ID PRLR_HUMAN Reviewed; 622 AA. AC P16471; B2R882; D1MDP1; Q16354; Q8TD75; Q8TD78; Q96P35; Q96P36; Q9BX87; AC Q9UHJ5; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1990, sequence version 1. DT 24-JAN-2024, entry version 238. DE RecName: Full=Prolactin receptor; DE Short=PRL-R; DE Flags: Precursor; GN Name=PRLR; 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] (ISOFORM 1). RX PubMed=2558309; DOI=10.1210/mend-3-9-1455; RA Boutin J.-M., Edery M., Shirota M., Jolicoeur C., Lesueur L., Ali S., RA Gould D., Djiane J., Kelly P.A.; RT "Identification of a cDNA encoding a long form of prolactin receptor in RT human hepatoma and breast cancer cells."; RL Mol. Endocrinol. 3:1455-1461(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RX PubMed=10585417; DOI=10.1074/jbc.274.50.35461; RA Kline J.B., Roehrs H., Clevenger C.V.; RT "Functional characterization of the intermediate isoform of the human RT prolactin receptor."; RL J. Biol. Chem. 274:35461-35468(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10084611; DOI=10.1210/jcem.84.3.5659; RA Hu Z.-Z., Zhuang L., Meng J., Leondires M., Dufau M.L.; RT "The human prolactin receptor gene structure and alternative promoter RT utilization: the generic promoter hPIII and a novel human promoter hP(N)."; RL J. Clin. Endocrinol. Metab. 84:1153-1156(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 6), INTERACTION WITH GH1, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11518703; DOI=10.1074/jbc.m102109200; RA Hu Z.Z., Meng J., Dufau M.L.; RT "Isolation and characterization of two novel forms of the human prolactin RT receptor generated by alternative splicing of a newly identified exon 11."; RL J. Biol. Chem. 276:41086-41094(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Mammary carcinoma; RX PubMed=12351696; DOI=10.1210/me.2001-0033; RA Kline J.B., Rycyzyn M.A., Clevenger C.V.; RT "Characterization of a novel and functional human prolactin receptor RT isoform (deltaS1PRLr) containing only one extracellular fibronectin-like RT domain."; RL Mol. Endocrinol. 16:2310-2322(2002). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4; 6; 7 AND 8), FUNCTION, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12580759; DOI=10.1677/jme.0.0300031; RA Trott J.F., Hovey R.C., Koduri S., Vonderhaar B.K.; RT "Alternative splicing to exon 11 of human prolactin receptor gene results RT in multiple isoforms including a secreted prolactin-binding protein."; RL J. Mol. Endocrinol. 30:31-47(2003). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 9), AND FUNCTION. RX PubMed=20032052; DOI=10.1210/en.2009-0964; RA Pujianto D.A., Curry B.J., Aitken R.J.; RT "Prolactin exerts a prosurvival effect on human spermatozoa via mechanisms RT that involve the stimulation of Akt phosphorylation and suppression of RT caspase activation and capacitation."; RL Endocrinology 151:1269-1279(2010). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Prostate; 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [10] 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 [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; 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 [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-622 (ISOFORM 3). RC TISSUE=Mammary carcinoma; RX PubMed=7768908; DOI=10.1074/jbc.270.22.13133; RA Fuh G., Wells J.A.; RT "Prolactin receptor antagonists that inhibit the growth of breast cancer RT cell lines."; RL J. Biol. Chem. 270:13133-13137(1995). RN [13] RP INTERACTION WITH NEK3 AND VAV2. RX PubMed=15618286; DOI=10.1210/me.2004-0443; RA Miller S.L., DeMaria J.E., Freier D.O., Riegel A.M., Clevenger C.V.; RT "Novel association of Vav2 and Nek3 modulates signaling through the human RT prolactin receptor."; RL Mol. Endocrinol. 