UniProtKB - O00264 (PGRC1_HUMAN)
Protein
Membrane-associated progesterone receptor component 1
Gene
PGRMC1
Organism
Homo sapiens (Human)
Status
Functioni
Component of a progesterone-binding protein complex (PubMed:28396637). Binds progesterone (PubMed:25675345). Has many reported cellular functions (heme homeostasis, interaction with CYPs). Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan (By similarity). Intracellular heme chaperone. Regulates heme synthesis via interactions with FECH and acts as a heme donor for at least some hemoproteins (PubMed:27599036).1 PublicationBy similarity2 Publications
Miscellaneous
Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).2 Publications
Caution
Was initially identified as sigma-2 receptor, which is thought to play important role in regulating cell survival, morphology and differentiation (PubMed:21730960, PubMed:22292588, PubMed:28007569). However, it was later shown that it is not the case (PubMed:28007569). The sigma-2 receptor has been identified as TMEM97 (AC Q5BJF2) (PubMed:28559337).4 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 113 | Iron (heme axial ligand)Combined sources1 Publication | 1 |
GO - Molecular functioni
- amyloid-beta binding Source: ARUK-UCL
- heme binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- protein homodimerization activity Source: UniProtKB
- steroid binding Source: ProtInc
GO - Biological processi
- heme biosynthetic process Source: UniProtKB
- neutrophil degranulation Source: Reactome
Keywordsi
Molecular function | Receptor |
Ligand | Iron, Lipid-binding, Metal-binding, Steroid-binding |
Enzyme and pathway databases
PathwayCommonsi | O00264 |
Reactomei | R-HSA-6798695, Neutrophil degranulation |
Names & Taxonomyi
Protein namesi | Recommended name: Membrane-associated progesterone receptor component 1Short name: mPR Alternative name(s): Dap11 Publication IZA1 Publication |
Gene namesi | |
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:16090, PGRMC1 |
MIMi | 300435, gene |
neXtProti | NX_O00264 |
VEuPathDBi | HostDB:ENSG00000101856.9 |
Subcellular locationi
Mitochondrion
- Mitochondrion outer membrane By similarity; Single-pass membrane protein Curated; Extracellular side By similarity
Endoplasmic reticulum
- Microsome membrane By similarity; Single-pass membrane protein Sequence analysis
- Smooth endoplasmic reticulum membrane 1 Publication; Single-pass membrane protein Sequence analysis
Endoplasmic reticulum
- endoplasmic reticulum Source: ARUK-UCL
- smooth endoplasmic reticulum membrane Source: UniProtKB-SubCell
Mitochondrion
- mitochondrial outer membrane Source: UniProtKB
Plasma Membrane
- integral component of plasma membrane Source: ARUK-UCL
- plasma membrane Source: Reactome
Other locations
- cell body Source: ARUK-UCL
- endomembrane system Source: GO_Central
- membrane Source: UniProtKB
- neuron projection Source: ARUK-UCL
- neuronal cell body Source: ARUK-UCL
- specific granule membrane Source: Reactome
- synapse Source: ARUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 24 | LumenalSequence analysisAdd BLAST | 24 | |
Transmembranei | 25 – 43 | HelicalSequence analysisAdd BLAST | 19 | |
Topological domaini | 44 – 195 | CytoplasmicSequence analysisAdd BLAST | 152 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, Microsome, Mitochondrion, Mitochondrion outer membranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 113 | Y → F: Abolishes interaction with CYP1A1 and CYP3A4. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 10857 |
OpenTargetsi | ENSG00000101856 |
Orphaneti | 619, NON RARE IN EUROPE: Primary ovarian failure |
PharmGKBi | PA33248 |
Miscellaneous databases
Pharosi | O00264, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4105706 |
DrugBanki | DB00514, Dextromethorphan DB00540, Nortriptyline DB01104, Sertraline |
Genetic variation databases
BioMutai | PGRMC1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000121739 | 1 – 195 | Membrane-associated progesterone receptor component 1Add BLAST | 195 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 54 | PhosphoserineCombined sources | 1 | |
Modified residuei | 57 | PhosphoserineCombined sources | 1 | |
Modified residuei | 74 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 181 | PhosphoserineCombined sources1 Publication | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O00264 |
jPOSTi | O00264 |
MassIVEi | O00264 |
PaxDbi | O00264 |
PeptideAtlasi | O00264 |
PRIDEi | O00264 |
ProteomicsDBi | 47815 [O00264-1] 6345 |
TopDownProteomicsi | O00264-1 [O00264-1] |
2D gel databases
OGPi | O00264 |
PTM databases
iPTMneti | O00264 |
PhosphoSitePlusi | O00264 |
SwissPalmi | O00264 |
Expressioni
Tissue specificityi
Widely expressed, with highest expression in liver and kidney. Expressed by endometrial glands and stroma (at protein level) (PubMed:23793472).1 Publication
Gene expression databases
Bgeei | ENSG00000101856, Expressed in metanephros and 248 other tissues |
ExpressionAtlasi | O00264, baseline and differential |
Genevisiblei | O00264, HS |
Organism-specific databases
HPAi | ENSG00000101856, Tissue enhanced (liver) |
Interactioni
Subunit structurei
Homodimer. Forms stable homodimer through hydrophobic heme-heme stacking interactions (PubMed:26988023, PubMed:28396637).
