EMP2_MOUSE
ID EMP2_MOUSE Reviewed; 172 AA.
AC O88662;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Epithelial membrane protein 2;
DE Short=EMP-2;
DE AltName: Full=Protein XMP;
GN Name=Emp2; Synonyms=Xmp;
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 [MRNA].
RX PubMed=9615230; DOI=10.1006/geno.1998.5238;
RA Ben-Porath I., Kozak C.A., Benvenisty N.;
RT "Chromosomal mapping of Tmp (Emp1), Xmp (Emp2), and Ymp (Emp3), genes
RT encoding membrane proteins related to Pmp22.";
RL Genomics 49:443-447(1998).
RN [2]
RP FUNCTION, INTERACTION WITH ITGB1, AND SUBCELLULAR LOCATION.
RX PubMed=12189152; DOI=10.1074/jbc.m206868200;
RA Wadehra M., Iyer R., Goodglick L., Braun J.;
RT "The tetraspan protein epithelial membrane protein-2 interacts with beta1
RT integrins and regulates adhesion.";
RL J. Biol. Chem. 277:41094-41100(2002).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12763482; DOI=10.1016/s1521-6616(03)00048-2;
RA Wadehra M., Su H., Gordon L.K., Goodglick L., Braun J.;
RT "The tetraspan protein EMP2 increases surface expression of class I major
RT histocompatibility complex proteins and susceptibility to CTL-mediated cell
RT death.";
RL Clin. Immunol. 107:129-136(2003).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=12710941; DOI=10.1016/s0014-4800(03)00009-1;
RA Wadehra M., Sulur G.G., Braun J., Gordon L.K., Goodglick L.;
RT "Epithelial membrane protein-2 is expressed in discrete anatomical regions
RT of the eye.";
RL Exp. Mol. Pathol. 74:106-112(2003).
RN [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14978215; DOI=10.1091/mbc.e03-07-0488;
RA Wadehra M., Goodglick L., Braun J.;
RT "The tetraspan protein EMP2 modulates the surface expression of caveolins
RT and glycosylphosphatidyl inositol-linked proteins.";
RL Mol. Biol. Cell 15:2073-2083(2004).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16216233; DOI=10.1016/j.ydbio.2005.09.003;
RA Wadehra M., Forbes A., Pushkarna N., Goodglick L., Gordon L.K.,
RA Williams C.J., Braun J.;
RT "Epithelial membrane protein-2 regulates surface expression of alphavbeta3
RT integrin in the endometrium.";
RL Dev. Biol. 287:336-345(2005).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16487956; DOI=10.1016/j.ydbio.2006.01.015;
RA Wadehra M., Dayal M., Mainigi M., Ord T., Iyer R., Braun J., Williams C.J.;
RT "Knockdown of the tetraspan protein epithelial membrane protein-2 inhibits
RT implantation in the mouse.";
RL Dev. Biol. 292:430-441(2006).
RN [8]
RP FUNCTION.
RX PubMed=17609206; DOI=10.1074/jbc.m702117200;
RA Forbes A., Wadehra M., Mareninov S., Morales S., Shimazaki K., Gordon L.K.,
RA Braun J.;
RT "The tetraspan protein EMP2 regulates expression of caveolin-1.";
RL J. Biol. Chem. 282:26542-26551(2007).
RN [9]
RP SUBCELLULAR LOCATION, AND INDUCTION BY ESTRADIOL AND PROGESTERONE.
RX PubMed=18400107; DOI=10.1186/1477-7827-6-15;
RA Wadehra M., Mainigi M., Morales S.A., Rao R.G., Gordon L.K., Williams C.J.,
RA Braun J.;
RT "Steroid hormone regulation of EMP2 expression and localization in the
RT endometrium.";
RL Reprod. Biol. Endocrinol. 6:15-15(2008).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=28295343; DOI=10.1002/path.4893;
RA Williams C.J., Chu A., Jefferson W.N., Casero D., Sudhakar D., Khurana N.,
RA Hogue C.P., Aryasomayajula C., Patel P., Sullivan P., Padilla-Banks E.,
RA Mohandessi S., Janzen C., Wadehra M.;
RT "Epithelial membrane protein 2 (EMP2) deficiency alters placental
RT angiogenesis, mimicking features of human placental insufficiency.";
RL J. Pathol. 242:246-259(2017).
RN [11]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=30773261; DOI=10.1016/j.bbrc.2019.02.048;
RA Liu Y., Dakou E., Meng Y., Leyns L.;
RT "Loss of Emp2 compromises cardiogenic differentiation in mouse embryonic
RT stem cells.";
RL Biochem. Biophys. Res. Commun. 511:173-178(2019).
