NameProlactin receptor
Synonyms
  • PRL-R
Gene NamePRLR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000687|Prolactin receptor
MKENVASATVFTLLLFLNTCLLNGQLPPGKPEIFKCRSPNKETFTCWWRPGTDGGLPTNY
SLTYHREGETLMHECPDYITGGPNSCHFGKQYTSMWRTYIMMVNATNQMGSSFSDELYVD
VTYIVQPDPPLELAVEVKQPEDRKPYLWIKWSPPTLIDLKTGWFTLLYEIRLKPEKAAEW
EIHFAGQQTEFKILSLHPGQKYLVQVRCKPDHGYWSAWSPATFIQIPSDFTMNDTTVWIS
VAVLSAVICLIIVWAVALKGYSMVTCIFPPVPGPKIKGFDAHLLEKGKSEELLSALGCQD
FPPTSDYEDLLVEYLEVDDSEDQHLMSVHSKEHPSQGMKPTYLDPDTDSGRGSCDSPSLL
SEKCEEPQANPSTFYDPEVIEKPENPETTHTWDPQCISMEGKIPYFHAGGSKCSTWPLPQ
PSQHNPRSSYHNITDVCELAVGPAGAPATLLNEAGKDALKSSQTIKSREEGKATQQREVE
SFHSETDQDTPWLLPQEKTPFGSAKPLDYVEIHKVNKDGALSLLPKQRENSGKPKKPGTP
ENNKEYAKVSGVMDNNILVLVPDPHAKNVACFEESAKEAPPSLEQNQAEKALANFTATSS
KCRLQLGGLDYLDPACFTHSFH
Number of residues622
Molecular Weight69505.045
Theoretical pI5.08
GO Classification
Functions
  • protein homodimerization activity
  • peptide hormone binding
  • ornithine decarboxylase activator activity
  • prolactin receptor activity
  • metal ion binding
Processes
  • embryo implantation
  • regulation of cell adhesion
  • JAK-STAT cascade involved in growth hormone signaling pathway
  • lactation
  • mammary gland epithelial cell differentiation
  • prostate gland growth
  • steroid biosynthetic process
  • regulation of epithelial cell differentiation
  • negative regulation of apoptotic process
  • cell surface receptor signaling pathway
  • mammary gland alveolus development
  • T cell activation
  • activation of JAK2 kinase activity
  • activation of transmembrane receptor protein tyrosine kinase activity
Components
  • cell surface
  • integral component of membrane
  • endosome lumen
  • extracellular region
  • plasma membrane
General FunctionProtein homodimerization activity
Specific FunctionThis is a receptor for the anterior pituitary hormone prolactin (PRL). Acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation through suppression of SRC kinase activation and stimulation of AKT. Isoform 4 is unable to transduce prolactin signaling. Isoform 6 is unable to transduce prolactin signaling.
