PROL1_HUMAN
ID PROL1_HUMAN Reviewed; 248 AA.
AC Q99935; A8MZ07; P85047;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 02-MAR-2010, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Opiorphin prepropeptide {ECO:0000312|HGNC:HGNC:17279};
DE AltName: Full=Basic proline-rich lacrimal protein;
DE AltName: Full=Proline-rich protein 1;
DE Short=PRL1;
DE Contains:
DE RecName: Full=Opiorphin;
DE Flags: Precursor;
GN Name=OPRPN {ECO:0000312|HGNC:HGNC:17279}; Synonyms=BPLP, PROL1;
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].
RC TISSUE=Lacrimal gland;
RX PubMed=8670737; DOI=10.3109/02713689608995828;
RA Dickinson D.P., Thiesse M.;
RT "cDNA cloning of an abundant human lacrimal gland mRNA encoding a novel
RT tear protein.";
RL Curr. Eye Res. 15:377-386(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [4]
RP PROTEIN SEQUENCE OF 22-43, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP PYROGLUTAMATE FORMATION AT GLN-22.
RC TISSUE=Tear;
RX PubMed=25946035; DOI=10.1021/acs.jproteome.5b00179;
RA Azkargorta M., Soria J., Ojeda C., Guzman F., Acera A., Iloro I.,
RA Suarez T., Elortza F.;
RT "Human basal tear peptidome characterization by CID, HCD, and ETD followed
RT by in silico and in vitro analyses for antimicrobial peptide
RT identification.";
RL J. Proteome Res. 14:2649-2658(2015).
RN [5]
RP PROTEIN SEQUENCE OF 22-26, FUNCTION, SUBCELLULAR LOCATION, PYROGLUTAMATE
RP FORMATION AT GLN-22, AND MASS SPECTROMETRY.
RC TISSUE=Saliva;
RX PubMed=17101991; DOI=10.1073/pnas.0605865103;
RA Wisner A., Dufour E., Messaoudi M., Nejdi A., Marcel A., Ungeheuer M.-N.,
RA Rougeot C.;
RT "Human opiorphin, a natural antinociceptive modulator of opioid-dependent
RT pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:17979-17984(2006).
CC -!- FUNCTION: Opiorphin is an endogenous inhibitor of neprilysin and
CC aminopeptidase N. Inhibits the breakdown of substance P, Mca-BK2 and
CC Met-enkephalin by neprilysin in vitro with IC(50) values of 29 uM, 33
CC uM and 33 uM respectively. Inhibits the breakdown of Ala-pNA by
CC aminopeptidase N in vitro with an IC(50) of 65 uM. Has a potent
CC analgesic effect when administered to rats by intravenous injection.
CC {ECO:0000269|PubMed:17101991}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17101991}.
CC -!- TISSUE SPECIFICITY: Abundantly expressed in lacrimal gland where it
CC found in the secretory endpieces. Also expressed at modest levels in
CC the submandibular gland.
CC -!- MASS SPECTROMETRY: [Opiorphin]: Mass=690; Method=SELDI;
CC Evidence={ECO:0000269|PubMed:17101991};
CC -!- SIMILARITY: Belongs to the PROL1/PROL3 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB46823.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; S83198; AAB46823.1; ALT_FRAME; mRNA.
DR EMBL; AC106884; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471057; EAX05620.1; -; Genomic_DNA.
DR CCDS; CCDS43235.1; -.
DR RefSeq; NP_067048.4; NM_021225.4.
DR AlphaFoldDB; Q99935; -.
DR BioGRID; 121831; 11.
DR IntAct; Q99935; 1.
DR STRING; 9606.ENSP00000382485; -.
DR GlyGen; Q99935; 1 site.
DR BioMuta; OPRPN; -.
DR DMDM; 290457653; -.
DR MassIVE; Q99935; -.
DR PaxDb; Q99935; -.
DR PeptideAtlas; Q99935; -.
DR PRIDE; Q99935; -.
DR ProteomicsDB; 78530; -.
DR Antibodypedia; 24327; 31 antibodies from 11 providers.
DR DNASU; 58503; -.
DR Ensembl; ENST00000399575.7; ENSP00000382485.2; ENSG00000171199.11.
DR GeneID; 58503; -.
DR KEGG; hsa:58503; -.
DR MANE-Select; ENST00000399575.7; ENSP00000382485.2; NM_021225.5; NP_067048.4.
DR UCSC; uc003hfi.4; human.
DR CTD; 58503; -.
DR DisGeNET; 58503; -.
DR GeneCards; OPRPN; -.
DR HGNC; HGNC:17279; OPRPN.
DR HPA; ENSG00000171199; Tissue enriched (salivary).
DR MIM; 608936; gene.
DR neXtProt; NX_Q99935; -.
DR OpenTargets; ENSG00000171199; -.
DR PharmGKB; PA33803; -.
DR VEuPathDB; HostDB:ENSG00000171199; -.
DR eggNOG; ENOG502RWXN; Eukaryota.
DR GeneTree; ENSGT00730000111944; -.
DR HOGENOM; CLU_1124221_0_0_1; -.
DR InParanoid; Q99935; -.
DR OMA; PFYLAIY; -.
DR OrthoDB; 1458751at2759; -.
DR PhylomeDB; Q99935; -.
DR TreeFam; TF342130; -.
DR PathwayCommons; Q99935; -.
DR SignaLink; Q99935; -.
DR BioGRID-ORCS; 58503; 13 hits in 1062 CRISPR screens.
DR GenomeRNAi; 58503; -.
DR Pharos; Q99935; Tdark.
DR PRO; PR:Q99935; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q99935; protein.
DR Bgee; ENSG00000171199; Expressed in buccal mucosa cell and 43 other tissues.
DR Genevisible; Q99935; HS.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IDA:UniProtKB.
DR GO; GO:0001895; P:retina homeostasis; HEP:UniProtKB.
DR InterPro; IPR026288; SMR-like.
DR PANTHER; PTHR14179; PTHR14179; 1.
DR Pfam; PF15621; PROL5-SMR; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Glycoprotein; Protease inhibitor;
KW Pyrrolidone carboxylic acid; Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000269|PubMed:17101991,
FT ECO:0000269|PubMed:25946035"
FT CHAIN 22..248
FT /note="Opiorphin prepropeptide"
FT /id="PRO_0000022111"
FT PEPTIDE 22..26
FT /note="Opiorphin"
FT /id="PRO_0000271169"
FT REGION 150..198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 22
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:17101991,
FT ECO:0000269|PubMed:25946035"
FT CARBOHYD 218
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 166
FT /note="S -> G (in Ref. 1; AAB46823)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 248 AA; 27217 MW; DB3EF5A6F25C02D5 CRC64;
MKLTFFLGLL ALISCFTPSE SQRFSRRPYL PGQLPPPPLY RPRWVPPSPP PPYDSRLNSP
LSLPFVPGRV PPSSFSRFSQ AVILSQLFPL ESIRQPRLFP GYPNLHFPLR PYYVGPIRIL
KPPFPPIPFF LAIYLPISNP EPQINITTAD TTITTNPPTT ATATTSTSTK PTMTISSSTV
PISSTPEPAT SISAATPAAS TENTTQILAN RPHTVLLNAT VQVTTSNQTI LSSPAFKSFW
QKLFAIFG