RN [12]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=31550239; DOI=10.1172/jci127144;
RA Lin W.C., Gowdy K.M., Madenspacher J.H., Zemans R.L., Yamamoto K.,
RA Lyons-Cohen M., Nakano H., Janardhan K., Williams C.J., Cook D.N.,
RA Mizgerd J.P., Fessler M.B.;
RT "Epithelial membrane protein 2 governs transepithelial migration of
RT neutrophils into the airspace.";
RL J. Clin. Invest. 130:157-170(2020).
CC -!- FUNCTION: Functions as a key regulator of cell membrane composition by
CC regulating protein surface expression. Also, plays a role in regulation
CC of processes including cell migration, cell proliferation, cell
CC contraction and cell adhesion. Regulates transepithelial migration of
CC neutrophils into the alveolar lumen, potentially via mediation of cell
CC surface expression of adhesion markers and lipid raft formation
CC (PubMed:31550239). Negatively regulates caveolae formation by reducing
CC CAV1 expression and CAV1 amount by increasing lysosomal degradation
CC (PubMed:17609206, PubMed:14978215). Facilitates surface trafficking and
CC the formation of lipid rafts bearing GPI-anchor proteins
CC (PubMed:14978215). Regulates surface expression of MHC1 and ICAM1
CC proteins increasing susceptibility to T-cell mediated cytotoxicity
CC (PubMed:12763482). Regulates the plasma membrane expression of the
CC integrin heterodimers ITGA6-ITGB1, ITGA5-ITGB3 and ITGA5-ITGB1
CC resulting in modulation of cell-matrix adhesion (PubMed:12189152). Also
CC regulates many processes through PTK2. Regulates blood vessel
CC endothelial cell migration and angiogenesis by regulating VEGF protein
CC expression through PTK2 activation (By similarity). Regulates cell
CC migration and cell contraction through PTK2 and SRC activation (By
CC similarity). Regulates focal adhesion density, F-actin conformation and
CC cell adhesion capacity through interaction with PTK2 (By similarity).
CC Positively regulates cell proliferation (By similarity). Plays a role
CC during cell death and cell blebbing (By similarity). Promotes
CC angiogenesis and vasculogenesis through induction of VEGFA via a HIF1A-
CC dependent pathway (By similarity). Also plays a role in embryo
CC implantation by regulating surface trafficking of integrin heterodimer
CC ITGA5-ITGB3 (PubMed:16487956, PubMed:16216233). Plays a role in
CC placental angiogenesis and uterine natural killer cell regulation at
CC the maternal-fetal placental interface, however not required in the
CC maternal tissues for a viable pregnancy (PubMed:28295343). Involved in
CC the early stages of embryogenic development and cardiogenesis,
CC potentially via regulation of epithelial-mesenchymal transition timing
CC (PubMed:30773261). May play a role in glomerular filtration (By
CC similarity). {ECO:0000250|UniProtKB:F1QIK8,
CC ECO:0000250|UniProtKB:P54851, ECO:0000269|PubMed:12189152,
CC ECO:0000269|PubMed:12763482, ECO:0000269|PubMed:14978215,
CC ECO:0000269|PubMed:16216233, ECO:0000269|PubMed:16487956,
CC ECO:0000269|PubMed:17609206, ECO:0000269|PubMed:28295343,
CC ECO:0000269|PubMed:30773261, ECO:0000269|PubMed:31550239}.
CC -!- SUBUNIT: Interacts with PTK2; regulates PTK2 activation and
CC localization (By similarity). Interacts with ITGB3; regulates the
CC levels of the heterodimer ITGA5-ITGB3 integrin surface expression (By
CC similarity). Interacts with P2RX7 (via C-terminus) (By similarity).
CC Interacts with ITGB1; the interaction may be direct or indirect and
CC ITGB1 has a heterodimer form (PubMed:12189152).
CC {ECO:0000250|UniProtKB:P54851, ECO:0000269|PubMed:12189152}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:12189152, ECO:0000269|PubMed:14978215,
CC ECO:0000269|PubMed:16487956, ECO:0000305}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:12189152}. Apical cell
CC membrane {ECO:0000269|PubMed:16216233, ECO:0000269|PubMed:18400107}.
CC Membrane raft {ECO:0000269|PubMed:12763482,
CC ECO:0000269|PubMed:14978215}. Cytoplasm {ECO:0000269|PubMed:16216233,
CC ECO:0000269|PubMed:18400107, ECO:0000269|PubMed:28295343}. Nucleus
CC {ECO:0000250|UniProtKB:Q66HH2}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:28295343}. Note=Localizes in cytoplasm, foot
CC processes and cell bodies of podocytes and nucleus of endothelial cells
CC of kidney (By similarity). Localizes to the apical cell surface in the
CC luminal epithelium and glandular epithelium (PubMed:16487956).
