ID PRL_HUMAN Reviewed; 227 AA. AC P01236; Q15199; Q92996; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 13-FEB-2019, entry version 185. DE RecName: Full=Prolactin; DE Short=PRL; DE Flags: Precursor; GN Name=PRL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=6260780; RA Cooke N.E., Coit D., Shine J., Baxter J.D., Martial J.A.; RT "Human prolactin. cDNA structural analysis and evolutionary RT comparisons."; RL J. Biol. Chem. 256:4007-4016(1981). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6325171; RA Truong A.T., Duez C., Belayew A., Renard A., Pictet R.L., Bell G.I., RA Martial J.A.; RT "Isolation and characterization of the human prolactin gene."; RL EMBO J. 3:429-437(1984). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2050267; DOI=10.1016/0303-7207(91)90247-P; RA Hiraoka Y., Tatsumi K., Shiozawa M., Aiso S., Fukasawa T., Yasuda K., RA Miyai K.; RT "A placenta-specific 5'non-coding exon of human prolactin."; RL Mol. Cell. Endocrinol. 75:71-80(1991). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-227. RX PubMed=6146607; DOI=10.1093/oxfordjournals.jbchem.a134757; RA Takahashi H., Nabeshima Y., Nabeshima Y., Ogata K., Takeuchi S.; RT "Molecular cloning and nucleotide sequence of DNA complementary to RT human decidual prolactin mRNA."; RL J. Biochem. 95:1491-1499(1984). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-201. RC TISSUE=Mammary gland; RX PubMed=9266104; DOI=10.1023/A:1005879103367; RA Shaw-Bruha C.M., Pirrucello S.J., Shull J.D.; RT "Expression of the prolactin gene in normal and neoplastic human RT breast tissues and human mammary cell lines: promoter usage and RT alternative mRNA splicing."; RL Breast Cancer Res. Treat. 44:243-253(1997). RN [7] RP PROTEIN SEQUENCE OF 29-227. RX PubMed=925136; DOI=10.1210/jcem-45-5-1112; RA Shome B., Parlow A.F.; RT "Human pituitary prolactin (hPRL): the entire linear amino acid RT sequence."; RL J. Clin. Endocrinol. Metab. 45:1112-1115(1977). RN [8] RP PROTEIN SEQUENCE OF 29-53. RX PubMed=1126929; RA Jacobs J.W., Niall H.D.; RT "High sensitivity automated sequence determination of polypeptides."; RL J. Biol. Chem. 250:3629-3636(1975). RN [9] RP PHOSPHORYLATION AT SER-163 AND SER-194. RX PubMed=15687336; DOI=10.1210/jc.2004-1600; RA Hattori N., Ikekubo K., Nakaya Y., Kitagawa K., Inagaki C.; RT "Immunoglobulin G subclasses and prolactin (PRL) isoforms in RT macroprolactinemia due to anti-PRL autoantibodies."; RL J. Clin. Endocrinol. Metab. 90:3036-3044(2005). RN [10] RP STRUCTURE BY NMR OF 29-227. RX PubMed=12729745; DOI=10.1016/S0022-2836(03)00367-X; RA Keeler C., Dannies P.S., Hodsdon M.E.; RT "The tertiary structure and backbone dynamics of human prolactin."; RL J. Mol. Biol. 328:1105-1121(2003). RN [11] RP STRUCTURE BY NMR OF 29-227, AND INTERACTION WITH PRLR. RX PubMed=16045928; DOI=10.1016/j.jmb.2005.06.042; RA Teilum K., Hoch J.C., Goffin V., Kinet S., Martial J.A., RA Kragelund B.B.; RT "Solution structure of human prolactin."; RL J. Mol. Biol. 351:810-823(2005). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 38-227, AND MUTAGENESIS OF RP GLY-157. RX PubMed=17785459; DOI=10.1074/jbc.M704364200; RA Jomain J.-B., Tallet E., Broutin I., Hoos S., van Agthoven J., RA Ducruix A., Kelly P.A., Kragelund B.B., England P., Goffin V.; RT "Structural and thermodynamic bases for the design of pure prolactin RT receptor antagonists: X-ray structure of Del1-9-G129R-hPRL."; RL J. Biol. Chem. 282:33118-33131(2007). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 41-227 IN COMPLEX WITH PRLR, RP IDENTIFICATION BY MASS SPECTROMETRY, 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: Prolactin acts primarily on the mammary gland by CC promoting lactation. CC -!- SUBUNIT: Interacts with PRLR. {ECO:0000269|PubMed:16045928, CC ECO:0000269|PubMed:18467331}. CC -!- INTERACTION: CC P16471-1:PRLR; NbExp=2; IntAct=EBI-6903064, EBI-15968347; CC P16471-7:PRLR; NbExp=4; IntAct=EBI-6903064, EBI-6903057; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- SIMILARITY: Belongs to the somatotropin/prolactin family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA38264.1; Type=Frameshift; Positions=8; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Prolactin entry; CC URL="https://en.wikipedia.org/wiki/Prolactin"; 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; V00566; CAA23829.1; -; mRNA. DR EMBL; X00540; CAA25214.1; -; Genomic_DNA. DR EMBL; X00541; CAA25214.1; JOINED; Genomic_DNA. DR EMBL; X00543; CAA25214.1; JOINED; Genomic_DNA. DR EMBL; X00544; CAA25214.1; JOINED; Genomic_DNA. DR EMBL; X54393; CAA38263.1; ALT_FRAME; mRNA. DR EMBL; X54393; CAA38264.1; ALT_FRAME; mRNA. DR EMBL; BC015850; AAH15850.1; -; mRNA. DR EMBL; M29386; AAA60173.1; -; mRNA. DR EMBL; D00411; BAA00312.1; -; mRNA. DR EMBL; U75583; AAB70858.1; -; mRNA. DR CCDS; CCDS4548.1; -. DR PIR; A61402; A61402. DR PIR; A90998; LCHU. DR RefSeq; NP_000939.1; NM_000948.5. DR RefSeq; NP_001157030.1; NM_001163558.2. DR UniGene; Hs.1905; -. DR UniGene; Hs.735971; -. DR PDB; 1RW5; NMR; -; A=29-227. DR PDB; 2Q98; X-ray; 2.70 A; A=38-227. DR PDB; 3D48; X-ray; 2.50 A; P=40-227. DR PDB; 3EW3; X-ray; 3.80 A; A=39-227. DR PDB; 3MZG; X-ray; 2.10 A; A=43-227. DR PDB; 3N06; X-ray; 2.00 A; A=43-227. DR PDB; 3N0P; X-ray; 2.10 A; A=43-227. DR PDB; 3NCB; X-ray; 2.10 A; A=43-227. DR PDB; 3NCC; X-ray; 2.50 A; A=43-227. DR PDB; 3NCE; X-ray; 2.00 A; A=43-227. DR PDB; 3NCF; X-ray; 2.80 A; A=43-227. DR PDB; 3NPZ; X-ray; 3.35 A; A=29-227. DR PDBsum; 1RW5; -. DR PDBsum; 2Q98; -. DR PDBsum; 3D48; -. DR PDBsum; 3EW3; -. DR PDBsum; 3MZG; -. DR PDBsum; 3N06; -. DR PDBsum; 3N0P; -. DR