810; protein.
DR Bgee; ENSG00000134551; Expressed in olfactory segment of nasal mucosa and 101 other tissues.
DR Genevisible; P02810; HS.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR InterPro; IPR026086; Pro-rich.
DR PANTHER; PTHR23203; PTHR23203; 2.
DR Pfam; PF15240; Pro-rich; 1.
DR SMART; SM01412; Pro-rich; 1.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Glycoprotein; Phosphoprotein; Pyrrolidone carboxylic acid;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:15693058,
FT ECO:0000269|PubMed:3196309, ECO:0000269|PubMed:3710693,
FT ECO:0000269|PubMed:438215, ECO:0000269|PubMed:7228490,
FT ECO:0000269|PubMed:7380845, ECO:0000269|Ref.11"
FT CHAIN 17..166
FT /note="Salivary acidic proline-rich phosphoprotein 1/2"
FT /id="PRO_0000022137"
FT CHAIN 17..122
FT /note="Salivary acidic proline-rich phosphoprotein 3/4"
FT /id="PRO_0000022138"
FT CHAIN 123..166
FT /note="Peptide P-C"
FT /id="PRO_0000022139"
FT REGION 16..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 17..46
FT /note="Inhibits hydroxyapatite formation, binds to
FT hydroxyapatite and calcium"
FT COMPBIAS 50..78
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 79..166
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 17
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:3196309"
FT MOD_RES 24
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:10858503,
FT ECO:0000269|PubMed:15693058, ECO:0000269|PubMed:26091039"
FT MOD_RES 33
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000269|PubMed:15693058"
FT MOD_RES 38
FT /note="Phosphoserine; by FAM20C; alternate"
FT /evidence="ECO:0000269|PubMed:10858503,
FT ECO:0000269|PubMed:15693058, ECO:0000269|PubMed:20879038,
FT ECO:0000269|PubMed:26091039"
FT CARBOHYD 33
FT /note="O-linked (GlcA) serine; alternate"
FT /evidence="ECO:0000269|PubMed:10858503"
FT CARBOHYD 38
FT /note="O-linked (GlcA) serine; alternate"
FT /evidence="ECO:0000269|PubMed:20879038"
FT VARIANT 20
FT /note="D -> N (in allele PRH1-PIF, allele PRH1-PA and
FT allele PRH1-DB; dbSNP:rs1130404)"
FT /id="VAR_005563"
FT VARIANT 42
FT /note="I -> L (in allele PRH1-PA and allele PRH1-DB;
FT dbSNP:rs2923234)"
FT /id="VAR_023240"
FT VARIANT 66
FT /note="D -> N (in allele PRH2-1; dbSNP:rs1049112)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_005564"
FT VARIANT 97
FT /note="Q -> QGGQQQQGPPPPQGKPQGPPQQ (in allele PRH1-DB)"
FT /id="VAR_023241"
FT VARIANT 119
FT /note="R -> C (in allele PRH1-PA; interferes with
FT proteolytic cleavage at Arg-122; dbSNP:rs200488155)"
FT /id="VAR_023242"
FT VARIANT 163
FT /note="Q -> K (in allele PRH2-3; dbSNP:rs74062407)"
FT /evidence="ECO:0000269|PubMed:10627138"
FT /id="VAR_005565"
FT MUTAGEN 24
FT /note="S->A: Decreased phosphorylation by FAM20C; when
FT associated with A-38."
FT /evidence="ECO:0000269|PubMed:26091039"
FT MUTAGEN 38
FT /note="S->A: Decreased phosphorylation by FAM20C; when
FT associated with A-24."
FT /evidence="ECO:0000269|PubMed:26091039"
FT CONFLICT 41
FT /note="F -> P (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 166 AA; 17016 MW; A7DF62BF94E3C3EF CRC64;
MLLILLSVAL LAFSSAQDLD EDVSQEDVPL VISDGGDSEQ FIDEERQGPP LGGQQSQPSA
GDGNQDDGPQ QGPPQQGGQQ QQGPPPPQGK PQGPPQQGGH PPPPQGRPQG PPQQGGHPRP
PRGRPQGPPQ QGGHQQGPPP PPPGKPQGPP PQGGRPQGPP QGQSPQ
