PGRC2_MOUSE
ID PGRC2_MOUSE Reviewed; 217 AA.
AC Q80UU9;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Membrane-associated progesterone receptor component 2 {ECO:0000305};
GN Name=Pgrmc2 {ECO:0000312|MGI:MGI:1918054};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-217.
RC STRAIN=129; TISSUE=Mammary tumor;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-202, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-205, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-205, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-205, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=28005395; DOI=10.1210/en.2016-1701;
RA Clark N.C., Pru C.A., Yee S.P., Lydon J.P., Peluso J.J., Pru J.K.;
RT "Conditional Ablation of Progesterone Receptor Membrane Component 2 Causes
RT Female Premature Reproductive Senescence.";
RL Endocrinology 158:640-651(2017).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP PGRMC1.
RX PubMed=31748741; DOI=10.1038/s41586-019-1774-2;
RA Galmozzi A., Kok B.P., Kim A.S., Montenegro-Burke J.R., Lee J.Y.,
RA Spreafico R., Mosure S., Albert V., Cintron-Colon R., Godio C., Webb W.R.,
RA Conti B., Solt L.A., Kojetin D., Parker C.G., Peluso J.J., Pru J.K.,
RA Siuzdak G., Cravatt B.F., Saez E.;
RT "PGRMC2 is an intracellular haem chaperone critical for adipocyte
RT function.";
RL Nature 576:138-142(2019).
CC -!- FUNCTION: Required for the maintenance of uterine histoarchitecture and
CC normal female reproductive lifespan (PubMed:28005395). May serve as a
CC universal non-classical progesterone receptor in the uterus (Probable).
CC Intracellular heme chaperone required for delivery of labile, or
CC signaling heme, to the nucleus. Plays a role in adipocyte function and
CC systemic glucose homeostasis. In brown fat, which has a high demand for
CC heme, delivery of labile heme in the nucleus regulates the activity of
CC heme-responsive transcriptional repressors such as NR1D1 and BACH1
CC (PubMed:31748741). {ECO:0000269|PubMed:28005395,
CC ECO:0000269|PubMed:31748741, ECO:0000305|PubMed:28005395}.
CC -!- SUBUNIT: Interacts with PGRMC1 (PubMed:31748741). Interacts with AAAS
CC (By similarity). {ECO:0000250|UniProtKB:O15173,
CC ECO:0000269|PubMed:31748741}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Nucleus envelope {ECO:0000250|UniProtKB:O15173}.
CC Endoplasmic reticulum {ECO:0000250|UniProtKB:O15173}.
CC -!- TISSUE SPECIFICITY: Expressed in brown adipose tissue, white adipose
CC tissue, liver, heart, skeletal muscle, brain and adrenal gland.
CC {ECO:0000269|PubMed:31748741}.
CC -!- DOMAIN: The cytochrome b5 heme-binding domain lacks the conserved iron-
CC binding His residues at positions 131 and 155. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Adipose tissue-specific knockout mice adapted to
CC 30 degrees Celsius show no difference in body weight or white adipose
CC tissue (WAT) mass but have reduced brown adipose tissue (BAT) weight
CC relative to their wild-type littermates. BAT loses its distinctive
CC reddish color. In contrast to wild-type mice, which activate
CC thermogenesis and preserve body temperature when exposed to cold (4
CC degrees Celsius), mutants rapidly become hypothermic and die if not
CC rescued. They have a total heme content reduced of about 60%. Mutants
CC housed at room temperature and fed a high-fat diet (HFD) show no
CC differences in body weight or composition, except for decreased BAT
CC mass. However, they have higher fasting glycaemia and decreased glucose
CC tolerance and insulin sensitivity. They also exhibit hyperlipidaemia
CC and exacerbated liver steatosis with about 70% more triglycerides
CC (PubMed:31748741). Conditional knockout from female reproductive
CC tissues results in postimplantation embryonic death leading to
CC subfertility, with female mice producing 47% fewer pups/litter than
CC wild-types. They undergo premature reproductive senescence by parities
CC 2 to 5, producing 37.8% fewer litters overall during the trial compared
CC with wild-types (PubMed:28005395). Double conditional knockout for
CC PGRMC1 and PGRMC2 from female reproductive tissues results in
CC postimplantation embryonic death leading to subfertility, with female
CC mice producing fewer pups/litter than wild-types. They undergo
CC premature reproductive senescence, producing fewer litters overall
CC during the trial compared with wild-types (PubMed:28005395).
