UniProtKB - P16471 (PRLR_HUMAN)
Prolactin receptor
PRLR
Functioni
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.
2 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 211 | Zinc | 1 | |
Metal bindingi | 212 | Zinc | 1 |
GO - Molecular functioni
- ciliary neurotrophic factor receptor binding Source: GO_Central
- cytokine binding Source: GO_Central
- cytokine receptor activity Source: GO_Central
- leukemia inhibitory factor receptor activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- peptide hormone binding Source: BHF-UCL
- prolactin receptor activity Source: UniProtKB
- protein kinase binding Source: Ensembl
GO - Biological processi
- activation of Janus kinase activity Source: UniProtKB
- activation of transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
- cytokine-mediated signaling pathway Source: GO_Central
- embryo implantation Source: ProtInc
- lactation Source: ProtInc
- mammary gland alveolus development Source: Ensembl
- mammary gland epithelial cell differentiation Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKB
- oncostatin-M-mediated signaling pathway Source: GOC
- positive regulation of cell population proliferation Source: GO_Central
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- prostate gland growth Source: Ensembl
- receptor signaling pathway via JAK-STAT Source: Ensembl
- regulation of cell adhesion Source: Ensembl
- regulation of epithelial cell differentiation Source: Ensembl
- response to bacterium Source: Ensembl
- steroid biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Receptor |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | P16471 |
Reactomei | R-HSA-1170546, Prolactin receptor signaling R-HSA-982772, Growth hormone receptor signaling |
SignaLinki | P16471 |
SIGNORi | P16471 |
Names & Taxonomyi
Protein namesi | Recommended name: Prolactin receptorShort name: PRL-R |
Gene namesi | Name:PRLR |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9446, PRLR |
MIMi | 176761, gene |
neXtProti | NX_P16471 |
VEuPathDBi | HostDB:ENSG00000113494 |
Subcellular locationi
Other locations
- Membrane 2 Publications; Single-pass type I membrane protein 2 Publications
Extracellular region or secreted
Endosome
- endosome lumen Source: Reactome
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Plasma Membrane
- external side of plasma membrane Source: GO_Central
- plasma membrane Source: Reactome
Other locations
- cell surface Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
- receptor complex Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 25 – 234 | ExtracellularSequence analysisAdd BLAST | 210 | |
Transmembranei | 235 – 258 | HelicalSequence analysisAdd BLAST | 24 | |
Topological domaini | 259 – 622 | CytoplasmicSequence analysisAdd BLAST | 364 |
Keywords - Cellular componenti
Membrane, SecretedPathology & Biotechi
Involvement in diseasei
Multiple fibroadenomas of the breast (MFAB)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070894 | 170 | I → L in MFAB; confers constitutive activity. 1 PublicationCorresponds to variant dbSNP:rs72478580EnsemblClinVar. | 1 |
Hyperprolactinemia (HPRL)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070895 | 212 | H → R in HPRL; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398122522EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 5618 |
MalaCardsi | PRLR |
MIMi | 615554, phenotype 615555, phenotype |
OpenTargetsi | ENSG00000113494 |
Orphaneti | 397685, Familial hyperprolactinemia |
PharmGKBi | PA33791 |
Miscellaneous databases
Pharosi | P16471, Tbio |
Chemistry databases
ChEMBLi | CHEMBL5588 |
DrugBanki | DB16220, Lonapegsomatropin DB00052, Somatotropin |
Genetic variation databases
BioMutai | PRLR |
DMDMi | 130321 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | Add BLAST | 24 | |
ChainiPRO_0000010977 | 25 – 622 | Prolactin receptorAdd BLAST | 598 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 36 ↔ 46 | 1 Publication | ||
Glycosylationi | 59 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 75 ↔ 86 | 1 Publication | ||
Glycosylationi | 104 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 233 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MassIVEi | P16471 |
PaxDbi | P16471 |
PeptideAtlasi | P16471 |
PRIDEi | P16471 |
ProteomicsDBi | 12725 53366 [P16471-1] 53367 [P16471-2] 53368 [P16471-3] 53369 [P16471-4] 53370 [P16471-5] 53371 [P16471-6] 53372 [P16471-7] 53373 [P16471-8] |
PTM databases
GlyGeni | P16471, 3 sites |
iPTMneti | P16471 |
PhosphoSitePlusi | P16471 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000113494, Expressed in placenta and 165 other tissues |
ExpressionAtlasi | P16471, baseline and differential |
Genevisiblei | P16471, HS |
Organism-specific databases
HPAi | ENSG00000113494, Tissue enriched (choroid) |
Interactioni
Subunit structurei
Homodimer upon hormone binding.
Interacts with SMARCA1.
