PGRC1_RAT
ID PGRC1_RAT Reviewed; 195 AA.
AC P70580; O70606; Q549C4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Membrane-associated progesterone receptor component 1;
DE Short=mPR {ECO:0000250|UniProtKB:O00264};
DE AltName: Full=25-DX {ECO:0000303|Ref.5};
DE AltName: Full=Acidic 25 kDa protein {ECO:0000303|Ref.5};
DE AltName: Full=Ventral midline antigen {ECO:0000303|PubMed:10656251};
DE Short=VEMA {ECO:0000303|PubMed:10656251};
GN Name=Pgrmc1 {ECO:0000312|RGD:70890}; Synonyms=25dx, Lewi, Pgrmc;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=9006096; DOI=10.1093/carcin/17.12.2609;
RA Selmin O., Lucier G.W., Clark G.C., Tritscher A.M., Vanden Heuvel J.P.,
RA Gastel J.A., Walker N.J., Sutter T.R., Bell D.A.;
RT "Isolation and characterization of a novel gene induced by 2,3,7,8-
RT tetrachlorodibenzo-p-dioxin in rat liver.";
RL Carcinogenesis 17:2609-2615(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344; TISSUE=Liver;
RA Noelte I., Sohn K., Wegehingl S., Wieland F.;
RT "Rat homologue to a putative progesterone binding protein: molecular
RT characterization and localization.";
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RX PubMed=10656251; DOI=10.1006/mcne.1999.0794;
RA Runko E., Wideman C., Kaprielian Z.;
RT "Cloning and expression of VEMA: a novel ventral midline antigen in the rat
RT CNS.";
RL Mol. Cell. Neurosci. 14:428-443(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 PROTEIN SEQUENCE OF 2-15.
RC STRAIN=Wistar; TISSUE=Liver;
RA Hubbard M.J., McHugh N.J.;
RT "Acidic 25-kDa protein in rat liver microsomes.";
RL Submitted (JUL-1999) to UniProtKB.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Component of a progesterone-binding protein complex. Binds
CC progesterone. Has many reported cellular functions (heme homeostasis,
CC interaction with CYPs). Required for the maintenance of uterine
CC histoarchitecture and normal female reproductive lifespan.
CC Intracellular heme chaperone. Regulates heme synthesis via interactions
CC with FECH and acts as a heme donor for at least some hemoproteins (By
CC similarity). May be implicated in 2,3,7,8-tetrachlorodibenzo-p-dioxin
CC (TCDD) immunotoxicity (PubMed:9006096). {ECO:0000250|UniProtKB:O00264,
CC ECO:0000269|PubMed:9006096}.
CC -!- SUBUNIT: Homodimer. Forms stable homodimer through hydrophobic heme-
CC heme stacking interactions. Interacts with FECH; the interaction
CC results in decreased FECH activity (By similarity). Interacts with
CC EGFR, CYP1A1 and CYP3A4; the interactions require PGRMC1
CC homodimerization (By similarity). {ECO:0000250|UniProtKB:O00264}.
CC -!- SUBCELLULAR LOCATION: Microsome membrane
CC {ECO:0000250|UniProtKB:Q95250}; Single-pass membrane protein
CC {ECO:0000255}. Smooth endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O00264}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:O55022}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:O00264}; Extracellular side
CC {ECO:0000250|UniProtKB:O55022}.
CC -!- TISSUE SPECIFICITY: Expressed at high levels in lung, liver, kidney and
CC brain, low in testis and spleen. Not expressed in heart and skeletal
CC muscle.
CC -!- INDUCTION: By dioxin.
CC -!- DOMAIN: The cytochrome b5 heme-binding domain lacks the conserved iron-
CC binding His residues at positions 107 and 131. {ECO:0000250}.
CC -!- MISCELLANEOUS: Non-classical progesterone receptors involved in
CC extranuclear signaling are classified in 2 groups: the class II
CC progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5,
CC PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding
CC protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).
CC {ECO:0000250|UniProtKB:O00264}.
CC -!- SIMILARITY: Belongs to the cytochrome b5 family. MAPR subfamily.
CC {ECO:0000305}.
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DR EMBL; U63315; AAB07125.1; -; mRNA.
DR EMBL; AJ005837; CAA06732.1; -; mRNA.
DR EMBL; AF163321; AAF17359.1; -; mRNA.
