EMP2_RAT
ID EMP2_RAT Reviewed; 172 AA.
AC Q66HH2;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Epithelial membrane protein 2;
DE Short=EMP-2;
GN Name=Emp2;
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 {ECO:0000312|EMBL:AAH81865.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [4]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=24814193; DOI=10.1016/j.ajhg.2014.04.010;
RA Gee H.Y., Ashraf S., Wan X., Vega-Warner V., Esteve-Rudd J., Lovric S.,
RA Fang H., Hurd T.W., Sadowski C.E., Allen S.J., Otto E.A., Korkmaz E.,
RA Washburn J., Levy S., Williams D.S., Bakkaloglu S.A., Zolotnitskaya A.,
RA Ozaltin F., Zhou W., Hildebrandt F.;
RT "Mutations in EMP2 cause childhood-onset nephrotic syndrome.";
RL Am. J. Hum. Genet. 94:884-890(2014).
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 (By
CC similarity). Negatively regulates caveolae formation by reducing CAV1
CC expression and CAV1 amount by increasing lysosomal degradation (By
CC similarity). Facilitates surface trafficking and the formation of lipid
CC rafts bearing GPI-anchor proteins (By similarity). Regulates surface
CC expression of MHC1 and ICAM1 proteins increasing susceptibility to T-
CC cell mediated cytotoxicity (By similarity). Regulates the plasma
CC membrane expression of the integrin heterodimers ITGA6-ITGB1, ITGA5-
CC ITGB3 and ITGA5-ITGB1 resulting in modulation of cell-matrix adhesion
CC (By similarity). Also regulates many processes through PTK2 (By
CC similarity). Regulates blood vessel endothelial cell migration and
CC angiogenesis by regulating VEGF protein expression through PTK2
CC activation (By similarity). Regulates cell migration and cell
CC contraction through PTK2 and SRC activation (By similarity). Regulates
CC focal adhesion density, F-actin conformation and cell adhesion capacity
CC through interaction with PTK2 (By similarity). Positively regulates
CC cell proliferation (By similarity). Plays a role during cell death and
CC cell blebbing. Promotes angiogenesis and vasculogenesis through
CC induction of VEGFA via a HIF1A-dependent pathway (By similarity). Also
CC plays a role in embryo implantation by regulating surface trafficking
CC of integrin heterodimer ITGA5-ITGB3 (By similarity). 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 (By similarity). Involved in
CC the early stages of embryogenic development and cardiogenesis,
CC potentially via regulation of epithelial-mesenchymal transition timing
CC (By similarity). May play a role in glomerular filtration (By
CC similarity). {ECO:0000250|UniProtKB:F1QIK8,
CC ECO:0000250|UniProtKB:O88662, ECO:0000250|UniProtKB:P54851}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:O88662, ECO:0000250|UniProtKB:P54851}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:O88662}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:O88662,
CC ECO:0000250|UniProtKB:P54851}. Apical cell membrane
CC {ECO:0000250|UniProtKB:O88662}. Membrane raft
CC {ECO:0000250|UniProtKB:O88662, ECO:0000250|UniProtKB:P54851}. Cytoplasm
CC {ECO:0000250|UniProtKB:O88662, ECO:0000250|UniProtKB:P54851,
CC ECO:0000269|PubMed:24814193}. Nucleus {ECO:0000269|PubMed:24814193}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:O88662}.
CC Note=Localizes in cytoplasm, foot processes and cell bodies of
CC podocytes and nucleus of endothelial cells of kidney (PubMed:24814193).
CC Localizes to the apical cell surface in the luminal epithelium and
CC glandular epithelium. Colocalized with ITGB1 and GPI-anchor proteins on
CC plasma membrane (By similarity). {ECO:0000250|UniProtKB:O88662,
CC ECO:0000269|PubMed:24814193}.
CC -!- TISSUE SPECIFICITY: Expressed in glomeruli.
CC {ECO:0000269|PubMed:24814193}.
CC -!- SIMILARITY: Belongs to the PMP-22/EMP/MP20 family. {ECO:0000305}.
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DR EMBL; AABR06062648; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06062649; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06062650; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06062651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR06062652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474017; EDL96228.1; -; Genomic_DNA.
DR EMBL; BC081865; AAH81865.1; -; mRNA.
DR RefSeq; NP_001007722.1; NM_001007721.1.
DR AlphaFoldDB; Q66HH2; -.
DR SMR; Q66HH2; -.
DR STRING; 10116.ENSRNOP00000003615; -.
DR PaxDb; Q66HH2; -.
DR Ensembl; ENSRNOT00000003615; ENSRNOP00000003615; ENSRNOG00000002664.
DR GeneID; 360468; -.
DR KEGG; rno:360468; -.
DR UCSC; RGD:1359629; rat.
DR CTD; 2013; -.
DR RGD; 1359629; Emp2.
DR eggNOG; ENOG502RYYE; Eukaryota.
DR GeneTree; ENSGT00950000182696; -.
DR HOGENOM; CLU_138632_0_0_1; -.
DR InParanoid; Q66HH2; -.
DR OMA; ADIWRVC; -.
DR OrthoDB; 1345659at2759; -.
DR PhylomeDB; Q66HH2; -.
DR TreeFam; TF330414; -.
DR PRO; PR:Q66HH2; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Proteomes; UP000234681; Chromosome 10.
DR Bgee; ENSRNOG00000002664; Expressed in lung and 18 other tissues.
DR Genevisible; Q66HH2; RN.
DR GO; GO:0045177; C:apical part of cell; ISS:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005794; C:Golgi apparatus; ISS: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; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0019900; F:kinase binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0007566; P:embryo implantation; ISS:UniProtKB.
DR GO; GO:0060136; P:embryonic process involved in female pregnancy; ISS:UniProtKB.
DR GO; GO:0060914; P:heart formation; ISS:UniProtKB.
DR GO; GO:0001765; P:membrane raft assembly; ISS:UniProtKB.
DR GO; GO:0001787; P:natural killer cell proliferation; ISS:UniProtKB.
DR GO; GO:1990266; P:neutrophil migration; ISS:UniProtKB.
DR GO; GO:0044854; P:plasma membrane raft assembly; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0062043; P:positive regulation of cardiac epithelial to mesenchymal transition; ISS: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:RGD.
DR GO; GO:2001046; P:positive regulation of integrin-mediated signaling pathway; ISO:RGD.
DR GO; GO:0034394; P:protein localization to cell surface; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0001952; P:regulation of cell-matrix adhesion; ISO:RGD.
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; ISS: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 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Golgi apparatus; Membrane; Nucleus;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..172
FT /note="Epithelial membrane protein 2"
FT /id="PRO_0000430724"
FT TRANSMEM 1..21
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..168
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
SQ SEQUENCE 172 AA; 19649 MW; 2786C2686BDDBE2E CRC64;
MLVILAFIIV FHIVSTALLF ISTIDNAWWV GDGFSADIWR VCTNSTNCTE INDLSSTEEF
SGYSVMQAVQ ATMILSTILS CISFLIFLLQ LFRLKQGERF VLTAIIQLMS CLCVMIGASV
YTDRRQDLHH QNSQLYYLLQ EGSYGYSFIL AWVAFAFTFI SGLMYMILRK RK