CC {ECO:0000269|PubMed:28005395, ECO:0000269|PubMed:31748741}.
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:O15173}.
CC -!- SIMILARITY: Belongs to the cytochrome b5 family. MAPR subfamily.
CC {ECO:0000305}.
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DR EMBL; AC100511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044759; AAH44759.1; -; mRNA.
DR CCDS; CCDS50899.1; -.
DR RefSeq; NP_081834.1; NM_027558.1.
DR AlphaFoldDB; Q80UU9; -.
DR SMR; Q80UU9; -.
DR BioGRID; 214264; 7.
DR IntAct; Q80UU9; 6.
DR MINT; Q80UU9; -.
DR STRING; 10090.ENSMUSP00000056643; -.
DR iPTMnet; Q80UU9; -.
DR PhosphoSitePlus; Q80UU9; -.
DR SwissPalm; Q80UU9; -.
DR EPD; Q80UU9; -.
DR jPOST; Q80UU9; -.
DR MaxQB; Q80UU9; -.
DR PaxDb; Q80UU9; -.
DR PeptideAtlas; Q80UU9; -.
DR PRIDE; Q80UU9; -.
DR ProteomicsDB; 289480; -.
DR Antibodypedia; 27009; 277 antibodies from 32 providers.
DR Ensembl; ENSMUST00000058578; ENSMUSP00000056643; ENSMUSG00000049940.
DR GeneID; 70804; -.
DR KEGG; mmu:70804; -.
DR UCSC; uc008pce.2; mouse.
DR CTD; 10424; -.
DR MGI; MGI:1918054; Pgrmc2.
DR VEuPathDB; HostDB:ENSMUSG00000049940; -.
DR eggNOG; KOG1110; Eukaryota.
DR GeneTree; ENSGT00940000159744; -.
DR HOGENOM; CLU_042860_1_0_1; -.
DR InParanoid; Q80UU9; -.
DR OMA; MAVNMKI; -.
DR OrthoDB; 1331617at2759; -.
DR PhylomeDB; Q80UU9; -.
DR TreeFam; TF314562; -.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013405; RHOD GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR BioGRID-ORCS; 70804; 5 hits in 73 CRISPR screens.
DR ChiTaRS; Pgrmc2; mouse.
DR PRO; PR:Q80UU9; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q80UU9; protein.
DR Bgee; ENSMUSG00000049940; Expressed in otic placode and 261 other tissues.
DR Genevisible; Q80UU9; MM.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0015232; F:heme transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW.
DR GO; GO:0060612; P:adipose tissue development; ISS:UniProtKB.
DR GO; GO:0015886; P:heme transport; IDA:UniProtKB.
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 Endoplasmic reticulum; Lipid-binding; Membrane; Nucleus; Phosphoprotein;
KW Receptor; Reference proteome; Steroid-binding; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..217
FT /note="Membrane-associated progesterone receptor component
FT 2"
FT /id="PRO_0000121744"
FT TRANSMEM 40..62
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 96..195
FT /note="Cytochrome b5 heme-binding"
FT REGION 196..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 84
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15173"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15173"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 204
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O15173"
FT MOD_RES 205
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18630941,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
SQ SEQUENCE 217 AA; 23334 MW; 0291B0EFE8AD3403 CRC64;
MAAGDGDVKL STLGSGGESG GDGSPGGAGA TAARSSWVAA LLATGGEMLL NVALVALVLL
GAYRLWVRWG RRGLCSGPGA GEESPAATLP RMKKRDFSLE QLRQYDGART PRILLAVNGK
VFDVTKGSKF YGPAGPYGIF AGRDASRGLA TFCLDKDALR DEYDDLSDLN AVQMESVREW
EMQFKEKYDY VGRLLKPGEE PSEYTDEEDT KDHSKQD