PDBsum; 3NCB; -. DR PDBsum; 3NCC; -. DR PDBsum; 3NCE; -. DR PDBsum; 3NCF; -. DR PDBsum; 3NPZ; -. DR ProteinModelPortal; P01236; -. DR SMR; P01236; -. DR BioGrid; 111602; 3. DR CORUM; P01236; -. DR DIP; DIP-59635N; -. DR IntAct; P01236; 3. DR STRING; 9606.ENSP00000302150; -. DR iPTMnet; P01236; -. DR PhosphoSitePlus; P01236; -. DR BioMuta; PRL; -. DR PaxDb; P01236; -. DR PeptideAtlas; P01236; -. DR PRIDE; P01236; -. DR ProteomicsDB; 51352; -. DR DNASU; 5617; -. DR Ensembl; ENST00000306482; ENSP00000302150; ENSG00000172179. DR GeneID; 5617; -. DR KEGG; hsa:5617; -. DR CTD; 5617; -. DR DisGeNET; 5617; -. DR EuPathDB; HostDB:ENSG00000172179.11; -. DR GeneCards; PRL; -. DR HGNC; HGNC:9445; PRL. DR HPA; CAB023353; -. DR HPA; HPA042416; -. DR HPA; HPA062017; -. DR MIM; 176760; gene. DR neXtProt; NX_P01236; -. DR OpenTargets; ENSG00000172179; -. DR PharmGKB; PA33790; -. DR eggNOG; ENOG410II74; Eukaryota. DR eggNOG; ENOG410XU1S; LUCA. DR GeneTree; ENSGT00730000110805; -. DR HOGENOM; HOG000264241; -. DR HOVERGEN; HBG104895; -. DR InParanoid; P01236; -. DR KO; K05439; -. DR OrthoDB; 1290070at2759; -. DR PhylomeDB; P01236; -. DR TreeFam; TF332592; -. DR Reactome; R-HSA-1170546; Prolactin receptor signaling. DR Reactome; R-HSA-977225; Amyloid fiber formation. DR Reactome; R-HSA-982772; Growth hormone receptor signaling. DR SignaLink; P01236; -. DR SIGNOR; P01236; -. DR ChiTaRS; PRL; human. DR EvolutionaryTrace; P01236; -. DR GeneWiki; Prolactin; -. DR GenomeRNAi; 5617; -. DR PMAP-CutDB; P01236; -. DR PRO; PR:P01236; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; ENSG00000172179; Expressed in 101 organ(s), highest expression level in pituitary gland. DR ExpressionAtlas; P01236; baseline and differential. DR Genevisible; P01236; HS. DR GO; GO:0031904; C:endosome lumen; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005179; F:hormone activity; IBA:GO_Central. DR GO; GO:0005148; F:prolactin receptor binding; IBA:GO_Central. DR GO; GO:0008283; P:cell population proliferation; TAS:ProtInc. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0007565; P:female pregnancy; IBA:GO_Central. DR GO; GO:0060397; P:growth hormone receptor signaling pathway via JAK-STAT; TAS:Reactome. DR GO; GO:0007595; P:lactation; IEA:UniProtKB-KW. DR GO; GO:0030879; P:mammary gland development; IBA:GO_Central. DR GO; GO:0016525; P:negative regulation of angiogenesis; NAS:BHF-UCL. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:1903489; P:positive regulation of lactation; IBA:GO_Central. DR GO; GO:1902895; P:positive regulation of pri-miRNA transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0046427; P:positive regulation of receptor signaling pathway via JAK-STAT; IDA:BHF-UCL. DR GO; GO:0040014; P:regulation of multicellular organism growth; IEP:BHF-UCL. DR GO; GO:0031667; P:response to nutrient levels; IBA:GO_Central. DR InterPro; IPR009079; 4_helix_cytokine-like_core. DR InterPro; IPR001400; Somatotropin/Prolactin. DR InterPro; IPR018116; Somatotropin_CS. DR PANTHER; PTHR11417; PTHR11417; 1. DR Pfam; PF00103; Hormone_1; 1. DR PRINTS; PR00836; SOMATOTROPIN. DR SUPFAM; SSF47266; SSF47266; 1. DR PROSITE; PS00266; SOMATOTROPIN_1; 1. DR PROSITE; PS00338; SOMATOTROPIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Direct protein sequencing; KW Disulfide bond; Glycoprotein; Hormone; Lactation; Phosphoprotein; KW Reference proteome; Secreted; Signal. FT SIGNAL 1 28 {ECO:0000269|PubMed:1126929, FT ECO:0000269|PubMed:925136}. FT CHAIN 29 227 Prolactin. FT /FTId=PRO_0000032916. FT MOD_RES 54 54 Phosphoserine. FT {ECO:0000250|UniProtKB:P01239}. FT MOD_RES 62 62 Phosphoserine. FT {ECO:0000250|UniProtKB:P01239}. FT MOD_RES 118 118 Phosphoserine. FT {ECO:0000250|UniProtKB:P01239}. FT MOD_RES 163 163 Phosphoserine. FT {ECO:0000269|PubMed:15687336}. FT MOD_RES 194 194 Phosphoserine. FT {ECO:0000269|PubMed:15687336}. FT CARBOHYD 59 59 N-linked (GlcNAc...) asparagine; partial. FT DISULFID 32 39 {ECO:0000269|PubMed:18467331}. FT DISULFID 86 202 {ECO:0000269|PubMed:18467331}. FT DISULFID 219 227 {ECO:0000269|PubMed:18467331}. FT MUTAGEN 157 157 G->D,F,L,N,R,V,Y: Inhibits signaling via FT PRLR; mutant PRL acts as PRLR antagonist. FT {ECO:0000269|PubMed:17785459}. FT CONFLICT 42 42 T -> A (in Ref. 6; AAB70858). FT {ECO:0000305}. FT CONFLICT 110 111 SL -> VS (in Ref. 7; AA sequence). FT {ECO:0000305}. FT CONFLICT 113 114 VS -> L (in Ref. 7; AA sequence). FT {ECO:0000305}. FT CONFLICT 118 118 S -> P (in Ref. 6; AAB70858). FT {ECO:0000305}. FT CONFLICT 148 148 E -> Q (in Ref. 5; BAA00312). FT {ECO:0000305}. FT CONFLICT 172 172 N -> D (in Ref. 7; AA sequence). FT {ECO:0000305}. FT CONFLICT 190 191 ES -> SE (in Ref. 7; AA sequence). FT {ECO:0000305}. FT CONFLICT 206 206 D -> H (in Ref. 5; AAA60173/BAA00312). FT {ECO:0000305}. FT STRAND 31 34 {ECO:0000244|PDB:1RW5}. FT HELIX 43 72 {ECO:0000244|PDB:3N06}. FT TURN 73 75 {ECO:0000244|PDB:3N06}. FT HELIX 78 82 {ECO:0000244|PDB:3N06}. FT TURN 87 90 {ECO:0000244|PDB:3N06}. FT HELIX 97 102 {ECO:0000244|PDB:3N06}. FT HELIX 105 118 {ECO:0000244|PDB:3N06}. FT HELIX 120 131 {ECO:0000244|PDB:3N06}. FT STRAND 133 135 {ECO:0000244|PDB:3NCE}. FT HELIX 138 165 {ECO:0000244|PDB:3N06}. FT STRAND 166 168 {ECO:0000244|PDB:3NCC}. FT HELIX 181 185 {ECO:0000244|PDB:3N06}. FT HELIX 189 223 {ECO:0000244|PDB:3N06}. SQ SEQUENCE 227 AA; 25876 MW; 952BBA1B6A955527 CRC64; MNIKGSPWKG SLLLLLVSNL LLCQSVAPLP ICPGGAARCQ VTLRDLFDRA VVLSHYIHNL SSEMFSEFDK RYTHGRGFIT KAINSCHTSS LATPEDKEQA QQMNQKDFLS LIVSILRSWN EPLYHLVTEV RGMQEAPEAI LSKAVEIEEQ TKRLLEGMEL IVSQVHPETK ENEIYPVWSG LPSLQMADEE SRLSAYYNLL HCLRRDSHKI DNYLKLLKCR IIHNNNC //