19:939-949(2005). RN [14] RP SUBUNIT, AND ZINC-BINDING SITES. RX PubMed=16546209; DOI=10.1016/j.jmb.2006.02.038; RA Walsh S.T., Kossiakoff A.A.; RT "Crystal structure and site 1 binding energetics of human placental RT lactogen."; RL J. Mol. Biol. 358:773-784(2006). RN [15] RP INTERACTION WITH SMARCA1. RX PubMed=16740656; DOI=10.1210/me.2005-0213; RA Lazzaro M.A., Pepin D., Pescador N., Murphy B.D., Vanderhyden B.C., RA Picketts D.J.; RT "The imitation switch protein SNF2L regulates steroidogenic acute RT regulatory protein expression during terminal differentiation of ovarian RT granulosa cells."; RL Mol. Endocrinol. 20:2406-2417(2006). RN [16] RP VARIANT MFAB LEU-170, AND CHARACTERIZATION OF VARIANT MFAB LEU-170. RX PubMed=18779591; DOI=10.1073/pnas.0800685105; RA Bogorad R.L., Courtillot C., Mestayer C., Bernichtein S., Harutyunyan L., RA Jomain J.B., Bachelot A., Kuttenn F., Kelly P.A., Goffin V., Touraine P., RA Bachelot A., Belaroussi B., Bensimhon J., Berdah J., Blin M.J., RA Boudinet A., Brethon B., Bricaire C., Caby J., Caillaud G., Carel J.C., RA Chabbert-Buffet N., Charitanski H., Chretien C., Clough K., Courtillot C., RA Delattre G., Denys I., Desthieux-Ngo K., Detoeuf M., Dhainault C., RA Duflos C., Fiori O., Genestie C., Gibaud G., Gompel A., Gracia C., RA Grimard A., Hofman C., Hofman H., Kuttenn F., Laki F., Lanty C., RA Lefranc J.P., Le Frere-Belda M.A., Leger D., Martinez F., May A., Meng L., RA Nos C., Pelletier D., Perrin A., Plu-Bureau G., Raccah-Tebbeca B., RA Saiovici J.C., Salmon R., Sibout M., Sigal-Zafrani B., Thalabard J.C., RA Thibaud E., Thoury A., Touraine P., Triana-Rabi K.B., Uzan S., Viriot J., RA Yacoub S.; RT "Identification of a gain-of-function mutation of the prolactin receptor in RT women with benign breast tumors."; RL Proc. Natl. Acad. Sci. U.S.A. 105:14533-14538(2008). RN [17] RP VARIANT HPRL ARG-212, AND CHARACTERIZATION OF VARIANT HPRL ARG-212. RX PubMed=24195502; DOI=10.1056/nejmoa1307557; RA Newey P.J., Gorvin C.M., Cleland S.J., Willberg C.B., Bridge M., RA Azharuddin M., Drummond R.S., van der Merwe P.A., Klenerman P., Bountra C., RA Thakker R.V.; RT "Mutant prolactin receptor and familial hyperprolactinemia."; RL N. Engl. J. Med. 369:2012-2020(2013). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 25-235. RX PubMed=7984244; DOI=10.1038/372478a0; RA Somers W., Ultsch M., de Vos A.M., Kossiakoff A.A.; RT "The X-ray structure of a growth hormone-prolactin receptor complex."; RL Nature 372:478-481(1994). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 25-234 IN COMPLEX WITH PRL, RP SUBUNIT, AND DISULFIDE BONDS. RX PubMed=18467331; DOI=10.1074/jbc.m801202200; RA Svensson L.A., Bondensgaard K., Noerskov-Lauritsen L., Christensen L., RA Becker P., Andersen M.D., Maltesen M.J., Rand K.D., Breinholt J.; RT "Crystal structure of a prolactin receptor antagonist bound to the RT extracellular domain of the prolactin receptor."; RL J. Biol. Chem. 283:19085-19094(2008). CC -!- FUNCTION: This is a receptor for the anterior pituitary hormone CC prolactin (PRL). Acts as a prosurvival factor for spermatozoa by CC inhibiting sperm capacitation through suppression of SRC kinase CC activation and stimulation of AKT. Isoform 4 is unable to transduce CC prolactin signaling. Isoform 6 is unable to transduce prolactin CC signaling. {ECO:0000269|PubMed:12580759, ECO:0000269|PubMed:20032052}. CC -!