PRLR

Protein identityUniProt · HPA

UniProt accession

P16471

Gene

PRLR

Ensembl

ENSG00000113494

Chromosome

5

Canonical length

622 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a receptor for the anterior pituitary hormone, prolactin, and belongs to the type I cytokine receptor family. Prolactin-dependent signaling occurs as the result of ligand-induced dimerization of the prolactin receptor. Several alternatively spliced transcript variants encoding different membrane-bound and soluble isoforms have been described for this gene, which may function to modulate the endocrine and autocrine effects of prolactin in normal tissue and cancer. [provided by RefSeq, Feb 2011]

Canonical amino-acid sequenceUniProt

622 residues, UniProt reviewed canonical sequence.

>P16471|PRLR
     1  MKENVASATV FTLLLFLNTC LLNGQLPPGK PEIFKCRSPN KETFTCWWRP GTDGGLPTNY
    61  SLTYHREGET LMHECPDYIT GGPNSCHFGK QYTSMWRTYI MMVNATNQMG SSFSDELYVD
   121  VTYIVQPDPP LELAVEVKQP EDRKPYLWIK WSPPTLIDLK TGWFTLLYEI RLKPEKAAEW
   181  EIHFAGQQTE FKILSLHPGQ KYLVQVRCKP DHGYWSAWSP ATFIQIPSDF TMNDTTVWIS
   241  VAVLSAVICL IIVWAVALKG YSMVTCIFPP VPGPKIKGFD AHLLEKGKSE ELLSALGCQD
   301  FPPTSDYEDL LVEYLEVDDS EDQHLMSVHS KEHPSQGMKP TYLDPDTDSG RGSCDSPSLL
   361  SEKCEEPQAN PSTFYDPEVI EKPENPETTH TWDPQCISME GKIPYFHAGG SKCSTWPLPQ
   421  PSQHNPRSSY HNITDVCELA VGPAGAPATL LNEAGKDALK SSQTIKSREE GKATQQREVE
   481  SFHSETDQDT PWLLPQEKTP FGSAKPLDYV EIHKVNKDGA LSLLPKQREN SGKPKKPGTP
   541  ENNKEYAKVS GVMDNNILVL VPDPHAKNVA CFEESAKEAP PSLEQNQAEK ALANFTATSS
   601  KCRLQLGGLD YLDPACFTHS FH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PRLR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.54

Highest tissue expression

121 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PRLR.

Disease | AllUniProt

Conditions PRLR is implicated in, by any mechanism.

• Multiple fibroadenomas of the breast (MFAB) MIM:615554
• Hyperprolactinemia (HPRL) MIM:615555

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 94 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial hyperprolactinemia
• Premature ovarian failure

ReferencesPubMed · IEDB

Publications for PRLR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.29

gnomAD pLI

0.99

gnomAD missense Z

0.68

DepMap mean gene effect

0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of Janus kinase activity
• activation of transmembrane receptor protein tyrosine kinase activity
• cell surface receptor signaling pathway via JAK-STAT
• cellular response to granulocyte macrophage colony-stimulating factor stimulus
• cytokine-mediated signaling pathway
• embryo implantation
• lactation
• mammary gland alveolus development
• mammary gland epithelial cell differentiation
• negative regulation of apoptotic process
• positive regulation of B cell proliferation
• positive regulation of cell population proliferation
• positive regulation of cold-induced thermogenesis
• prostate gland growth
• regulation of cell adhesion
• regulation of epithelial cell differentiation
• response to bacterium
• steroid biosynthetic process

Molecular functions

• cytokine binding
• lipid binding
• metal ion binding
• peptide hormone binding
• prolactin receptor activity
• protein kinase binding

Cellular components

• cell surface
• endosome lumen
• external side of plasma membrane
• extracellular region
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Long hematopoietin receptor, single chain, conserved site
• Fibronectin type III
• Immunoglobulin-like fold
• Growth hormone/erythropoietin receptor, ligand binding
• Fibronectin type III superfamily
• Type I Cytokine Receptor
• Erythropoietin receptor, ligand binding

KeywordsUniProt

• Disulfide bond
• Glycoprotein
• Membrane
• Metal-binding
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix
• Zinc

InteractionsUniProt · HPA

Protein binding partners of PRLR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CSH
• GH1
• NEK3
• SMARCA1
• VAV2
• PRL