ID   PAQR8_HUMAN             Reviewed;         354 AA.
AC   Q8TEZ7; B2RCF6; Q86WL0; Q8N6D3; Q9HD02;
DT   16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   24-JAN-2024, entry version 144.
DE   RecName: Full=Membrane progestin receptor beta {ECO:0000303|PubMed:23763432};
DE            Short=mPR beta {ECO:0000303|PubMed:23763432};
DE   AltName: Full=Lysosomal membrane protein in brain 1 {ECO:0000303|PubMed:11676489};
DE   AltName: Full=Membrane progesterone P4 receptor beta {ECO:0000303|PubMed:23763432};
DE   AltName: Full=Membrane progesterone receptor beta {ECO:0000303|PubMed:23763432};
DE   AltName: Full=Progesterone and adipoQ receptor family member 8;
DE   AltName: Full=Progestin and adipoQ receptor family member 8 {ECO:0000303|PubMed:16044242};
DE   AltName: Full=Progestin and adipoQ receptor family member VIII;
GN   Name=PAQR8 {ECO:0000312|HGNC:HGNC:15708};
GN   Synonyms=C6orf33 {ECO:0000312|HGNC:HGNC:15708}, LMPB1, MPRB;
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], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Brain;
RX   PubMed=11676489; DOI=10.1006/bbrc.2001.5825;
RA   Suzuki T., Ganesh S., Agarwala K.L., Morita R., Sugimoto Y., Inazawa J.,
RA   Delgado-Escueta A.V., Yamakawa K.;
RT   "A novel gene in the chromosomal region for juvenile myoclonic epilepsy on
RT   6p12 encodes a brain-specific lysosomal membrane protein.";
RL   Biochem. Biophys. Res. Commun. 288:626-636(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=16044242; DOI=10.1007/s00239-004-0375-2;
RA   Tang Y.T., Hu T., Arterburn M., Boyle B., Bright J.M., Emtage P.C.,
RA   Funk W.D.;
RT   "PAQR proteins: a novel membrane receptor family defined by an ancient 7-
RT   transmembrane pass motif.";
RL   J. Mol. Evol. 61:372-380(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 133-354, AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=12601167; DOI=10.1073/pnas.0436133100;
RA   Zhu Y., Bond J., Thomas P.;
RT   "Identification, classification, and partial characterization of genes in
RT   humans and other vertebrates homologous to a fish membrane progestin
RT   receptor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:2237-2242(2003).
RN   [7]
RP   REVIEW.
RX   PubMed=12606724; DOI=10.1073/pnas.0530224100;
RA   Hammes S.R.;
RT   "The further redefining of steroid-mediated signaling.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:2168-2170(2003).
RN   [8]
RP   FUNCTION, REVIEW, AND SUBCELLULAR LOCATION.
RX   PubMed=23763432; DOI=10.1111/jne.12060;
RA   Petersen S.L., Intlekofer K.A., Moura-Conlon P.J., Brewer D.N.,
RA   Del Pino Sans J., Lopez J.A.;
RT   "Nonclassical progesterone signalling molecules in the nervous system.";
RL   J. Neuroendocrinol. 25:991-1001(2013).
RN   [9]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=23161870; DOI=10.1210/en.2012-1772;
RA   Pang Y., Dong J., Thomas P.;
RT   "Characterization, neurosteroid binding and brain distribution of human
RT   membrane progesterone receptors delta and {epsilon} (mPRdelta and
RT   mPR{epsilon}) and mPRdelta involvement in neurosteroid inhibition of
RT   apoptosis.";
RL   Endocrinology 154:283-295(2013).
CC   -!- FUNCTION: Plasma membrane progesterone (P4) receptor coupled to G
CC       proteins (PubMed:23763432). Seems to act through a G(i) mediated
CC       pathway (PubMed:23763432). May be involved in oocyte maturation (By
CC       similarity). Also binds dehydroepiandrosterone (DHEA), pregnanolone,
CC       pregnenolone and allopregnanolone (PubMed:23161870).
CC       {ECO:0000250|UniProtKB:Q80ZE5, ECO:0000269|PubMed:23161870,
CC       ECO:0000303|PubMed:23763432}.
CC   -!- INTERACTION:
CC       Q8TEZ7; Q08426: EHHADH; NbExp=3; IntAct=EBI-12847818, EBI-2339219;
CC       Q8TEZ7; O95214: LEPROTL1; NbExp=3; IntAct=EBI-12847818, EBI-750776;
CC       Q8TEZ7; Q00013: MPP1; NbExp=3; IntAct=EBI-12847818, EBI-711788;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11676489,
CC       ECO:0000303|PubMed:23763432}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Colocalizes with a lysosomal protein CTSD/cathepsin
CC       D. {ECO:0000269|PubMed:11676489}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the hypothalamus
CC       (PubMed:23161870). Also expressed in spinal cord, kidney and testis.
CC       {ECO:0000269|PubMed:11676489, ECO:0000269|PubMed:12601167,
CC       ECO:0000269|PubMed:16044242, ECO:0000269|PubMed:23161870}.
CC   -!- MISCELLANEOUS: Non-classical progesterone receptors involved in
CC       extranuclear signaling are classified in 2 groups: the class II
CC       progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5,
CC       PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding
CC       protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).
CC       {ECO:0000303|PubMed:23763432}.
CC   -!- SIMILARITY: Belongs to the ADIPOR family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAR08374.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AF347029; AAL79777.2; -; mRNA.
DR   EMBL; AY424286; AAR08374.1; ALT_INIT; mRNA.