- SUBUNIT: Homodimer upon hormone binding. Interacts with SMARCA1. CC Interacts with GH1. Interacts with CSH. Interacts with NEK3 and VAV2 CC and this interaction is prolactin-dependent. CC {ECO:0000269|PubMed:11518703, ECO:0000269|PubMed:15618286, CC ECO:0000269|PubMed:16546209, ECO:0000269|PubMed:16740656, CC ECO:0000269|PubMed:18467331}. CC -!- INTERACTION: CC P16471; Q9Y5U4: INSIG2; NbExp=3; IntAct=EBI-476182, EBI-8503746; CC P16471; Q8IY26: PLPP6; NbExp=3; IntAct=EBI-476182, EBI-11721828; CC P16471; P63104: YWHAZ; NbExp=3; IntAct=EBI-476182, EBI-347088; CC P16471-1; P01236: PRL; NbExp=2; IntAct=EBI-15968347, EBI-6903064; CC P16471-7; P01236: PRL; NbExp=4; IntAct=EBI-6903057, EBI-6903064; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:11518703, CC ECO:0000269|PubMed:12580759}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:11518703, ECO:0000269|PubMed:12580759}. CC -!- SUBCELLULAR LOCATION: [Isoform 7]: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=9; CC Name=1; CC IsoId=P16471-1; Sequence=Displayed; CC Name=2; Synonyms=Delta-S1; CC IsoId=P16471-2; Sequence=VSP_001720; CC Name=3; CC IsoId=P16471-3; Sequence=VSP_012620, VSP_012621; CC Name=4; Synonyms=SF1a, Short form 1a; CC IsoId=P16471-4; Sequence=VSP_026537, VSP_026539; CC Name=5; Synonyms=Intermediate; CC IsoId=P16471-5; Sequence=VSP_026536, VSP_026538; CC Name=6; Synonyms=SF1b, Short form 1b; CC IsoId=P16471-6; Sequence=VSP_026534, VSP_026535; CC Name=7; Synonyms=Delta 7/11; CC IsoId=P16471-7; Sequence=VSP_026532, VSP_026533; CC Name=8; Synonyms=Delta 4-SF1b; CC IsoId=P16471-8; Sequence=VSP_026531, VSP_026534, VSP_026535; CC Name=9; Synonyms=SF1c, Short form 1c; CC IsoId=P16471-9; Sequence=VSP_047882, VSP_047883; CC -!- TISSUE SPECIFICITY: Expressed in breast, placenta, kidney, liver and CC pancreas. {ECO:0000269|PubMed:11518703, ECO:0000269|PubMed:12580759}. CC -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein CC folding and thereby efficient intracellular transport and cell-surface CC receptor binding. CC -!- DOMAIN: The box 1 motif is required for JAK interaction and/or CC activation. CC -!- DISEASE: Multiple fibroadenomas of the breast (MFAB) [MIM:615554]: A CC benign breast disease marked by lobuloalveolar growth with abnormally CC high proliferation of the epithelium, and characterized by the presence CC of more than 3 fibroadenomas in one breast. Fibroadenomas are adenomas CC containing fibrous tissue. {ECO:0000269|PubMed:18779591}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Hyperprolactinemia (HPRL) [MIM:615555]: A disorder CC characterized by increased levels of prolactin in the blood not CC associated with gestation or the puerperium. HPRL may result in CC infertility, hypogonadism, and galactorrhea. CC {ECO:0000269|PubMed:24195502}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: Soluble isoform that appears specific for CC the BT-474 breast cancer cell line. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Includes exon 11. Does not transduce CC prolactin signaling. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Produced by deletion of part of exon 10 and CC frameshift. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 6]: Does not transduce prolactin signaling. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 7]: Splices from exon 7 to exon 11. