ID   PRB4_HUMAN              Reviewed;         310 AA.
AC   P10163; A1L439; O00600; P02813; P10161; P10162; P81489;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   14-MAY-2014, sequence version 4.
DT   08-NOV-2023, entry version 147.
DE   RecName: Full=Basic salivary proline-rich protein 4;
DE            Short=Salivary proline-rich protein Po;
DE   AltName: Full=Parotid o protein;
DE   AltName: Full=Salivary proline-rich protein II-1;
DE   Contains:
DE     RecName: Full=Protein N1;
DE   Contains:
DE     RecName: Full=Glycosylated protein A;
DE   Contains:
DE     RecName: Full=Peptide P-D;
DE     AltName: Full=Proline-rich peptide IB-5;
DE   Flags: Precursor;
GN   Name=PRB4;
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] (ALLELE S), AND POLYMORPHISM.
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 L AND S), AND POLYMORPHISM.
RX   PubMed=2851479; DOI=10.1093/genetics/120.1.267;
RA   Lyons K.M., Stein J.H., Smithies O.;
RT   "Length polymorphisms in human proline-rich protein genes generated by
RT   intragenic unequal crossing over.";
RL   Genetics 120:267-278(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA   Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA   Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA   Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA   Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA   Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA   Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA   Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA   Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA   Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA   Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA   Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA   Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA   David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA   D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA   Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA   Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA   Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA   LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA   Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA   Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA   Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA   Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA   Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA   Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA   Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA   Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA   Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA   Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA   Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ALLELE M), AND VARIANT PRO-272.
RC   TISSUE=Cerebellum;
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   [5]
RP   PROTEIN SEQUENCE OF 17-112 AND 155-240.
RC   TISSUE=Saliva;
RX   PubMed=8373986; DOI=10.1177/10454411930040030501;
RA   Kauffman D.L., Keller P.J., Bennick A., Blum M.;
RT   "Alignment of amino acid and DNA sequences of human proline-rich
RT   proteins.";
RL   Crit. Rev. Oral Biol. Med. 4:287-292(1993).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 31-310 (ALLELE M), AND VARIANT
RP   PRO-272.
RX   PubMed=8554050;
RA   Azen E.A., Amberger E., Fisher S., Prakobphol A., Niece R.L.;
RT   "PRB1, PRB2, and PRB4 coded polymorphisms among human salivary
RT   concanavalin-A binding, II-1, and Po proline-rich proteins.";
RL   Am. J. Hum. Genet. 58:143-153(1996).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-310, AND VARIANT PRO-272.
RX   PubMed=3220251; DOI=10.1093/genetics/120.1.255;
RA   Lyons K.M., Stein J.H., Smithies O.;
RT   "Many protein products from a few loci: assignment of human salivary
RT   proline-rich proteins to specific loci.";
RL   Genetics 120:255-265(1988).
RN   [8]
RP   PROTEIN SEQUENCE OF 241-310.
RC   TISSUE=Saliva;
RX   PubMed=6841349; DOI=10.1093/oxfordjournals.jbchem.a134204;
RA   Saitoh E., Isemura S., Sanada K.;
RT   "Complete amino acid sequence of a basic proline-rich peptide, P-D, from
RT   human parotid saliva.";
RL   J. Biochem. 93:495-502(1983).
RN   [9]
RP   PROTEIN SEQUENCE OF 241-310.
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   [10]
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   [11]
RP   GLYCOSYLATION AT ASN-87, PYROGLUTAMATE FORMATION, VARIANTS ALLELE L AND M,
RP   AND IDENTIFICATION BY 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).
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20879038}.
CC   -!- PTM: Proteolytically cleaved at the tripeptide Xaa-Pro-Gln, where Xaa
CC       in the P(3) position is mostly lysine. The endoprotease may be of
CC       microbial origin. Pyroglutamate formation found on at least Gln-46,
CC       Gln-48, Gln-67, Gln-88; Gln-90; Gln-193; Gln-288 Gln-214 and Gln-295,
CC       preferentially in diabetic, and head and neck cancer patients.
CC       {ECO:0000269|PubMed:18463091}.
CC   -!- POLYMORPHISM: The number of repeats is polymorphic and varies among
CC       different alleles. Allele S (short), allele M (medium) and allele L
CC       (long) contain 6, 7 and 9 tandem repeats respectively.
CC       {ECO:0000269|PubMed:2851479}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA30543.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAA30729.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; K03207; AAA60188.1; -; mRNA.
DR   EMBL; X07882; CAA30729.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; X07715; CAA30543.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AC010176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC130386; AAI30387.1; -; mRNA.
DR   EMBL; S80916; AAB50687.2; -; Genomic_DNA.
DR   EMBL; X07704; CAA30542.1; -; Genomic_DNA.
DR   PIR; S03176; PIHUSD.
DR   AlphaFoldDB; P10163; -.
DR   BioGRID; 111536; 3.
DR   STRING; 9606.ENSP00000279575; -.
DR   GlyCosmos; P10163; 8 sites, No reported glycans.
DR   GlyGen; P10163; 8 sites.
DR   iPTMnet; P10163; -.
DR   BioMuta; PRB4; -.
DR   DMDM; 158517854; -.
DR   MassIVE; P10163; -.
DR   PaxDb; 9606-ENSP00000279575; -.
DR   PeptideAtlas; P10163; -.
DR   Pumba; P10163; -.
DR   TopDownProteomics; P10163; -.
DR   AGR; HGNC:9340; -.
