Prolactin receptor

Details

Name

Prolactin receptor

Synonyms

• PRL-R

Gene Name

PRLR

UniProtKB Entry

P16471Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0000687|Prolactin receptor
MKENVASATVFTLLLFLNTCLLNGQLPPGKPEIFKCRSPNKETFTCWWRPGTDGGLPTNY
SLTYHREGETLMHECPDYITGGPNSCHFGKQYTSMWRTYIMMVNATNQMGSSFSDELYVD
VTYIVQPDPPLELAVEVKQPEDRKPYLWIKWSPPTLIDLKTGWFTLLYEIRLKPEKAAEW
EIHFAGQQTEFKILSLHPGQKYLVQVRCKPDHGYWSAWSPATFIQIPSDFTMNDTTVWIS
VAVLSAVICLIIVWAVALKGYSMVTCIFPPVPGPKIKGFDAHLLEKGKSEELLSALGCQD
FPPTSDYEDLLVEYLEVDDSEDQHLMSVHSKEHPSQGMKPTYLDPDTDSGRGSCDSPSLL
SEKCEEPQANPSTFYDPEVIEKPENPETTHTWDPQCISMEGKIPYFHAGGSKCSTWPLPQ
PSQHNPRSSYHNITDVCELAVGPAGAPATLLNEAGKDALKSSQTIKSREEGKATQQREVE
SFHSETDQDTPWLLPQEKTPFGSAKPLDYVEIHKVNKDGALSLLPKQRENSGKPKKPGTP
ENNKEYAKVSGVMDNNILVLVPDPHAKNVACFEESAKEAPPSLEQNQAEKALANFTATSS
KCRLQLGGLDYLDPACFTHSFH

Number of residues

622

Molecular Weight

69505.045

Theoretical pI

5.08

GO Classification

Functions

cytokine binding / lipid binding / protein kinase binding

Processes

activation of Janus kinase activity / cell surface receptor signaling pathway via JAK-STAT / cellular response to granulocyte macrophage colony-stimulating factor stimulus / cytokine-mediated signaling pathway / positive regulation of B cell proliferation / positive regulation of cell population proliferation / positive regulation of cold-induced thermogenesis / positive regulation of protein autophosphorylation / response to bacterium

Components

external side of plasma membrane / receptor complex

General Function

This 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

Specific Function

Cytokine binding

Pfam Domain Function

• EpoR_lig-bind (PF09067)

Signal Regions

1-24

Transmembrane Regions

235-258

Cellular Location

Membrane

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

Chromosome Location

5

Locus

5p13.2

External Identifiers

Resource	Link
UniProtKB ID	P16471
UniProtKB Entry Name	PRLR_HUMAN
GenBank Protein ID	190362
GenBank Gene ID	M31661
GeneCard ID	PRLR
GenAtlas ID	PRLR
HGNC ID	HGNC:9446
PDB ID(s)	1BP3, 2LFG, 2N7I, 3D48, 3MZG, 3N06, 3N0P, 3NCB, 3NCC, 3NCE, 3NCF, 4I18
KEGG ID	hsa:5618
NCBI Gene ID	5618

General 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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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Associated Data

Bio-Entities

Bio-Entity	Type
Prolactin receptor (Humans)	protein primary

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Somatotropin	approved, investigational	yes	target	ligand	Details
Lonapegsomatropin	approved, investigational	yes	target	ligand	Details