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 8]: SF1b with deletion of exon 4. May be CC produced at very low levels due to a premature stop codon in the mRNA, CC leading to nonsense-mediated mRNA decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 1 CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42891/PRLR"; 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; M31661; AAA60174.1; -; mRNA. DR EMBL; AF166329; AAD49855.1; -; mRNA. DR EMBL; AF091870; AAD32032.1; -; Genomic_DNA. DR EMBL; AF091863; AAD32032.1; JOINED; Genomic_DNA. DR EMBL; AF091864; AAD32032.1; JOINED; Genomic_DNA. DR EMBL; AF091865; AAD32032.1; JOINED; Genomic_DNA. DR EMBL; AF091866; AAD32032.1; JOINED; Genomic_DNA. DR EMBL; AF091867; AAD32032.1; JOINED; Genomic_DNA. DR EMBL; AF091868; AAD32032.1; JOINED; Genomic_DNA. DR EMBL; AF091869; AAD32032.1; JOINED; Genomic_DNA. DR EMBL; AF349939; AAK32703.1; -; mRNA. DR EMBL; AF416618; AAL23914.1; -; mRNA. DR EMBL; AF416619; AAL23915.1; -; mRNA. DR EMBL; AF492470; AAM18048.1; -; mRNA. DR EMBL; AF493069; AAM11661.1; -; mRNA. DR EMBL; GU133399; ACZ04321.1; -; mRNA. DR EMBL; AK313270; BAG36079.1; -; mRNA. DR EMBL; AC010368; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC091851; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471119; EAW55919.1; -; Genomic_DNA. DR EMBL; BC059392; AAH59392.1; -; mRNA. DR EMBL; S78505; AAB34470.1; -; mRNA. DR CCDS; CCDS3909.1; -. [P16471-1] DR CCDS; CCDS56358.1; -. [P16471-2] DR CCDS; CCDS56359.1; -. [P16471-7] DR CCDS; CCDS56360.1; -. [P16471-6] DR CCDS; CCDS56361.1; -. [P16471-4] DR CCDS; CCDS56362.1; -. [P16471-5] DR PIR; A40144; A40144. DR PIR; A59405; A59405. DR PIR; B59405; B59405. DR RefSeq; NP_000940.1; NM_000949.6. [P16471-1] DR RefSeq; NP_001191243.1; NM_001204314.2. [P16471-2] DR RefSeq; NP_001191244.1; NM_001204315.1. [P16471-5] DR RefSeq; NP_001191245.1; NM_001204316.1. [P16471-4] DR RefSeq; NP_001191246.1; NM_001204317.1. [P16471-6] DR RefSeq; NP_001191247.1; NM_001204318.1. [P16471-7] DR RefSeq; XP_006714547.1; XM_006714484.2. [P16471-1] DR RefSeq; XP_011512370.1; XM_011514068.2. [P16471-1] DR RefSeq; XP_011512371.1; XM_011514069.2. DR RefSeq; XP_016865135.1; XM_017009646.1. DR PDB; 1BP3; X-ray; 2.90 A; B=25-235. DR PDB; 2LFG; NMR; -; A=123-234. DR PDB; 2N7I; NMR; -; A=230-264. DR PDB; 3D48; X-ray; 2.50 A; R=25-234. DR PDB; 3MZG; X-ray; 2.10 A; B=26-234. DR PDB; 3N06; X-ray; 2.00 A; B=26-234. DR PDB; 3N0P; X-ray; 2.10 A; B=26-234. DR PDB; 3NCB; X-ray; 2.10 A; B=26-234. DR PDB; 3NCC; X-ray; 2.50 A; B=26-234. DR PDB; 3NCE; X-ray; 2.00 A; B=26-234. DR PDB; 3NCF; X-ray; 2.80 A; B=26-234. DR PDB; 4I18; X-ray; 3.24 A; C/R=25-235. DR PDBsum; 1BP3; -. DR PDBsum; 2LFG; -. DR PDBsum; 2N7I; -. DR PDBsum; 3D48; -. DR PDBsum; 3MZG; -. DR PDBsum; 3N06; -. DR PDBsum; 3N0P; -. DR PDBsum; 3NCB; -. DR PDBsum; 3NCC; -. DR PDBsum; 3NCE; -. DR PDBsum; 3NCF; -. DR PDBsum; 4I18; -. DR AlphaFoldDB; P16471; -. DR BMRB; P16471; -. DR SMR; P16471; -. DR BioGRID; 111603; 17. DR CORUM; P16471; -. DR DIP; DIP-288N; -. DR ELM; P16471; -. DR IntAct; P16471; 8. DR MINT; P16471; -. DR STRING; 9606.ENSP00000482954; -. DR BindingDB; P16471; -. DR ChEMBL; CHEMBL5588; -. DR DrugBank; DB16220; Lonapegsomatropin. DR DrugBank; DB00052; Somatotropin. DR TCDB; 8.A.152.2.8; the interleukin receptor (ilr) family. DR GlyCosmos; P16471; 3 sites, No reported glycans. DR GlyGen; P16471; 3 sites. DR iPTMnet; P16471; -. DR PhosphoSitePlus; P16471; -. DR BioMuta; PRLR; -. DR DMDM; 130321; -. DR MassIVE; P16471; -. DR PaxDb; 