CC Colocalized with ITGB1 and GPI-anchor proteins on plasma membrane
CC (PubMed:12189152) (PubMed:14978215). {ECO:0000250|UniProtKB:Q66HH2,
CC ECO:0000269|PubMed:12189152, ECO:0000269|PubMed:14978215,
CC ECO:0000269|PubMed:16487956}.
CC -!- TISSUE SPECIFICITY: Expressed in alveolar epithelial type 1, alveolar
CC epithelial type 2 and airway epithelial cells (at protein level)
CC (PubMed:31550239). Expressed in both the endometrial epithelial and
CC stromal cells during the embryo implantation period (PubMed:16487956).
CC Expressed in the corneal epithelium, the sclera, the nerve fiber layer
CC of the inner retina and retinal ganglion cell layer, the nonpigmented
CC epithelium of the ciliary body and the optic nerve (PubMed:12710941).
CC {ECO:0000269|PubMed:12710941, ECO:0000269|PubMed:16487956,
CC ECO:0000269|PubMed:31550239}.
CC -!- DEVELOPMENTAL STAGE: Expressed from day 3 of gastrulation, expression
CC peaks on day 6 before decreasing on days 8 and 10 (PubMed:30773261).
CC Expressed throughout gestation in the embryo proper, trophoblastic
CC stems cells in the ectoplacental cone and decidual cells
CC (PubMed:28295343). Expressed in trophoblast giant cells and maternal
CC decidua in the placenta and in the endometrium at 9.5 dpc
CC (PubMed:28295343). Expressed in the developing heart, head and otic
CC vesicle at 9.5 dpc (PubMed:30773261). Abundantly expressed in giant
CC cells and weakly expressed in labyrinthine trophoblasts and
CC spongiotrophoblasts in the junctional zone, also expressed within the
CC cytoplasm and perinuclear region of pre-glycogen cells at 12 dpc
CC (PubMed:28295343). Expression in all trophoblast populations reduces as
CC placentas near term (PubMed:28295343). {ECO:0000269|PubMed:28295343,
CC ECO:0000269|PubMed:30773261}.
CC -!- INDUCTION: Induced by progesterone; initially expressed in the uterus
CC luminal epithelium spreading to the glandular epithelium 48 hours after
CC treatment, increases expression at the plasma membrane
CC (PubMed:18400107). Induced by estradiol in the cytoplasm of endometrial
CC tissue; expression is induced 48 hours after initiation of estradiol
CC treatment (PubMed:18400107). {ECO:0000269|PubMed:18400107}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice show a longer time to achieve
CC pregnancy and a reduced litter size as a result of viable knockout
CC embryos (PubMed:28295343). Increase in fibrin deposition throughout the
CC decidua basalis and junctional zones in placentas (PubMed:28295343).
CC Reduced placental vasculogenesis at 9.5dpc and altered vascular
CC organization is evident at 12.5 dpc (PubMed:28295343). Increased
CC collagen deposition in placentas including around the placental
CC labyrinth at 16.5 dpc (PubMed:28295343). Increase in Hif1a expression
CC in placental decidual leukocytes at 9.5 and 12.5 dpc, expression
CC returns to normal by 16.5 dpc (PubMed:28295343). Increase in uterine
CC natural killer cells in the placental decidua basalis throughout
CC gestation (PubMed:28295343). Reduced influx of neutrophils to the
CC airspace after intrapulmonary inoculation with the chemokine Cxcl1 and
CC an increase in interstitial neutrophils in lipopolysaccharide
CC challenged lungs (PubMed:31550239). Increased survival during
CC K.pneumoniae lung infection, as a result of attenuated injury to the
CC alveolocapillary barrier and decreased systemic inflammation
CC (PubMed:31550239). Significant decrease in bacterial burden in the
CC lungs, bloodstream, and spleen 48 hours following K.pneumoniae
CC suggesting enhanced pathogen clearance in the lungs and reduced
CC extrapulmonary dissemination (PubMed:31550239). Increase in surface
CC Cd47 and decrease in surface Icam1 and Itgb3 on alveolar epithelial
CC type 1 cells accompanied by a reduction in the number of lipid rafts
CC (PubMed:31550239). Increase in Cav1 and Cav2 expression in lung tissues
CC (PubMed:31550239). {ECO:0000269|PubMed:28295343,
CC ECO:0000269|PubMed:31550239}.
CC -!- SIMILARITY: Belongs to the PMP-22/EMP/MP20 family. {ECO:0000305}.
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DR EMBL; AF083876; AAC33108.1; -; mRNA.