Interacts with FECH; the interaction results in decreased FECH activity (PubMed:27599036).
Interacts with EGFR, CYP1A1 and CYP3A4; the interactions require PGRMC1 homodimerization (PubMed:28396637).
1 Publication3 PublicationsBinary interactionsi
Hide detailsO00264
GO - Molecular functioni
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 116068, 173 interactors |
CORUMi | O00264 |
IntActi | O00264, 93 interactors |
MINTi | O00264 |
STRINGi | 9606.ENSP00000217971 |
Miscellaneous databases
RNActi | O00264, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | O00264 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 72 – 171 | Cytochrome b5 heme-bindingAdd BLAST | 100 |
Domaini
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 107 and 131.By similarity
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1110, Eukaryota |
GeneTreei | ENSGT00940000160619 |
HOGENOMi | CLU_042860_5_0_1 |
InParanoidi | O00264 |
OMAi | MYANFAG |
PhylomeDBi | O00264 |
TreeFami | TF314562 |
Family and domain databases
Gene3Di | 3.10.120.10, 1 hit |
InterProi | View protein in InterPro IPR001199, Cyt_B5-like_heme/steroid-bd IPR036400, Cyt_B5-like_heme/steroid_sf |
Pfami | View protein in Pfam PF00173, Cyt-b5, 1 hit |
SMARTi | View protein in SMART SM01117, Cyt-b5, 1 hit |
SUPFAMi | SSF55856, SSF55856, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: O00264-1) [UniParc]FASTAAdd to basket
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
MAAEDVVATG ADPSDLESGG LLHEIFTSPL NLLLLGLCIF LLYKIVRGDQ
60 70 80 90 100
PAASGDSDDD EPPPLPRLKR RDFTPAELRR FDGVQDPRIL MAINGKVFDV
110 120 130 140 150
TKGRKFYGPE GPYGVFAGRD ASRGLATFCL DKEALKDEYD DLSDLTAAQQ
160 170 180 190
ETLSDWESQF TFKYHHVGKL LKEGEEPTVY SDEEEPKDES ARKND
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054710 | 110 – 162 | EGPYG…SQFTF → V in isoform 2. 1 PublicationAdd BLAST | 53 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y12711 mRNA Translation: CAA73248.1 AK293618 mRNA Translation: BAH11549.1 AC004835 Genomic DNA No translation available. CH471161 Genomic DNA Translation: EAW89881.1 BC034238 mRNA Translation: AAH34238.1 AJ249131 Genomic DNA Translation: CAB65109.1 |
CCDSi | CCDS14576.1 [O00264-1] CCDS65313.1 [O00264-2] |
RefSeqi | NP_001269550.1, NM_001282621.1 [O00264-2] NP_006658.1, NM_006667.4 [O00264-1] |
Genome annotation databases
Ensembli | ENST00000217971; ENSP00000217971; ENSG00000101856 [O00264-1] ENST00000535419; ENSP00000442821; ENSG00000101856 [O00264-2] |
GeneIDi | 10857 |
KEGGi | hsa:10857 |
UCSCi | uc011mts.4, human [O00264-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y12711 mRNA Translation: CAA73248.1 AK293618 mRNA Translation: BAH11549.1 AC004835 Genomic DNA No translation available. CH471161 Genomic DNA Translation: EAW89881.1 BC034238 mRNA Translation: AAH34238.1 AJ249131 Genomic DNA Translation: CAB65109.1 |
CCDSi | CCDS14576.1 [O00264-1] CCDS65313.1 [O00264-2] |