DR   EMBL; AK315088; BAG37553.1; -; mRNA.
DR   EMBL; AL136125; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC030664; AAH30664.2; -; mRNA.
DR   EMBL; AF313619; AAO47232.1; -; mRNA.
DR   CCDS; CCDS4941.1; -.
DR   RefSeq; NP_588608.1; NM_133367.4.
DR   AlphaFoldDB; Q8TEZ7; -.
DR   SMR; Q8TEZ7; -.
DR   BioGRID; 124469; 3.
DR   IntAct; Q8TEZ7; 3.
DR   STRING; 9606.ENSP00000406197; -.
DR   TCDB; 1.C.113.1.12; the hemolysin iii (hly iii) family.
DR   iPTMnet; Q8TEZ7; -.
DR   PhosphoSitePlus; Q8TEZ7; -.
DR   BioMuta; PAQR8; -.
DR   DMDM; 51316493; -.
DR   MassIVE; Q8TEZ7; -.
DR   PaxDb; 9606-ENSP00000406197; -.
DR   PeptideAtlas; Q8TEZ7; -.
DR   ProteomicsDB; 74529; -.
DR   Antibodypedia; 30905; 132 antibodies from 23 providers.
DR   DNASU; 85315; -.
DR   Ensembl; ENST00000360726.3; ENSP00000353953.3; ENSG00000170915.9.
DR   Ensembl; ENST00000442253.3; ENSP00000406197.2; ENSG00000170915.9.
DR   GeneID; 85315; -.
DR   KEGG; hsa:85315; -.
DR   MANE-Select; ENST00000442253.3; ENSP00000406197.2; NM_133367.5; NP_588608.1.
DR   UCSC; uc003pao.4; human.
DR   AGR; HGNC:15708; -.
DR   CTD; 85315; -.
DR   DisGeNET; 85315; -.
DR   GeneCards; PAQR8; -.
DR   HGNC; HGNC:15708; PAQR8.
DR   HPA; ENSG00000170915; Tissue enhanced (brain).
DR   MIM; 607780; gene.
DR   neXtProt; NX_Q8TEZ7; -.
DR   OpenTargets; ENSG00000170915; -.
DR   PharmGKB; PA25934; -.
DR   VEuPathDB; HostDB:ENSG00000170915; -.
DR   eggNOG; KOG0748; Eukaryota.
DR   GeneTree; ENSGT00940000159860; -.
DR   HOGENOM; CLU_052356_0_0_1; -.
DR   InParanoid; Q8TEZ7; -.
DR   OMA; CAGCCFA; -.
DR   OrthoDB; 373478at2759; -.
DR   PhylomeDB; Q8TEZ7; -.
DR   TreeFam; TF319738; -.
DR   PathwayCommons; Q8TEZ7; -.
DR   SignaLink; Q8TEZ7; -.
DR   BioGRID-ORCS; 85315; 18 hits in 1149 CRISPR screens.
DR   ChiTaRS; PAQR8; human.
DR   GeneWiki; PAQR8; -.
DR   GenomeRNAi; 85315; -.
DR   Pharos; Q8TEZ7; Tbio.
DR   PRO; PR:Q8TEZ7; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; Q8TEZ7; Protein.
DR   Bgee; ENSG00000170915; Expressed in inferior vagus X ganglion and 177 other cell types or tissues.
DR   ExpressionAtlas; Q8TEZ7; baseline and differential.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0003707; F:nuclear steroid receptor activity; IBA:GO_Central.
DR   GO; GO:0005496; F:steroid binding; IBA:GO_Central.
DR   GO; GO:0048477; P:oogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0048545; P:response to steroid hormone; IBA:GO_Central.
DR   InterPro; IPR004254; AdipoR/HlyIII-related.
DR   PANTHER; PTHR20855; ADIPOR/PROGESTIN RECEPTOR-RELATED; 1.
DR   PANTHER; PTHR20855:SF22; MEMBRANE PROGESTIN RECEPTOR BETA; 1.
DR   Pfam; PF03006; HlyIII; 1.
DR   Genevisible; Q8TEZ7; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Developmental protein; Differentiation; Lipid-binding;
KW   Membrane; Oogenesis; Receptor; Reference proteome; Steroid-binding;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..354
FT                   /note="Membrane progestin receptor beta"
FT                   /id="PRO_0000218840"
FT   TOPO_DOM        1..75
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..96
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        97..111
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        112..132
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        133..174
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        175..195
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        196..213
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        214..234
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        235..243
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        244..264
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        265..283
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        284..304
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        305..319
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        320..340
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        341..354
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   354 AA;  40464 MW;  B0ECCD9C54C0CA24 CRC64;
     MTTAILERLS TLSVSGQQLR RLPKILEDGL PKMPCTVPET DVPQLFREPY IRTGYRPTGH
     EWRYYFFSLF QKHNEVVNVW THLLAALAVL LRFWAFAEAE ALPWASTHSL PLLLFILSSI
     TYLTCSLLAH LLQSKSELSH YTFYFVDYVG VSVYQYGSAL AHFFYSSDQA WYDRFWLFFL
     PAAAFCGWLS CAGCCYAKYR YRRPYPVMRK ICQVVPAGLA FILDISPVAH RVALCHLAGC
     QEQAAWYHTL QILFFLVSAY FFSCPVPEKY FPGSCDIVGH GHQIFHAFLS ICTLSQLEAI
     LLDYQGRQEI FLQRHGPLSV HMACLSFFFL AACSAATAAL LRHKVKARLT KKDS
//