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   02-SEP-2026, entry version 221.
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_000948.6.
DR   RefSeq; NP_001157030.1; NM_001163558.3.
DR   RefSeq; XP_047275032.1; XM_047419076.1.
DR   RefSeq; XP_054211907.1; XM_054355932.1.
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=30-227.
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   AlphaFoldDB; P01236; -.
DR   BMRB; P01236; -.
DR   SMR; P01236; -.
DR   BioGRID; 111602; 7.
DR   DIP; DIP-59635N; -.
DR   FunCoup; P01236; 1066.
DR   IntAct; P01236; 4.
DR   NDEx; IQUERY-CP-PRL; 14 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000302150; -.
DR   GlyCosmos; P01236; 1 site, No reported glycans.
DR   GlyGen; P01236; 1 site.
DR   iPTMnet; P01236; -.
DR   PhosphoSitePlus; P01236; -.
DR   BioMuta; PRL; -.
DR   MassIVE; P01236; -.
DR   PaxDb; 9606-ENSP00000302150; -.
DR   PeptideAtlas; P01236; -.
DR   ProteomicsDB; 51352; -.
DR   Antibodypedia; 10502; 1695 antibodies from 48 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   AGR; HGNC:9445; -.
DR   ClinPGx; PA33790; -.
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   OpenTargets; ENSG00000172179; -.
DR   VEuPathDB; HostDB:ENSG00000172179; -.
DR   eggNOG; ENOG502QYU3; Eukaryota.
DR   GeneTree; ENSGT00950000182818; -.
DR   InParanoid; P01236; -.
DR   OrthoDB; 9946219at2759; -.
DR   PAN-GO; P01236; 9 GO annotations based on evolutionary models.
DR   PhylomeDB; P01236; -.
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   Reactome; R-HSA-9927426; Developmental Lineage of Mammary Gland Alveolar Cells.
DR   SignaLink; P01236; -.
DR   SIGNOR; P01236; -.
DR   Agora; ENSG00000172179; -.
DR   BioGRID-ORCS; 5617; 7 hits in 1140 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 96 other cell types or tissues.
DR   ExpressionAtlas; P01236; baseline and differential.
DR   GO; GO:0031904; C:endosome lumen; TAS:Reactome.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
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; IBA:GO_Central.
DR   GO; GO:0007565; P:female pregnancy; IBA:GO_Central.
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:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:BHF-UCL.
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:0038161; P:prolactin signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0031667; P:response to nutrient levels; IBA:GO_Central.
DR   CDD; cd10288; prolactin_like; 1.
DR   FunFam; 1.20.1250.10:FF:000003; Prolactin; 1.
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:SF5; PROLACTIN; 1.
DR   PANTHER; PTHR11417; SOMATOTROPIN,PROLACTIN; 1.
DR   Pfam; PF00103; Hormone_1; 1.
DR   PRINTS; PR00836; SOMATOTROPIN.
DR   SUPFAM; SSF47266; 4-helical cytokines; 1.
DR   PROSITE; PS00266; SOMATOTROPIN_1; 1.
DR   PROSITE; PS00338; SOMATOTROPIN_2; 1.
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; -.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Hormone; Lactation; Phosphoprotein; Proteomics identification;
KW   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 a 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           176..178
FT                   /evidence="ECO:0007829|PDB:3N06"
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
//