Pfam Domain Function
Transmembrane Regions235-258
GenBank Protein ID190362
UniProtKB IDP16471
UniProtKB Entry NamePRLR_HUMAN
Cellular LocationMembrane
Gene sequence
>lcl|BSEQ0018944|Prolactin receptor (PRLR)
ATGAAGGAAAATGTGGCATCTGCAACCGTTTTCACTCTGCTACTTTTTCTCAACACCTGC
CTTCTGAATGGACAGTTACCTCCTGGAAAACCTGAGATCTTTAAATGTCGTTCTCCCAAT
AAGGAAACATTCACCTGCTGGTGGAGGCCTGGGACAGATGGAGGACTTCCTACCAATTAT
TCACTGACTTACCACAGGGAAGGAGAGACACTCATGCATGAATGTCCAGACTACATAACC
GGTGGCCCCAACTCCTGCCACTTTGGCAAGCAGTACACCTCCATGTGGAGGACATACATC
ATGATGGTCAATGCCACTAACCAGATGGGAAGCAGTTTCTCGGATGAACTTTATGTGGAC
GTGACTTACATAGTTCAGCCAGACCCTCCTTTGGAGCTGGCTGTGGAAGTAAAACAGCCA
GAAGACAGAAAACCCTACCTGTGGATTAAATGGTCTCCACCTACCCTGATTGACTTAAAA
ACTGGTTGGTTCACGCTCCTGTATGAAATTCGATTAAAACCCGAGAAAGCAGCTGAGTGG
GAGATCCATTTTGCTGGGCAGCAAACAGAGTTTAAGATTCTCAGCCTACATCCAGGACAG
AAATACCTTGTCCAGGTTCGCTGCAAACCAGACCATGGATACTGGAGTGCATGGAGTCCA
GCGACCTTCATTCAGATACCTAGTGACTTCACCATGAATGATACAACCGTGTGGATCTCT
GTGGCTGTCCTTTCTGCTGTCATCTGTTTGATTATTGTCTGGGCAGTGGCTTTGAAGGGC
TATAGCATGGTGACCTGCATCTTTCCGCCAGTTCCTGGGCCAAAAATAAAAGGATTTGAT
GCTCATCTGTTGGAGAAGGGCAAGTCTGAAGAACTACTGAGTGCCTTGGGATGCCAAGAC
TTTCCTCCCACTTCTGACTATGAGGACTTGCTGGTGGAGTATTTAGAAGTAGATGATAGT
GAGGACCAGCATCTAATGTCAGTCCATTCAAAAGAACACCCAAGTCAAGGTATGAAACCC
ACATACCTGGATCCTGACACTGACTCAGGCCGGGGGAGCTGTGACAGCCCTTCCCTTTTG
TCTGAAAAGTGTGAGGAACCCCAGGCCAATCCCTCCACATTCTATGATCCTGAGGTCATT
GAGAAGCCAGAGAATCCTGAAACAACCCACACCTGGGACCCCCAGTGCATAAGCATGGAA
GGCAAAATCCCCTATTTTCATGCTGGTGGATCCAAATGTTCAACATGGCCCTTACCACAG
CCCAGCCAGCACAACCCCAGATCCTCTTACCACAATATTACTGATGTGTGTGAGCTGGCT
GTGGGCCCTGCAGGTGCACCGGCCACTCTGTTGAATGAAGCAGGTAAAGATGCTTTAAAA
TCCTCTCAAACCATTAAGTCTAGAGAAGAGGGAAAGGCAACCCAGCAGAGGGAGGTAGAA
AGCTTCCATTCTGAGACTGACCAGGATACGCCCTGGCTGCTGCCCCAGGAGAAAACCCCC
TTTGGCTCCGCTAAACCCTTGGATTATGTGGAGATTCACAAGGTCAACAAAGATGGTGCA
TTATCATTGCTACCAAAACAGAGAGAGAACAGCGGCAAGCCCAAGAAGCCCGGGACTCCT
GAGAACAATAAGGAGTATGCCAAGGTGTCCGGGGTCATGGATAACAACATCCTGGTGTTG
GTGCCAGATCCACATGCTAAAAACGTGGCTTGCTTTGAAGAATCAGCCAAAGAGGCCCCA
CCATCACTTGAACAGAATCAAGCTGAGAAAGCCCTGGCCAACTTCACTGCAACATCAAGC
AAGTGCAGGCTCCAGCTGGGTGGTTTGGATTACCTGGATCCCGCATGTTTTACACACTCC
TTTCACTGA
GenBank Gene IDM31661
GeneCard IDNot Available
GenAtlas IDPRLR
HGNC IDHGNC:9446
Chromosome Location5
Locus5p14-p13
References
  1. Boutin JM, Edery M, Shirota M, Jolicoeur C, Lesueur L, Ali S, Gould D, Djiane J, Kelly PA: Identification of a cDNA encoding a long form of prolactin receptor in human hepatoma and breast cancer cells. Mol Endocrinol. 1989 Sep;3(9):1455-61. 2558309
  2. Kline JB, Roehrs H, Clevenger CV: Functional characterization of the intermediate isoform of the human prolactin receptor. J Biol Chem. 1999 Dec 10;274(50):35461-8. 10585417
  3. Hu ZZ, Zhuang L, Meng J, Leondires M, Dufau ML: The human prolactin receptor gene structure and alternative promoter utilization: the generic promoter hPIII and a novel human promoter hP(N). J Clin Endocrinol Metab. 1999 Mar;84(3):1153-6. 10084611