DR CCDS; CCDS37250.1; -.
DR RefSeq; NP_031955.2; NM_007929.2.
DR AlphaFoldDB; O88662; -.
DR SMR; O88662; -.
DR STRING; 10090.ENSMUSP00000077466; -.
DR GlyGen; O88662; 2 sites.
DR PhosphoSitePlus; O88662; -.
DR PaxDb; O88662; -.
DR PRIDE; O88662; -.
DR ProteomicsDB; 275749; -.
DR Antibodypedia; 11432; 131 antibodies from 23 providers.
DR DNASU; 13731; -.
DR Ensembl; ENSMUST00000078357; ENSMUSP00000077466; ENSMUSG00000022505.
DR GeneID; 13731; -.
DR KEGG; mmu:13731; -.
DR UCSC; uc007ydj.1; mouse.
DR CTD; 2013; -.
DR MGI; MGI:1098726; Emp2.
DR VEuPathDB; HostDB:ENSMUSG00000022505; -.
DR eggNOG; ENOG502RYYE; Eukaryota.
DR GeneTree; ENSGT00950000182696; -.
DR HOGENOM; CLU_138632_0_0_1; -.
DR InParanoid; O88662; -.
DR OMA; ADIWRVC; -.
DR OrthoDB; 1345659at2759; -.
DR PhylomeDB; O88662; -.
DR TreeFam; TF330414; -.
DR BioGRID-ORCS; 13731; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Emp2; mouse.
DR PRO; PR:O88662; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; O88662; protein.
DR Bgee; ENSMUSG00000022505; Expressed in right lung lobe and 254 other tissues.
DR ExpressionAtlas; O88662; baseline and differential.
DR Genevisible; O88662; MM.
DR GO; GO:0045177; C:apical part of cell; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005178; F:integrin binding; IPI:UniProtKB.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0007015; P:actin filament organization; ISS:UniProtKB.
DR GO; GO:0070252; P:actin-mediated cell contraction; ISS:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0032060; P:bleb assembly; ISS:UniProtKB.
DR GO; GO:0043534; P:blood vessel endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0008219; P:cell death; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0007160; P:cell-matrix adhesion; ISS:UniProtKB.
DR GO; GO:0045022; P:early endosome to late endosome transport; IDA:UniProtKB.
DR GO; GO:0007566; P:embryo implantation; IMP:UniProtKB.
DR GO; GO:0060136; P:embryonic process involved in female pregnancy; IMP:UniProtKB.
DR GO; GO:0060914; P:heart formation; IMP:UniProtKB.
DR GO; GO:0001765; P:membrane raft assembly; IDA:UniProtKB.
DR GO; GO:0001787; P:natural killer cell proliferation; IMP:UniProtKB.
DR GO; GO:1990266; P:neutrophil migration; IMP:UniProtKB.
DR GO; GO:0044854; P:plasma membrane raft assembly; IMP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0062043; P:positive regulation of cardiac epithelial to mesenchymal transition; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISO:MGI.
DR GO; GO:2001046; P:positive regulation of integrin-mediated signaling pathway; IMP:MGI.
DR GO; GO:0034394; P:protein localization to cell surface; IMP:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; IDA:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; IDA:UniProtKB.
DR GO; GO:0010594; P:regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0003093; P:regulation of glomerular filtration; ISS:UniProtKB.
DR GO; GO:0043549; P:regulation of kinase activity; ISS:UniProtKB.
DR GO; GO:2001212; P:regulation of vasculogenesis; ISS:UniProtKB.
DR GO; GO:0001913; P:T cell mediated cytotoxicity; IDA:UniProtKB.
DR InterPro; IPR003933; EMP-2.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR InterPro; IPR004032; PMP22_EMP_MP20.
DR PANTHER; PTHR10671:SF32; PTHR10671:SF32; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01453; EPMEMFAMILY.
DR PRINTS; PR01455; EPMEMPROT2.
DR PROSITE; PS01221; PMP22_1; 1.
DR PROSITE; PS01222; PMP22_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Glycoprotein; Golgi apparatus; Membrane; Nucleus;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..172
FT /note="Epithelial membrane protein 2"
FT /id="PRO_0000164659"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 47
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 172 AA; 19747 MW; 6110C073BC75FB6D CRC64;
MLVILAFIIV FHIVSTALLF ISTIDNAWWV GDSFSADLWR VCTNSTNCTE INELTGPEAF
EGYSVMQAVQ ATMILSTILS CISFLIFLLQ LFRLKQGERF VLTSIIQLMS CLCVMIGASI
YTDRRQDLHQ QNRKLYYLLQ EGSYGYSFIL AWVAFAFTFI SGLMYMILRK RK
