PNOC_HUMAN
ID PNOC_HUMAN Reviewed; 176 AA.
AC Q13519; B7Z749; Q6FH16;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Prepronociceptin;
DE Contains:
DE RecName: Full=Nocistatin;
DE Contains:
DE RecName: Full=Nociceptin;
DE AltName: Full=Orphanin FQ;
DE AltName: Full=PPNOC;
DE Contains:
DE RecName: Full=Orphanin FQ2;
DE Flags: Precursor;
GN Name=PNOC; Synonyms=OFQ;
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=8710928; DOI=10.1073/pnas.93.16.8666;
RA Mollereau C., Simons M.-J., Soularue P., Liners F., Vassart G.,
RA Meunier J.-C., Parmentier M.;
RT "Structure, tissue distribution, and chromosomal localization of the
RT prepronociceptin gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:8666-8670(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8710930; DOI=10.1073/pnas.93.16.8677;
RA Nothacker H.-P., Reinscheid R.K., Mansour A., Henningsen R.A., Ardati A.,
RA Monsma F.J. Jr., Watson S.J., Civelli O.;
RT "Primary structure and tissue distribution of the orphanin FQ precursor.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:8677-8682(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=12950177; DOI=10.1021/bi0300635;
RA Fiset M.E., Gilbert C., Poubelle P.E., Pouliot M.;
RT "Human neutrophils as a source of nociceptin: a novel link between pain and
RT inflammation.";
RL Biochemistry 42:10498-10505(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [9]
RP STRUCTURE BY NMR OF NOCICEPTIN.
RX PubMed=9168905; DOI=10.1006/bbrc.1997.6285;
RA Salvadori S., Picone D., Tancredi T., Guerrini R., Spadaccini R.,
RA Lazarus L.H., Regoli D., Temussi P.A.;
RT "Solution conformation of nociceptin.";
RL Biochem. Biophys. Res. Commun. 233:640-643(1997).
CC -!- FUNCTION: [Nociceptin]: Ligand of the opioid receptor-like receptor
CC OPRL1. It may act as a transmitter in the brain by modulating
CC nociceptive and locomotor behavior. May be involved in neuronal
CC differentiation and development. {ECO:0000250|UniProtKB:P55791}.
CC -!- FUNCTION: [Nocistatin]: Blocks nociceptin action in pain transmission
CC by inhibiting nociceptin-induced hyperalgesia and allodynia.
CC {ECO:0000250|UniProtKB:O62647}.
CC -!- FUNCTION: [Orphanin FQ2]: Has potent analgesic activity.
CC {ECO:0000250|UniProtKB:Q64387}.
CC -!- INTERACTION:
CC PRO_0000008327; P41146: OPRL1; NbExp=2; IntAct=EBI-6656256, EBI-2624699;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13519-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13519-2; Sequence=VSP_055146;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the brain and spinal
CC cord. Also expressed and secreted by peripheral blood neutrophils
CC following degranulation. {ECO:0000269|PubMed:12950177}.
CC -!- PTM: Specific enzymatic cleavages at paired basic residues probably
CC yield other active peptides besides nociceptin.
CC -!- PTM: The N-terminal domain contains 6 conserved cysteines thought to be
CC involved in disulfide bonding and/or processing.
CC -!- SIMILARITY: Belongs to the opioid neuropeptide precursor family.
CC {ECO:0000305}.
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DR EMBL; X97370; CAA66040.1; -; mRNA.
DR EMBL; X97367; CAA66039.1; -; Genomic_DNA.
DR EMBL; X97368; CAA66039.1; JOINED; Genomic_DNA.
DR EMBL; U48263; AAC50651.1; -; mRNA.
DR EMBL; AY335948; AAP94601.1; -; mRNA.
DR EMBL; AK301456; BAH13485.1; -; mRNA.
DR EMBL; BT019334; AAV38141.1; -; mRNA.
DR EMBL; CR541940; CAG46738.1; -; mRNA.
DR EMBL; CR541965; CAG46763.1; -; mRNA.
DR EMBL; AC021678; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471080; EAW63526.1; -; Genomic_DNA.
DR EMBL; CH471080; EAW63527.1; -; Genomic_DNA.
DR EMBL; BC034758; AAH34758.1; -; mRNA.
DR CCDS; CCDS6066.1; -. [Q13519-1]
DR CCDS; CCDS64862.1; -. [Q13519-2]
DR PIR; JC6152; JC6152.
DR RefSeq; NP_001271173.1; NM_001284244.1. [Q13519-2]
DR RefSeq; NP_006219.1; NM_006228.4. [Q13519-1]
DR AlphaFoldDB; Q13519; -.
DR SMR; Q13519; -.
DR BioGRID; 111381; 16.
DR IntAct; Q13519; 2.
DR STRING; 9606.ENSP00000301908; -.
DR BindingDB; Q13519; -.
