ITM2C_MOUSE
ID ITM2C_MOUSE Reviewed; 269 AA.
AC Q91VK4; Q9JI06; Q9JME8;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Integral membrane protein 2C;
DE AltName: Full=Transmembrane protein BRI3;
DE Contains:
DE RecName: Full=CT-BRI3;
GN Name=Itm2c;
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].
RC TISSUE=Embryo;
RX PubMed=10679242; DOI=10.1006/bbrc.2000.2170;
RA Inoue S., Sano H., Ohta M.;
RT "Growth suppression of Escherichia coli by induction of expression of
RT mammalian genes with transmembrane or ATPase domains.";
RL Biochem. Biophys. Res. Commun. 268:553-561(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11290423; DOI=10.1016/s0378-1119(01)00374-2;
RA Vidal R., Calero M., Revesz T., Plant G., Ghiso J., Frangione B.;
RT "Sequence, genomic structure and tissue expression of human BRI3, a member
RT of the BRI gene family.";
RL Gene 266:95-102(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ICR;
RX PubMed=11804340;
RA Choi S.C., Kim J., Kim T.H., Cho S.Y., Park S.S., Kim K.D., Lee S.H.;
RT "Cloning and characterization of a type II integral transmembrane protein
RT gene, Itm2c, that is highly expressed in the mouse brain.";
RL Mol. Cells 12:391-397(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14592447; DOI=10.1016/j.bbrc.2003.10.038;
RA Wu H., Liu G., Li C., Zhao S.;
RT "bri3, a novel gene, participates in tumor necrosis factor-alpha-induced
RT cell death.";
RL Biochem. Biophys. Res. Commun. 311:518-524(2003).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=15606899; DOI=10.1111/j.1471-4159.2004.02840.x;
RA Wickham L., Benjannet S., Marcinkiewicz E., Chretien M., Seidah N.G.;
RT "Beta-amyloid protein converting enzyme 1 and brain-specific type II
RT membrane protein BRI3: binding partners processed by furin.";
RL J. Neurochem. 92:93-102(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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).
CC -!- FUNCTION: Negative regulator of amyloid-beta peptide production. May
CC inhibit the processing of APP by blocking its access to alpha- and
CC beta-secretase. Binding to the beta-secretase-cleaved APP C-terminal
CC fragment is negligible, suggesting that ITM2C is a poor gamma-secretase
CC cleavage inhibitor. May play a role in TNF-induced cell death and
CC neuronal differentiation. {ECO:0000269|PubMed:14592447}.
CC -!- SUBUNIT: Interacts with BACE1. Interacts with APP. Interacts with STMN2
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:14592447};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:14592447}.
CC Cell membrane {ECO:0000250}; Single-pass type II membrane protein
CC {ECO:0000250}.
CC -!- PTM: Type I membrane-bound, as well as soluble, furin has a pre-eminent
CC role in ITM2C proteolytic processing. PCSK7 and PCSK5 may also be
CC involved although to a lesser extent. The soluble form of PCSK7 is
CC incapable of processing ITM2C. Fails to undergo shedding by ADAM10 and
CC intramembrane cleavage by SPPL2B (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the ITM2 family. {ECO:0000305}.
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DR EMBL; AB030199; BAA92762.1; -; mRNA.
DR EMBL; AF272044; AAF89493.1; -; mRNA.
DR EMBL; AF282981; AAK00277.1; -; mRNA.
DR EMBL; AK036377; BAC29403.1; -; mRNA.
DR EMBL; BC012952; AAH12952.1; -; mRNA.
DR CCDS; CCDS35641.1; -.
DR RefSeq; NP_071862.2; NM_022417.3.
DR AlphaFoldDB; Q91VK4; -.
DR SMR; Q91VK4; -.
DR BioGRID; 211056; 3.
DR STRING; 10090.ENSMUSP00000027425; -.
DR GlyGen; Q91VK4; 1 site.
DR iPTMnet; Q91VK4; -.
DR PhosphoSitePlus; Q91VK4; -.
DR SwissPalm; Q91VK4; -.
DR EPD; Q91VK4; -.
DR MaxQB; Q91VK4; -.
DR PaxDb; Q91VK4; -.
DR PeptideAtlas; Q91VK4; -.
DR PRIDE; Q91VK4; -.
DR ProteomicsDB; 269416; -.
DR Antibodypedia; 34409; 161 antibodies from 20 providers.
DR DNASU; 64294; -.
DR Ensembl; ENSMUST00000027425; ENSMUSP00000027425; ENSMUSG00000026223.
DR GeneID; 64294; -.
DR KEGG; mmu:64294; -.
DR UCSC; uc011wof.1; mouse.
DR CTD; 81618; -.
DR MGI; MGI:1927594; Itm2c.
DR VEuPathDB; HostDB:ENSMUSG00000026223; -.
DR eggNOG; KOG4681; Eukaryota.
DR GeneTree; ENSGT00950000183115; -.
DR HOGENOM; CLU_074596_0_0_1; -.
DR InParanoid; Q91VK4; -.
DR OMA; ARTRMEL; -.
DR OrthoDB; 1322680at2759; -.
DR PhylomeDB; Q91VK4; -.
DR TreeFam; TF317770; -.
DR BioGRID-ORCS; 64294; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Itm2c; mouse.
DR PRO; PR:Q91VK4; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q91VK4; protein.
DR Bgee; ENSMUSG00000026223; Expressed in olfactory tubercle and 264 other tissues.
DR ExpressionAtlas; Q91VK4; baseline and differential.
DR Genevisible; Q91VK4; MM.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:MGI.
DR GO; GO:0042985; P:negative regulation of amyloid precursor protein biosynthetic process; IBA:GO_Central.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:MGI.
DR GO; GO:0030182; P:neuron differentiation; ISO:MGI.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR InterPro; IPR007084; BRICHOS_dom.
DR InterPro; IPR040145; ITM2.
DR PANTHER; PTHR10962; PTHR10962; 1.
DR Pfam; PF04089; BRICHOS; 1.
DR SMART; SM01039; BRICHOS; 1.
DR PROSITE; PS50869; BRICHOS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cleavage on pair of basic residues; Disulfide bond;
KW Glycoprotein; Lysosome; Membrane; Phosphoprotein; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..269
FT /note="Integral membrane protein 2C"
FT /id="PRO_0000154827"
FT PEPTIDE 244..269
FT /note="CT-BRI3"
FT /id="PRO_0000232646"
FT TRANSMEM 57..77
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT DOMAIN 138..232
FT /note="BRICHOS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00255"
FT SITE 243..244
FT /note="Cleavage; by furin"
FT /evidence="ECO:0000250"
FT MOD_RES 39
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5PQL7"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 165..224
FT /evidence="ECO:0000250"
FT CONFLICT 12
FT /note="Missing (in Ref. 1; BAA92762)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="G -> A (in Ref. 5; AAH12952)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 269 AA; 30482 MW; B949E6E05EA65502 CRC64;
MVKISFQPAV AGIKADKADK AAASGPASAS APAAEILLTP AREERPPRHR SRKGGSVGGV
CYLSMGMVVL LMGLVFASVY IYRYFFLAQL ARDNFFHCGV LYEDSLSSQI RTRLELEEDV
KIYLEENYER INVPVPQFGG GDPADIIHDF QRGLTAYHDI SLDKCYVIEL NTTIVLPPRN
FWELLMNVKR GTYLPQTYII QEEMVVTEHV RDKEALGSFI YHLCNGKDTY RLRRRSTRRR
INKRGGKNCN AIRHFENTFV VETLICGVV