DR EMBL; BC062073; AAH62073.1; -; mRNA.
DR RefSeq; NP_068534.1; NM_021766.1.
DR AlphaFoldDB; P70580; -.
DR SMR; P70580; -.
DR BioGRID; 253702; 1.
DR IntAct; P70580; 1.
DR STRING; 10116.ENSRNOP00000017101; -.
DR BindingDB; P70580; -.
DR DrugCentral; P70580; -.
DR iPTMnet; P70580; -.
DR PhosphoSitePlus; P70580; -.
DR jPOST; P70580; -.
DR PaxDb; P70580; -.
DR PRIDE; P70580; -.
DR Ensembl; ENSRNOT00000017101; ENSRNOP00000017101; ENSRNOG00000012786.
DR GeneID; 291948; -.
DR KEGG; rno:291948; -.
DR UCSC; RGD:70890; rat.
DR CTD; 10857; -.
DR RGD; 70890; Pgrmc1.
DR eggNOG; KOG1110; Eukaryota.
DR GeneTree; ENSGT00940000160619; -.
DR InParanoid; P70580; -.
DR OrthoDB; 1331617at2759; -.
DR PhylomeDB; P70580; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:P70580; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000012786; Expressed in liver and 18 other tissues.
DR ExpressionAtlas; P70580; baseline and differential.
DR Genevisible; P70580; RN.
DR GO; GO:0044297; C:cell body; IDA:ARUK-UCL.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR GO; GO:0014069; C:postsynaptic density; TAS:ARUK-UCL.
DR GO; GO:0030868; C:smooth endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IDA:ARUK-UCL.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0008306; P:associative learning; IGI:ARUK-UCL.
DR GO; GO:0007411; P:axon guidance; IEP:RGD.
DR GO; GO:0006783; P:heme biosynthetic process; ISS:UniProtKB.
DR GO; GO:0007613; P:memory; IGI:ARUK-UCL.
DR GO; GO:0099563; P:modification of synaptic structure; IGI:ARUK-UCL.
DR GO; GO:1905809; P:negative regulation of synapse organization; IGI:ARUK-UCL.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IMP:ARUK-UCL.
DR Gene3D; 3.10.120.10; -; 1.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR Pfam; PF00173; Cyt-b5; 1.
DR SMART; SM01117; Cyt-b5; 1.
DR SUPFAM; SSF55856; SSF55856; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Iron; Lipid-binding;
KW Membrane; Metal-binding; Microsome; Mitochondrion;
KW Mitochondrion outer membrane; Phosphoprotein; Receptor; Reference proteome;
KW Steroid-binding; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.5"
FT CHAIN 2..195
FT /note="Membrane-associated progesterone receptor component
FT 1"
FT /id="PRO_0000121742"
FT TOPO_DOM 2..24
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..195
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 72..171
FT /note="Cytochrome b5 heme-binding"
FT REGION 51..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 113
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:O00264"
FT MOD_RES 54
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O00264"
FT MOD_RES 74
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O00264"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100,
FT ECO:0007744|PubMed:22673903"
FT CONFLICT 161..167
FT /note="TFKYHHV -> SSPSSTITW (in Ref. 1; AAB07125)"
FT /evidence="ECO:0000305"
FT CONFLICT 172..174
FT /note="KEG -> EGA (in Ref. 1; AAB07125)"
FT /evidence="ECO:0000305"
FT CONFLICT 178
FT /note="T -> I (in Ref. 1; AAB07125)"
FT /evidence="ECO:0000305"
FT CONFLICT 186..195
FT /note="PKDEAARKSD -> QKMRLLGRVTEAVSGAYLFLYFAKSFVTFQSVFTTW
FT (in Ref. 1; AAB07125)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 195 AA; 21598 MW; 1E8F8605AA3098A2 CRC64;
MAAEDVVATG ADPSELEGGG LLQEIFTSPL NLLLLGLCIF LLYKIVRGDQ PGASGDNDDD
EPPPLPRLKP RDFTPAELRR YDGVQDPRIL MAINGKVFDV TKGRKFYGPE GPYGVFAGRD
ASRGLATFCL DKEALKDEYD DLSDLTPAQQ ETLNDWDSQF TFKYHHVGKL LKEGEEPTVY
SDDEEPKDEA ARKSD