Interacts with GH1.
Interacts with CSH.
Interacts with NEK3 and VAV2 and this interaction is prolactin-dependent.
5 PublicationsBinary interactionsi
P16471
With | #Exp. | IntAct |
---|---|---|
INSIG2 [Q9Y5U4] | 3 | EBI-476182,EBI-8503746 |
PLPP6 [Q8IY26] | 3 | EBI-476182,EBI-11721828 |
YWHAZ [P63104] | 3 | EBI-476182,EBI-347088 |
Isoform 1 [P16471-1]
With | #Exp. | IntAct |
---|---|---|
PRL [P01236] | 2 | EBI-15968347,EBI-6903064 |
Isoform 7 [P16471-7]
With | #Exp. | IntAct |
---|---|---|
PRL [P01236] | 4 | EBI-6903057,EBI-6903064 |
GO - Molecular functioni
- ciliary neurotrophic factor receptor binding Source: GO_Central
- cytokine binding Source: GO_Central
- protein kinase binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 111603, 17 interactors |
CORUMi | P16471 |
DIPi | DIP-288N |
ELMi | P16471 |
IntActi | P16471, 8 interactors |
MINTi | P16471 |
STRINGi | 9606.ENSP00000482954 |
Chemistry databases
BindingDBi | P16471 |
Miscellaneous databases
RNActi | P16471, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P16471 |
BMRBi | P16471 |
SMRi | P16471 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P16471 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 27 – 128 | Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST | 102 | |
Domaini | 129 – 229 | Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST | 101 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 326 – 378 | DisorderedSequence analysisAdd BLAST | 53 | |
Regioni | 461 – 505 | DisorderedSequence analysisAdd BLAST | 45 | |
Regioni | 520 – 545 | DisorderedSequence analysisAdd BLAST | 26 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 215 – 219 | WSXWS motif | 5 | |
Motifi | 267 – 275 | Box 1 motif | 9 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 462 – 485 | Basic and acidic residuesSequence analysisAdd BLAST | 24 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502R22A, Eukaryota |
GeneTreei | ENSGT00940000154851 |
HOGENOMi | CLU_017892_1_0_1 |
InParanoidi | P16471 |
OMAi | YHYELRL |
OrthoDBi | 346239at2759 |
PhylomeDBi | P16471 |
TreeFami | TF330851 |
Family and domain databases
CDDi | cd00063, FN3, 2 hits |
DisProti | DP01106 |
Gene3Di | 2.60.40.10, 2 hits |
InterProi | View protein in InterPro IPR003961, FN3_dom IPR036116, FN3_sf IPR015152, Growth/epo_recpt_lig-bind IPR013783, Ig-like_fold IPR003528, Long_hematopoietin_rcpt_CS IPR033230, PRLR |
PANTHERi | PTHR23036:SF86, PTHR23036:SF86, 2 hits |
Pfami | View protein in Pfam PF09067, EpoR_lig-bind, 1 hit |
SMARTi | View protein in SMART SM00060, FN3, 2 hits |
SUPFAMi | SSF49265, SSF49265, 2 hits |
PROSITEi | View protein in PROSITE PS50853, FN3, 2 hits PS01352, HEMATOPO_REC_L_F1, 1 hit |
s (9+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 9 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 9 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKENVASATV FTLLLFLNTC LLNGQLPPGK PEIFKCRSPN KETFTCWWRP
60 70 80 90 100
GTDGGLPTNY SLTYHREGET LMHECPDYIT GGPNSCHFGK QYTSMWRTYI
110 120 130 140 150
MMVNATNQMG SSFSDELYVD VTYIVQPDPP LELAVEVKQP EDRKPYLWIK
160 170 180 190 200
WSPPTLIDLK TGWFTLLYEI RLKPEKAAEW EIHFAGQQTE FKILSLHPGQ
210 220 230 240 250
KYLVQVRCKP DHGYWSAWSP ATFIQIPSDF TMNDTTVWIS VAVLSAVICL
260 270 280 290 300
IIVWAVALKG YSMVTCIFPP VPGPKIKGFD AHLLEKGKSE ELLSALGCQD
310 320 330 340 350
FPPTSDYEDL LVEYLEVDDS EDQHLMSVHS KEHPSQGMKP TYLDPDTDSG
360 370 380 390 400
RGSCDSPSLL SEKCEEPQAN PSTFYDPEVI EKPENPETTH TWDPQCISME
410 420 430 440 450
GKIPYFHAGG SKCSTWPLPQ PSQHNPRSSY HNITDVCELA VGPAGAPATL
460 470 480 490 500
LNEAGKDALK SSQTIKSREE GKATQQREVE SFHSETDQDT PWLLPQEKTP
510 520 530 540 550
FGSAKPLDYV EIHKVNKDGA LSLLPKQREN SGKPKKPGTP ENNKEYAKVS
560 570 580 590 600
GVMDNNILVL VPDPHAKNVA CFEESAKEAP PSLEQNQAEK ALANFTATSS
610 620
KCRLQLGGLD YLDPACFTHS FH
The sequence of this isoform differs from the canonical sequence as follows:
338-376: MKPTYLDPDT...PQANPSTFYD → DPLMLGASHY...FTKATLTTVQ
377-622: Missing.