DR TCDB; 1.C.89.1.3; the dynorphin channel-forming neuropeptide (dynorphin) family.
DR iPTMnet; Q13519; -.
DR PhosphoSitePlus; Q13519; -.
DR BioMuta; PNOC; -.
DR DMDM; 2494348; -.
DR MassIVE; Q13519; -.
DR MaxQB; Q13519; -.
DR PaxDb; Q13519; -.
DR PeptideAtlas; Q13519; -.
DR PRIDE; Q13519; -.
DR ProteomicsDB; 59515; -. [Q13519-1]
DR ProteomicsDB; 6832; -.
DR TopDownProteomics; Q13519-2; -. [Q13519-2]
DR Antibodypedia; 10388; 294 antibodies from 29 providers.
DR DNASU; 5368; -.
DR Ensembl; ENST00000301908.8; ENSP00000301908.3; ENSG00000168081.9. [Q13519-1]
DR Ensembl; ENST00000522209.1; ENSP00000430145.1; ENSG00000168081.9. [Q13519-2]
DR GeneID; 5368; -.
DR KEGG; hsa:5368; -.
DR MANE-Select; ENST00000301908.8; ENSP00000301908.3; NM_006228.5; NP_006219.1.
DR UCSC; uc003xgp.5; human. [Q13519-1]
DR CTD; 5368; -.
DR DisGeNET; 5368; -.
DR GeneCards; PNOC; -.
DR HGNC; HGNC:9163; PNOC.
DR HPA; ENSG00000168081; Group enriched (brain, fallopian tube, lymphoid tissue).
DR MIM; 601459; gene.
DR neXtProt; NX_Q13519; -.
DR OpenTargets; ENSG00000168081; -.
DR PharmGKB; PA33485; -.
DR VEuPathDB; HostDB:ENSG00000168081; -.
DR eggNOG; ENOG502S0DD; Eukaryota.
DR GeneTree; ENSGT00950000183149; -.
DR HOGENOM; CLU_143892_0_0_1; -.
DR InParanoid; Q13519; -.
DR OMA; WTPCTKI; -.
DR OrthoDB; 1486887at2759; -.
DR PhylomeDB; Q13519; -.
DR TreeFam; TF332620; -.
DR PathwayCommons; Q13519; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; Q13519; -.
DR BioGRID-ORCS; 5368; 13 hits in 1061 CRISPR screens.
DR ChiTaRS; PNOC; human.
DR GenomeRNAi; 5368; -.
DR Pharos; Q13519; Tbio.
DR PRO; PR:Q13519; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q13519; protein.
DR Bgee; ENSG00000168081; Expressed in germinal epithelium of ovary and 119 other tissues.
DR ExpressionAtlas; Q13519; baseline and differential.
DR Genevisible; Q13519; HS.
DR GO; GO:0043679; C:axon terminus; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0043025; C:neuronal cell body; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005184; F:neuropeptide hormone activity; TAS:ProtInc.
DR GO; GO:0001515; F:opioid peptide activity; IEA:UniProtKB-KW.
DR GO; GO:0031628; F:opioid receptor binding; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:0007600; P:sensory perception; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR002367; Nociceptin.
DR InterPro; IPR006024; Opioid_neupept.
DR PANTHER; PTHR11438; PTHR11438; 1.
DR Pfam; PF01160; Opiods_neuropep; 1.
DR PRINTS; PR01028; OPIOIDPRCRSR.
DR PRINTS; PR01031; ORPHNNPRCRSR.
DR PROSITE; PS01252; OPIOIDS_PRECURSOR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues; Disulfide bond;
KW Neuropeptide; Neurotransmitter; Opioid peptide; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..95
FT /id="PRO_0000008325"
FT PEPTIDE 98..127
FT /note="Nocistatin"
FT /evidence="ECO:0000305"
FT /id="PRO_0000008326"
FT PEPTIDE 130..146
FT /note="Nociceptin"
FT /evidence="ECO:0000250|UniProtKB:P55791"
FT /id="PRO_0000008327"
FT PEPTIDE 149..165
FT /note="Orphanin FQ2"
FT /evidence="ECO:0000305"
FT /id="PRO_0000008328"
FT PROPEP 169..176
FT /id="PRO_0000008329"
FT VAR_SEQ 1..64
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055146"
SQ SEQUENCE 176 AA; 20295 MW; 8FC8DB4BB094CE6A CRC64;
MKVLLCDLLL LSLFSSVFSS CQRDCLTCQE KLHPALDSFD LEVCILECEE KVFPSPLWTP
CTKVMARSSW QLSPAAPEHV AAALYQPRAS EMQHLRRMPR VRSLFQEQEE PEPGMEEAGE
MEQKQLQKRF GGFTGARKSA RKLANQKRFS EFMRQYLVLS MQSSQRRRTL HQNGNV