RefSeqi | NP_001269550.1, NM_001282621.1 [O00264-2] NP_006658.1, NM_006667.4 [O00264-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4X8Y | X-ray | 1.95 | A/B | 72-195 | [»] | |
SMRi | O00264 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 116068, 173 interactors |
CORUMi | O00264 |
IntActi | O00264, 93 interactors |
MINTi | O00264 |
STRINGi | 9606.ENSP00000217971 |
Chemistry databases
ChEMBLi | CHEMBL4105706 |
DrugBanki | DB00514, Dextromethorphan DB00540, Nortriptyline DB01104, Sertraline |
PTM databases
iPTMneti | O00264 |
PhosphoSitePlusi | O00264 |
SwissPalmi | O00264 |
Genetic variation databases
BioMutai | PGRMC1 |
2D gel databases
OGPi | O00264 |
Proteomic databases
EPDi | O00264 |
jPOSTi | O00264 |
MassIVEi | O00264 |
PaxDbi | O00264 |
PeptideAtlasi | O00264 |
PRIDEi | O00264 |
ProteomicsDBi | 47815 [O00264-1] 6345 |
TopDownProteomicsi | O00264-1 [O00264-1] |
Protocols and materials databases
Antibodypediai | 497, 205 antibodies |
DNASUi | 10857 |
Genome annotation databases
Ensembli | ENST00000217971; ENSP00000217971; ENSG00000101856 [O00264-1] ENST00000535419; ENSP00000442821; ENSG00000101856 [O00264-2] |
GeneIDi | 10857 |
KEGGi | hsa:10857 |
UCSCi | uc011mts.4, human [O00264-1] |
Organism-specific databases
CTDi | 10857 |
DisGeNETi | 10857 |
GeneCardsi | PGRMC1 |
HGNCi | HGNC:16090, PGRMC1 |
HPAi | ENSG00000101856, Tissue enhanced (liver) |
MIMi | 300435, gene |
neXtProti | NX_O00264 |
OpenTargetsi | ENSG00000101856 |
Orphaneti | 619, NON RARE IN EUROPE: Primary ovarian failure |
PharmGKBi | PA33248 |
VEuPathDBi | HostDB:ENSG00000101856.9 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1110, Eukaryota |
GeneTreei | ENSGT00940000160619 |
HOGENOMi | CLU_042860_5_0_1 |
InParanoidi | O00264 |
OMAi | MYANFAG |
PhylomeDBi | O00264 |
TreeFami | TF314562 |
Enzyme and pathway databases
PathwayCommonsi | O00264 |
Reactomei | R-HSA-6798695, Neutrophil degranulation |
Miscellaneous databases
BioGRID-ORCSi | 10857, 12 hits in 625 CRISPR screens |
ChiTaRSi | PGRMC1, human |
GeneWikii | PGRMC1 |
GenomeRNAii | 10857 |
Pharosi | O00264, Tbio |
PROi | PR:O00264 |
RNActi | O00264, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000101856, Expressed in metanephros and 248 other tissues |
ExpressionAtlasi | O00264, baseline and differential |
Genevisiblei | O00264, HS |
Family and domain databases
Gene3Di | 3.10.120.10, 1 hit |
InterProi | View protein in InterPro IPR001199, Cyt_B5-like_heme/steroid-bd IPR036400, Cyt_B5-like_heme/steroid_sf |
Pfami | View protein in Pfam PF00173, Cyt-b5, 1 hit |
SMARTi | View protein in SMART SM01117, Cyt-b5, 1 hit |
SUPFAMi | SSF55856, SSF55856, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PGRC1_HUMAN | |
Accessioni | O00264Primary (citable) accession number: O00264 Secondary accession number(s): B7Z1L3, Q9UGJ9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | January 23, 2007 | |
Last modified: | April 7, 2021 | |
This is version 192 of the entry and version 3 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - 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