PRLR_HUMAN
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 03-AUG-2022, entry version 230.
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="http://atlasgeneticsoncology.org/Genes/PRLRID42891ch5p14.html";
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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. [P16471-1]
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 GlyGen; P16471; 3 sites.
DR iPTMnet; P16471; -.
DR PhosphoSitePlus; P16471; -.
DR BioMuta; PRLR; -.
DR DMDM; 130321; -.
DR MassIVE; P16471; -.
DR PaxDb; P16471; -.
DR PeptideAtlas; P16471; -.
DR PRIDE; 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; 895 antibodies from 37 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 CTD; 5618; -.
DR DisGeNET; 5618; -.
DR GeneCards; PRLR; -.
DR HGNC; HGNC:9446; PRLR.
DR HPA; ENSG00000113494; Tissue enriched (choroid).
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; YHYELRL; -.
DR OrthoDB; 346239at2759; -.
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; 8 hits in 1072 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 tissues.
DR ExpressionAtlas; P16471; baseline and differential.
DR Genevisible; P16471; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005127; F:ciliary neurotrophic factor receptor binding; IBA:GO_Central.
DR GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR GO; GO:0004923; F:leukemia inhibitory factor receptor activity; IBA:GO_Central.
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: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:0038165; P:oncostatin-M-mediated signaling pathway; IEA:GOC.
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: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; -; 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 InterPro; IPR033230; PRLR.
DR PANTHER; PTHR23036:SF86; PTHR23036:SF86; 2.
DR Pfam; PF09067; EpoR_lig-bind; 1.
DR SMART; SM00060; FN3; 2.
DR SUPFAM; SSF49265; SSF49265; 2.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS01352; HEMATOPO_REC_L_F1; 1.
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