The sequence of this isoform differs from the canonical sequence as follows:
1-71: Missing.
286-288: KGK → VTP
289-622: Missing.
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketD6RC67 | D6RC67_HUMAN | Prolactin receptor | PRLR | 102 | Annotation score: | ||
D6RD41 | D6RD41_HUMAN | Prolactin receptor | PRLR | 111 | Annotation score: | ||
D6R9P5 | D6R9P5_HUMAN | Prolactin receptor | PRLR | 120 | Annotation score: | ||
D6R9V7 | D6R9V7_HUMAN | Prolactin receptor | PRLR | 62 | Annotation score: | ||
D6RAN9 | D6RAN9_HUMAN | Prolactin receptor | PRLR | 34 | Annotation score: | ||
D6RJC8 | D6RJC8_HUMAN | Prolactin receptor | PRLR | 33 | Annotation score: | ||
D6R9E1 | D6R9E1_HUMAN | Prolactin receptor | PRLR | 34 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_049172 | 100 | I → V. Corresponds to variant dbSNP:rs2228482Ensembl. | 1 | |
Natural variantiVAR_070894 | 170 | I → L in MFAB; confers constitutive activity. 1 PublicationCorresponds to variant dbSNP:rs72478580EnsemblClinVar. | 1 | |
Natural variantiVAR_070895 | 212 | H → R in HPRL; loss of function. 1 PublicationCorresponds to variant dbSNP:rs398122522EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_026531 | 1 – 71 | Missing in isoform 8. 1 PublicationAdd BLAST | 71 | |
Alternative sequenceiVSP_001720 | 24 – 124 | Missing in isoform 2. 1 PublicationAdd BLAST | 101 | |
Alternative sequenceiVSP_026532 | 229 – 268 | DFTMN…VTCIF → GDPLMLGASHYKNLKSYRPR KISSQGRLAVFTKATLTTVQ in isoform 7. 1 PublicationAdd BLAST | 40 | |
Alternative sequenceiVSP_012620 | 229 – 230 | DF → AW in isoform 3. 1 Publication | 2 | |
Alternative sequenceiVSP_012621 | 231 – 622 | Missing in isoform 3. 1 PublicationAdd BLAST | 392 | |
Alternative sequenceiVSP_026533 | 269 – 622 | Missing in isoform 7. 1 PublicationAdd BLAST | 354 | |
Alternative sequenceiVSP_047882 | 286 – 309 | KGKSE…SDYED → DRLCTPGRCCVSTGLTDLDY SCST in isoform 9. 1 PublicationAdd BLAST | 24 | |
Alternative sequenceiVSP_026534 | 286 – 288 | KGK → VTP in isoform 6 and isoform 8. 2 Publications | 3 | |
Alternative sequenceiVSP_026535 | 289 – 622 | Missing in isoform 6 and isoform 8. 2 PublicationsAdd BLAST | 334 | |
Alternative sequenceiVSP_047883 | 310 – 622 | Missing in isoform 9. 1 PublicationAdd BLAST | 313 | |
Alternative sequenceiVSP_026536 | 337 – 349 | GMKPT…PDTDS → EREQRQAQEARDS in isoform 5. 1 PublicationAdd BLAST | 13 | |
Alternative sequenceiVSP_026537 | 338 – 376 | MKPTY…STFYD → DPLMLGASHYKNLKSYRPRK ISSQGRLAVFTKATLTTVQ in isoform 4. 2 PublicationsAdd BLAST | 39 | |
Alternative sequenceiVSP_026538 | 350 – 622 | Missing in isoform 5. 1 PublicationAdd BLAST | 273 | |
Alternative sequenceiVSP_026539 | 377 – 622 | Missing in isoform 4. 2 PublicationsAdd BLAST | 246 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BP3 | X-ray | 2.90 | B | 25-235 | [»] | |
2LFG | NMR | - | A | 123-234 | [»] | |
2N7I | NMR | - | A | 230-264 | [»] | |
3D48 | X-ray | 2.50 | R | 25-234 | [»] | |
3MZG | X-ray | 2.10 | B | 26-234 | [»] | |
3N06 | X-ray | 2.00 | B | 26-234 | [»] | |
3N0P | X-ray | 2.10 | B | 26-234 | [»] | |
3NCB | X-ray | 2.10 | B | 26-234 | [»] | |
3NCC | X-ray | 2.50 | B | 26-234 | [»] | |
3NCE | X-ray | 2.00 | B | 26-234 | [»] | |
3NCF | X-ray | 2.80 | B | 26-234 | [»] | |
