PRL_HUMAN
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 03-AUG-2022, entry version 203.
DE RecName: Full=Prolactin;
DE Short=PRL;
DE Flags: Precursor;
GN Name=PRL;
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].
RX PubMed=6260780; DOI=10.1016/s0021-9258(19)69558-x;
RA Cooke N.E., Coit D., Shine J., Baxter J.D., Martial J.A.;
RT "Human prolactin. cDNA structural analysis and evolutionary comparisons.";
RL J. Biol. Chem. 256:4007-4016(1981).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6325171; DOI=10.1002/j.1460-2075.1984.tb01824.x;
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 project:
RT 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 human
RT 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 breast
RT tissues and human mammary cell lines: promoter usage and alternative mRNA
RT 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 sequence.";
RL J. Clin. Endocrinol. Metab. 45:1112-1115(1977).
RN [8]
RP PROTEIN SEQUENCE OF 29-53.
RX PubMed=1126929; DOI=10.1016/s0021-9258(19)41443-9;
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., 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., Ducruix A.,
RA 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 promoting
CC lactation.
CC -!- SUBUNIT: Interacts with PRLR. {ECO:0000269|PubMed:16045928,
CC ECO:0000269|PubMed:18467331}.
CC -!- INTERACTION:
CC P01236; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-6903064, EBI-16439278;
CC P01236; P16471-1: PRLR; NbExp=2; IntAct=EBI-6903064, EBI-15968347;
CC P01236; 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; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Prolactin entry;
CC URL="https://en.wikipedia.org/wiki/Prolactin";
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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 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 AlphaFoldDB; P01236; -.
DR BMRB; P01236; -.
DR SMR; P01236; -.
DR BioGRID; 111602; 5.
DR CORUM; P01236; -.
DR DIP; DIP-59635N; -.
DR IntAct; P01236; 4.
DR STRING; 9606.ENSP00000302150; -.
DR GlyGen; P01236; 1 site.
DR iPTMnet; P01236; -.
DR PhosphoSitePlus; P01236; -.
DR BioMuta; PRL; -.
DR MassIVE; P01236; -.
DR PaxDb; P01236; -.
DR PeptideAtlas; P01236; -.
DR PRIDE; P01236; -.
DR ProteomicsDB; 51352; -.
DR Antibodypedia; 10502; 1599 antibodies from 43 providers.
DR DNASU; 5617; -.
DR Ensembl; ENST00000306482.2; ENSP00000302150.1; ENSG00000172179.13.
DR GeneID; 5617; -.
DR KEGG; hsa:5617; -.
DR MANE-Select; ENST00000306482.2; ENSP00000302150.1; NM_000948.6; NP_000939.1.
DR CTD; 5617; -.
DR DisGeNET; 5617; -.
DR GeneCards; PRL; -.
DR HGNC; HGNC:9445; PRL.
DR HPA; ENSG00000172179; Tissue enriched (pituitary).
DR MIM; 176760; gene.
DR neXtProt; NX_P01236; -.
DR OpenTargets; ENSG00000172179; -.
DR PharmGKB; PA33790; -.
DR VEuPathDB; HostDB:ENSG00000172179; -.
DR eggNOG; ENOG502QYU3; Eukaryota.
DR GeneTree; ENSGT00950000182818; -.
DR InParanoid; P01236; -.
DR PhylomeDB; P01236; -.
DR TreeFam; TF332592; -.
DR PathwayCommons; P01236; -.
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 BioGRID-ORCS; 5617; 6 hits in 1068 CRISPR screens.
DR ChiTaRS; PRL; human.
DR EvolutionaryTrace; P01236; -.
DR GeneWiki; Prolactin; -.
DR GenomeRNAi; 5617; -.
DR Pharos; P01236; Tbio.
DR PRO; PR:P01236; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P01236; protein.
DR Bgee; ENSG00000172179; Expressed in pituitary gland and 94 other tissues.
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:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007565; P:female pregnancy; IBA:GO_Central.
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 miRNA transcription; 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 Gene3D; 1.20.1250.10; -; 1.
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; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hormone; Lactation; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000269|PubMed:1126929,
FT ECO:0000269|PubMed:925136"
FT CHAIN 29..227
FT /note="Prolactin"
FT /id="PRO_0000032916"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01239"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01239"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P01239"
FT MOD_RES 163
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15687336"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15687336"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT DISULFID 32..39
FT /evidence="ECO:0000269|PubMed:18467331"
FT DISULFID 86..202
FT /evidence="ECO:0000269|PubMed:18467331"
FT DISULFID 219..227
FT /evidence="ECO:0000269|PubMed:18467331"
FT MUTAGEN 157
FT /note="G->D,F,L,N,R,V,Y: Inhibits signaling via PRLR;
FT mutant PRL acts as PRLR antagonist."
FT /evidence="ECO:0000269|PubMed:17785459"
FT CONFLICT 42
FT /note="T -> A (in Ref. 6; AAB70858)"
FT /evidence="ECO:0000305"
FT CONFLICT 110..111
FT /note="SL -> VS (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 113..114
FT /note="VS -> L (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="S -> P (in Ref. 6; AAB70858)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="E -> Q (in Ref. 5; BAA00312)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="N -> D (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 190..191
FT /note="ES -> SE (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="D -> H (in Ref. 5; AAA60173/BAA00312)"
FT /evidence="ECO:0000305"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:1RW5"
FT HELIX 43..72
FT /evidence="ECO:0007829|PDB:3N06"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:3N06"
FT HELIX 78..82
FT /evidence="ECO:0007829|PDB:3N06"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:3N06"
FT HELIX 97..102
FT /evidence="ECO:0007829|PDB:3N06"
FT HELIX 105..118
FT /evidence="ECO:0007829|PDB:3N06"
FT HELIX 120..131
FT /evidence="ECO:0007829|PDB:3N06"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:3NCE"
FT HELIX 138..165
FT /evidence="ECO:0007829|PDB:3N06"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:3NCC"
FT HELIX 181..185
FT /evidence="ECO:0007829|PDB:3N06"
FT HELIX 189..223
FT /evidence="ECO:0007829|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