DR   GeneCards; PRB4; -.
DR   HGNC; HGNC:9340; PRB4.
DR   MIM; 180990; gene.
DR   neXtProt; NX_P10163; -.
DR   PharmGKB; PA33702; -.
DR   eggNOG; ENOG502RU4G; Eukaryota.
DR   InParanoid; P10163; -.
DR   PathwayCommons; P10163; -.
DR   SIGNOR; P10163; -.
DR   GeneWiki; PRB4; -.
DR   Pharos; P10163; Tdark.
DR   PRO; PR:P10163; -.
DR   Proteomes; UP000005640; Unplaced.
DR   RNAct; P10163; Protein.
DR   GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR   DisProt; DP00119; -.
DR   InterPro; IPR026086; Pro-rich.
DR   PANTHER; PTHR23203:SF15; BASIC SALIVARY PROLINE-RICH PROTEIN 4; 1.
DR   PANTHER; PTHR23203; PROLINE-RICH PROTEIN; 1.
DR   Pfam; PF15240; Pro-rich; 2.
DR   SMART; SM01412; Pro-rich; 2.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Glycoprotein; Pyrrolidone carboxylic acid;
KW   Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL          1..16
FT                   /evidence="ECO:0000269|PubMed:8373986"
FT   CHAIN           17..310
FT                   /note="Basic salivary proline-rich protein 4"
FT                   /id="PRO_0000022102"
FT   PEPTIDE         17..39
FT                   /note="Protein N1"
FT                   /id="PRO_0000022103"
FT   CHAIN           40..177
FT                   /note="Glycosylated protein A"
FT                   /id="PRO_0000022104"
FT   CHAIN           241..310
FT                   /note="Peptide P-D"
FT                   /id="PRO_0000022099"
FT   REPEAT          35..55
FT                   /note="1"
FT   REPEAT          56..76
FT                   /note="2"
FT   REPEAT          77..97
FT                   /note="3"
FT   REPEAT          98..118
FT                   /note="4"
FT   REPEAT          119..139
FT                   /note="5"
FT   REPEAT          140..160
FT                   /note="6"
FT   REPEAT          161..181
FT                   /note="7"
FT   REPEAT          182..202
FT                   /note="8"
FT   REPEAT          203..223
FT                   /note="9"
FT   REPEAT          224..234
FT                   /note="10; truncated"
FT   REGION          14..310
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          35..234
FT                   /note="9.5 X 21 AA tandem repeats of K-P-[EQ]-[GR]-[PR]-
FT                   [PR]-P-Q-G-G-N-Q-[PS]-[QH]-[RG]-[PT]-P-P-[PH]-P-G"
FT   COMPBIAS        45..122
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        129..229
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        243..310
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        66
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:20879038"
FT   CARBOHYD        108
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        150
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        171
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        213
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         113..154
FT                   /note="Missing (in allele M and allele S)"
FT                   /id="VAR_035034"
FT   VARIANT         164..184
FT                   /note="Missing (in allele S)"
FT                   /id="VAR_035035"
FT   VARIANT         185
FT                   /note="R -> G (in dbSNP:rs11054244)"
FT                   /id="VAR_031548"
FT   VARIANT         186
FT                   /note="P -> R (in dbSNP:rs11054243)"
FT                   /id="VAR_031549"
FT   VARIANT         200
FT                   /note="P -> H (in dbSNP:rs12308244)"
FT                   /id="VAR_031550"
FT   VARIANT         272
FT                   /note="A -> P (in dbSNP:rs1052808)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:3220251, ECO:0000269|PubMed:8554050"
FT                   /id="VAR_031551"
FT   CONFLICT        28
FT                   /note="S -> P (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        31..39
FT                   /note="LISGKPEGR -> IIPPKPPG (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        31..33
FT                   /note="LIS -> PPP (in Ref. 6; AAB50687)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        37
FT                   /note="E -> Q (in Ref. 2; CAA30543 and 7; CAA30542)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        66
FT                   /note="N -> D (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        74..94
FT                   /note="Missing (in Ref. 7; CAA30542)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        96
FT                   /note="P -> PP (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        101
FT                   /note="R -> E (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        122..123
FT                   /note="SR -> RP (in Ref. 7; CAA30542)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        129
FT                   /note="H -> N (in Ref. 7; CAA30542)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        154..174
FT                   /note="Missing (in Ref. 7; CAA30542)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        169..171
FT                   /note="GGN -> QGG (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        192
FT                   /note="N -> D (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        213
FT                   /note="N -> D (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   310 AA;  31326 MW;  079538A1BC412D0F CRC64;
     MLLILLSVAL LALSSAESSS EDVSQEESLF LISGKPEGRR PQGGNQPQRP PPPPGKPQGP
     PPQGGNQSQG PPPPPGKPEG RPPQGGNQSQ GPPPHPGKPE RPPPQGGNQS QGPPPHPGKP
     ESRPPQGGHQ SQGPPPTPGK PEGPPPQGGN QSQGTPPPPG KPEGRPPQGG NQSQGPPPHP
     GKPERPPPQG GNQSHRPPPP PGKPERPPPQ GGNQSQGPPP HPGKPEGPPP QEGNKSRSAR
     SPPGKPQGPP QQEGNKPQGP PPPGKPQGPP PAGGNPQQPQ APPAGKPQGP PPPPQGGRPP
     RPAQGQQPPQ
//