4I18 | X-ray | 3.24 | C/R | 25-235 | [»] | |
AlphaFoldDBi | P16471 | |||||
BMRBi | P16471 | |||||
SMRi | P16471 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111603, 17 interactors |
CORUMi | P16471 |
DIPi | DIP-288N |
ELMi | P16471 |
IntActi | P16471, 8 interactors |
MINTi | P16471 |
STRINGi | 9606.ENSP00000482954 |
Chemistry databases
BindingDBi | P16471 |
ChEMBLi | CHEMBL5588 |
DrugBanki | DB16220, Lonapegsomatropin DB00052, Somatotropin |
PTM databases
GlyGeni | P16471, 3 sites |
iPTMneti | P16471 |
PhosphoSitePlusi | P16471 |
Genetic variation databases
BioMutai | PRLR |
DMDMi | 130321 |
Proteomic databases
MassIVEi | P16471 |
PaxDbi | P16471 |
PeptideAtlasi | P16471 |
PRIDEi | P16471 |
ProteomicsDBi | 12725 53366 [P16471-1] 53367 [P16471-2] 53368 [P16471-3] 53369 [P16471-4] 53370 [P16471-5] 53371 [P16471-6] 53372 [P16471-7] 53373 [P16471-8] |
Protocols and materials databases
ABCDi | P16471, 42 sequenced antibodies |
Antibodypediai | 10116, 938 antibodies from 37 providers |
DNASUi | 5618 |
Genome annotation databases
Organism-specific databases
CTDi | 5618 |
DisGeNETi | 5618 |
GeneCardsi | PRLR |
HGNCi | HGNC:9446, PRLR |
HPAi | ENSG00000113494, Tissue enriched (choroid) |
MalaCardsi | PRLR |
MIMi | 176761, gene 615554, phenotype 615555, phenotype |
neXtProti | NX_P16471 |
OpenTargetsi | ENSG00000113494 |
Orphaneti | 397685, Familial hyperprolactinemia |
PharmGKBi | PA33791 |
VEuPathDBi | HostDB:ENSG00000113494 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502R22A, Eukaryota |
GeneTreei | ENSGT00940000154851 |
HOGENOMi | CLU_017892_1_0_1 |
InParanoidi | P16471 |
OMAi | YHYELRL |
OrthoDBi | 346239at2759 |
PhylomeDBi | P16471 |
TreeFami | TF330851 |
Enzyme and pathway databases
PathwayCommonsi | P16471 |
Reactomei | R-HSA-1170546, Prolactin receptor signaling R-HSA-982772, Growth hormone receptor signaling |
SignaLinki | P16471 |
SIGNORi | P16471 |
Miscellaneous databases
BioGRID-ORCSi | 5618, 8 hits in 1072 CRISPR screens |
ChiTaRSi | PRLR, human |
EvolutionaryTracei | P16471 |
GenomeRNAii | 5618 |
Pharosi | P16471, Tbio |
PROi | PR:P16471 |
RNActi | P16471, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000113494, Expressed in placenta and 165 other tissues |
ExpressionAtlasi | P16471, baseline and differential |
Genevisiblei | P16471, HS |
Family and domain databases
CDDi | cd00063, FN3, 2 hits |
DisProti | DP01106 |
Gene3Di | 2.60.40.10, 2 hits |
InterProi | View protein in InterPro IPR003961, FN3_dom IPR036116, FN3_sf IPR015152, Growth/epo_recpt_lig-bind IPR013783, Ig-like_fold IPR003528, Long_hematopoietin_rcpt_CS IPR033230, PRLR |
PANTHERi | PTHR23036:SF86, PTHR23036:SF86, 2 hits |
Pfami | View protein in Pfam PF09067, EpoR_lig-bind, 1 hit |
SMARTi | View protein in SMART SM00060, FN3, 2 hits |
SUPFAMi | SSF49265, SSF49265, 2 hits |
PROSITEi | View protein in PROSITE PS50853, FN3, 2 hits PS01352, HEMATOPO_REC_L_F1, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PRLR_HUMAN | |
Accessioni | P16471Primary (citable) accession number: P16471 Secondary accession number(s): B2R882 Q9UHJ5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | August 1, 1990 | |
Last modified: | May 25, 2022 | |
This is version 229 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families