9606-ENSP00000482954; -. DR PeptideAtlas; P16471; -. DR ProteomicsDB; 12725; -. DR ProteomicsDB; 53366; -. [P16471-1] DR ProteomicsDB; 53367; -. [P16471-2] DR ProteomicsDB; 53368; -. [P16471-3] DR ProteomicsDB; 53369; -. [P16471-4] DR ProteomicsDB; 53370; -. [P16471-5] DR ProteomicsDB; 53371; -. [P16471-6] DR ProteomicsDB; 53372; -. [P16471-7] DR ProteomicsDB; 53373; -. [P16471-8] DR ABCD; P16471; 50 sequenced antibodies. DR Antibodypedia; 10116; 996 antibodies from 38 providers. DR DNASU; 5618; -. DR Ensembl; ENST00000231423.7; ENSP00000231423.3; ENSG00000113494.17. [P16471-4] DR Ensembl; ENST00000310101.9; ENSP00000309008.5; ENSG00000113494.17. [P16471-5] DR Ensembl; ENST00000348262.7; ENSP00000311613.3; ENSG00000113494.17. [P16471-7] DR Ensembl; ENST00000509140.5; ENSP00000425300.2; ENSG00000113494.17. [P16471-6] DR Ensembl; ENST00000511486.5; ENSP00000422556.1; ENSG00000113494.17. [P16471-2] DR Ensembl; ENST00000513753.5; ENSP00000424841.1; ENSG00000113494.17. [P16471-6] DR Ensembl; ENST00000514088.5; ENSP00000422935.2; ENSG00000113494.17. [P16471-7] DR Ensembl; ENST00000542609.5; ENSP00000441813.2; ENSG00000113494.17. [P16471-4] DR Ensembl; ENST00000618457.5; ENSP00000482954.1; ENSG00000113494.17. [P16471-1] DR Ensembl; ENST00000619676.4; ENSP00000484768.1; ENSG00000113494.17. [P16471-5] DR Ensembl; ENST00000620785.4; ENSP00000482689.1; ENSG00000113494.17. [P16471-2] DR GeneID; 5618; -. DR KEGG; hsa:5618; -. DR MANE-Select; ENST00000618457.5; ENSP00000482954.1; NM_000949.7; NP_000940.1. DR UCSC; uc003jjg.3; human. [P16471-1] DR AGR; HGNC:9446; -. DR CTD; 5618; -. DR DisGeNET; 5618; -. DR GeneCards; PRLR; -. DR HGNC; HGNC:9446; PRLR. DR HPA; ENSG00000113494; Tissue enhanced (choroid plexus, parathyroid gland). DR MalaCards; PRLR; -. DR MIM; 176761; gene. DR MIM; 615554; phenotype. DR MIM; 615555; phenotype. DR neXtProt; NX_P16471; -. DR OpenTargets; ENSG00000113494; -. DR Orphanet; 397685; Familial hyperprolactinemia. DR PharmGKB; PA33791; -. DR VEuPathDB; HostDB:ENSG00000113494; -. DR eggNOG; ENOG502R22A; Eukaryota. DR GeneTree; ENSGT00940000154851; -. DR HOGENOM; CLU_017892_1_0_1; -. DR InParanoid; P16471; -. DR OMA; ANITCTW; -. DR OrthoDB; 5312906at2759; -. DR PhylomeDB; P16471; -. DR TreeFam; TF330851; -. DR PathwayCommons; P16471; -. DR Reactome; R-HSA-1170546; Prolactin receptor signaling. DR Reactome; R-HSA-982772; Growth hormone receptor signaling. DR SignaLink; P16471; -. DR SIGNOR; P16471; -. DR BioGRID-ORCS; 5618; 10 hits in 1156 CRISPR screens. DR ChiTaRS; PRLR; human. DR EvolutionaryTrace; P16471; -. DR GenomeRNAi; 5618; -. DR Pharos; P16471; Tbio. DR PRO; PR:P16471; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P16471; Protein. DR Bgee; ENSG00000113494; Expressed in placenta and 152 other cell types or tissues. DR ExpressionAtlas; P16471; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0031904; C:endosome lumen; TAS:Reactome. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central. DR GO; GO:0008289; F:lipid binding; IPI:DisProt. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0017046; F:peptide hormone binding; IPI:BHF-UCL. DR GO; GO:0004925; F:prolactin receptor activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl. DR GO; GO:0042976; P:activation of Janus kinase activity; IDA:UniProtKB. DR GO; GO:0007171; P:activation of transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0097011; P:cellular response to granulocyte macrophage colony-stimulating factor stimulus; IEA:Ensembl. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0007566; P:embryo implantation; TAS:ProtInc. DR GO; GO:0007595; P:lactation; TAS:ProtInc. DR GO; GO:0060749; P:mammary gland alveolus development; IEA:Ensembl. DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; IEA:Ensembl. DR GO; GO:0060736; P:prostate gland growth; IEA:Ensembl. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IEA:Ensembl. DR GO; GO:0030155; P:regulation of cell adhesion; IEA:Ensembl. DR GO; GO:0030856; P:regulation of epithelial cell differentiation; IEA:Ensembl. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR GO; GO:0006694; P:steroid biosynthetic process; NAS:UniProtKB. DR CDD; cd00063; FN3; 2. DR DisProt; DP01106; -. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR015152; Growth/epo_recpt_lig-bind. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003528; Long_hematopoietin_rcpt_CS. DR PANTHER; PTHR23036; CYTOKINE RECEPTOR; 1. DR PANTHER; PTHR23036:SF86; PROLACTIN RECEPTOR; 1. DR Pfam; PF09067; EpoR_lig-bind; 1. DR SMART; SM00060; FN3; 2. DR SUPFAM; SSF49265; Fibronectin type III; 2. DR PROSITE; PS50853; FN3; 2. DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1. DR Genevisible; P16471; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; Disulfide bond; KW Glycoprotein; Membrane; Metal-binding; Receptor; Reference proteome; KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix; Zinc. FT SIGNAL 1..24 FT CHAIN 25..622 FT /note="Prolactin receptor" FT /id="PRO_0000010977" FT TOPO_DOM 25..234 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 235..258 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 259..622 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 27..128 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 129..229 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT REGION 326..378 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 461..505 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 520..545 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 215..219 FT /note="WSXWS motif" FT MOTIF 267..275 FT /note="Box 1 motif" FT COMPBIAS 462..485 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 211 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT BINDING 212 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT CARBOHYD 59 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 104 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 233 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 36..46 FT /evidence="ECO:0000269|PubMed:18467331" FT DISULFID 75..86 FT /evidence="ECO:0000269|PubMed:18467331" FT VAR_SEQ 1..71 FT /note="Missing (in isoform 8)" FT /evidence="ECO:0000303|PubMed:12580759" FT /id="VSP_026531" FT VAR_SEQ 24..124 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12351696" FT /id="VSP_001720" FT VAR_SEQ 229..268 FT /note="DFTMNDTTVWISVAVLSAVICLIIVWAVALKGYSMVTCIF -> GDPLMLGA FT SHYKNLKSYRPRKISSQGRLAVFTKATLTTVQ (in isoform 7)" FT /evidence="ECO:0000303|PubMed:12580759" FT /id="VSP_026532" FT VAR_SEQ 229..230 FT /note="DF -> AW (in isoform 3)" FT /evidence="ECO:0000303|PubMed:7768908" FT /id="VSP_012620" FT VAR_SEQ 231..622 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:7768908" FT /id="VSP_012621" FT VAR_SEQ 269..622 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:12580759" FT /id="VSP_026533" FT VAR_SEQ 286..309 FT /note="KGKSEELLSALGCQDFPPTSDYED -> DRLCTPGRCCVSTGLTDLDYSCST FT (in isoform 9)" FT /evidence="ECO:0000303|PubMed:20032052" FT /id="VSP_047882" FT VAR_SEQ 286..288 FT /note="KGK -> VTP (in isoform 6 and isoform 8)" FT /evidence="ECO:0000303|PubMed:11518703, FT ECO:0000303|PubMed:12580759" FT /id="VSP_026534" FT VAR_SEQ 289..622 FT /note="Missing (in isoform 6 and isoform 8)" FT /evidence="ECO:0000303|PubMed:11518703, FT ECO:0000303|PubMed:12580759" FT /id="VSP_026535" FT VAR_SEQ 310..622 FT /note="Missing (in isoform 9)" FT /evidence="ECO:0000303|PubMed:20032052" FT /id="VSP_047883" FT VAR_SEQ 337..349 FT /note="GMKPTYLDPDTDS -> EREQRQAQEARDS (in isoform 5)" FT /evidence="ECO:0000303|PubMed:10585417" FT /id="VSP_026536" FT VAR_SEQ 338..376 FT /note="MKPTYLDPDTDSGRGSCDSPSLLSEKCEEPQANPSTFYD -> DPLMLGASH FT YKNLKSYRPRKISSQGRLAVFTKATLTTVQ (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11518703, FT ECO:0000303|PubMed:12580759" FT /id="VSP_026537" FT VAR_SEQ 350..622 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:10585417" FT /id="VSP_026538" FT VAR_SEQ 377..622 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:11518703, FT ECO:0000303|PubMed:12580759" FT /id="VSP_026539" FT VARIANT 100 FT /note="I -> V (in dbSNP:rs2228482)" FT /id="VAR_049172" FT VARIANT 170 FT /note="I -> L (in MFAB; confers constitutive activity; FT dbSNP:rs72478580)" FT /evidence="ECO:0000269|PubMed:18779591" FT /id="VAR_070894" FT VARIANT 212 FT /note="H -> R (in HPRL; loss of function; FT dbSNP:rs398122522)" FT /evidence="ECO:0000269|PubMed:24195502" FT /id="VAR_070895" FT STRAND 32..42 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 44..49 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 52..54 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 58..66 FT /evidence="ECO:0007829|PDB:3N06" FT TURN 67..69 FT /evidence="ECO:0007829|PDB:3NCC" FT STRAND 85..88 FT /evidence="ECO:0007829|PDB:3N06" FT HELIX 90..92 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 99..107 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 110..113 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 117..119 FT /evidence="ECO:0007829|PDB:3N06" FT HELIX 121..123 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 131..138 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 146..152 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:2LFG" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:3N0P" FT STRAND 166..173 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 181..186 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 189..193 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 201..213 FT /evidence="ECO:0007829|PDB:3N06" FT STRAND 222..225 FT /evidence="ECO:0007829|PDB:3N06" FT HELIX 230..232 FT /evidence="ECO:0007829|PDB:4I18" FT HELIX 234..254 FT /evidence="ECO:0007829|PDB:2N7I" FT TURN 255..257 FT /evidence="ECO:0007829|PDB:2N7I" FT STRAND 258..262 FT /evidence="ECO:0007829|PDB:2N7I" SQ SEQUENCE 622 AA; 69506 MW; DB7FD0328608C787 CRC64; MKENVASATV FTLLLFLNTC LLNGQLPPGK PEIFKCRSPN KETFTCWWRP GTDGGLPTNY SLTYHREGET LMHECPDYIT GGPNSCHFGK QYTSMWRTYI MMVNATNQMG SSFSDELYVD VTYIVQPDPP LELAVEVKQP EDRKPYLWIK WSPPTLIDLK TGWFTLLYEI RLKPEKAAEW EIHFAGQQTE FKILSLHPGQ KYLVQVRCKP DHGYWSAWSP ATFIQIPSDF TMNDTTVWIS VAVLSAVICL IIVWAVALKG YSMVTCIFPP VPGPKIKGFD AHLLEKGKSE ELLSALGCQD FPPTSDYEDL LVEYLEVDDS EDQHLMSVHS KEHPSQGMKP TYLDPDTDSG RGSCDSPSLL SEKCEEPQAN PSTFYDPEVI EKPENPETTH TWDPQCISME GKIPYFHAGG SKCSTWPLPQ PSQHNPRSSY HNITDVCELA VGPAGAPATL LNEAGKDALK SSQTIKSREE GKATQQREVE SFHSETDQDT PWLLPQEKTP FGSAKPLDYV EIHKVNKDGA LSLLPKQREN SGKPKKPGTP ENNKEYAKVS GVMDNNILVL VPDPHAKNVA CFEESAKEAP PSLEQNQAEK ALANFTATSS KCRLQLGGLD YLDPACFTHS FH //