  4. Hu ZZ, Meng J, Dufau ML: Isolation and characterization of two novel forms of the human prolactin receptor generated by alternative splicing of a newly identified exon 11. J Biol Chem. 2001 Nov 2;276(44):41086-94. Epub 2001 Aug 22. 11518703
  5. Kline JB, Rycyzyn MA, Clevenger CV: Characterization of a novel and functional human prolactin receptor isoform (deltaS1PRLr) containing only one extracellular fibronectin-like domain. Mol Endocrinol. 2002 Oct;16(10):2310-22. 12351696
  6. Trott JF, Hovey RC, Koduri S, Vonderhaar BK: Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein. J Mol Endocrinol. 2003 Feb;30(1):31-47. 12580759
  7. Pujianto DA, Curry BJ, Aitken RJ: Prolactin exerts a prosurvival effect on human spermatozoa via mechanisms that involve the stimulation of Akt phosphorylation and suppression of caspase activation and capacitation. Endocrinology. 2010 Mar;151(3):1269-79. doi: 10.1210/en.2009-0964. Epub 2009 Dec 23. 20032052
  8. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. 14702039
  9. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. 15372022
  10. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  11. Fuh G, Wells JA: Prolactin receptor antagonists that inhibit the growth of breast cancer cell lines. J Biol Chem. 1995 Jun 2;270(22):13133-7. 7768908
  12. Miller SL, DeMaria JE, Freier DO, Riegel AM, Clevenger CV: Novel association of Vav2 and Nek3 modulates signaling through the human prolactin receptor. Mol Endocrinol. 2005 Apr;19(4):939-49. Epub 2004 Dec 23. 15618286
  13. Walsh ST, Kossiakoff AA: Crystal structure and site 1 binding energetics of human placental lactogen. J Mol Biol. 2006 May 5;358(3):773-84. Epub 2006 Mar 2. 16546209
  14. Lazzaro MA, Pepin D, Pescador N, Murphy BD, Vanderhyden BC, Picketts DJ: The imitation switch protein SNF2L regulates steroidogenic acute regulatory protein expression during terminal differentiation of ovarian granulosa cells. Mol Endocrinol. 2006 Oct;20(10):2406-17. Epub 2006 Jun 1. 16740656
  15. Bogorad RL, Courtillot C, Mestayer C, Bernichtein S, Harutyunyan L, Jomain JB, Bachelot A, Kuttenn F, Kelly PA, Goffin V, Touraine P: Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors. Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14533-8. doi: 10.1073/pnas.0800685105. Epub 2008 Sep 8. 18779591
  16. Newey PJ, Gorvin CM, Cleland SJ, Willberg CB, Bridge M, Azharuddin M, Drummond RS, van der Merwe PA, Klenerman P, Bountra C, Thakker RV: Mutant prolactin receptor and familial hyperprolactinemia. N Engl J Med. 2013 Nov 21;369(21):2012-20. doi: 10.1056/NEJMoa1307557. Epub 2013 Nov 6. 24195502
  17. Somers W, Ultsch M, De Vos AM, Kossiakoff AA: The X-ray structure of a growth hormone-prolactin receptor complex. Nature. 1994 Dec 1;372(6505):478-81. 7984244
  18. Svensson LA, Bondensgaard K, Norskov-Lauritsen L, Christensen L, Becker P, Andersen MD, Maltesen MJ, Rand KD, Breinholt J: Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor. J Biol Chem. 2008 Jul 4;283(27):19085-94. doi: 10.1074/jbc.M801202200. Epub 2008 May 8. 18467331