EDEM2_MOUSE
ID EDEM2_MOUSE Reviewed; 577 AA.
AC Q8BJT9; Q8BJR2; Q8BK85; Q91VV3;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=ER degradation-enhancing alpha-mannosidase-like protein 2 {ECO:0000303|PubMed:15579471};
DE Flags: Precursor;
GN Name=Edem2 {ECO:0000303|PubMed:15579471, ECO:0000312|MGI:MGI:1915540};
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 {ECO:0000312|EMBL:BAC37599.1};
RN [1] {ECO:0000312|EMBL:BAC37599.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Urinary bladder;
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 [2]
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 [3] {ECO:0000312|EMBL:EDL06140.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [4] {ECO:0000312|EMBL:AAH08268.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor {ECO:0000312|EMBL:AAH08268.1};
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] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND GLYCOSYLATION.
RX PubMed=15579471; DOI=10.1074/jbc.c400534200;
RA Olivari S., Galli C., Alanen H., Ruddock L., Molinari M.;
RT "A novel stress-induced EDEM variant regulating endoplasmic reticulum-
RT associated glycoprotein degradation.";
RL J. Biol. Chem. 280:2424-2428(2005).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=25655076; DOI=10.1186/s12860-015-0047-7;
RA Sokolowska I., Pilka E.S., Sandvig K., Wegrzyn G., Slominska-Wojewodzka M.;
RT "Hydrophobicity of protein determinants influences the recognition of
RT substrates by EDEM1 and EDEM2 in human cells.";
RL BMC Cell Biol. 16:1-1(2015).
CC -!- FUNCTION: Involved in the endoplasmic reticulum-associated degradation
CC (ERAD) pathway that targets misfolded glycoproteins for degradation in
CC an N-glycan-dependent manner (PubMed:15579471, PubMed:25655076). May
CC initiate ERAD by promoting the first mannose trimming step of ERAD
CC substrates, from Man9GlcNAc2 to Man8GlcNAc2 (By similarity). Seems to
CC recognize and bind to exposed hydrophobic regions in target proteins
CC (PubMed:25655076). {ECO:0000250|UniProtKB:Q9BV94,
CC ECO:0000269|PubMed:15579471, ECO:0000269|PubMed:25655076}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:15579471}.
CC -!- INDUCTION: Up-regulated by the unfolded protein response (UPR) via the
CC XBP1 transcription factor. {ECO:0000269|PubMed:15579471}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15579471}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 47 family.
CC {ECO:0000255|RuleBase:RU361193}.
CC -!- CAUTION: Has similarity to alpha 1,2-mannosidases, but the catalytic
CC activity of this protein is controversial. One study shows that it is
CC important for a specific oligosaccharide trimming step from Man9GlcNAc2
CC to Man8GlcNAc2, suggesting activity as a mannosidase. However, another
CC study reports that this protein has no mannosidase activity.
CC {ECO:0000250|UniProtKB:Q9BV94}.
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DR EMBL; AK075650; BAC35880.1; -; mRNA.
DR EMBL; AK079296; BAC37599.1; -; mRNA.
DR EMBL; AK080636; BAC37968.1; -; mRNA.
DR EMBL; AK155024; BAE32997.1; -; mRNA.
DR EMBL; AK166998; BAE39177.1; -; mRNA.
DR EMBL; AL929233; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466551; EDL06140.1; -; Genomic_DNA.
DR EMBL; BC008268; AAH08268.1; -; mRNA.
DR CCDS; CCDS16953.1; -.
DR RefSeq; NP_663512.2; NM_145537.2.
DR AlphaFoldDB; Q8BJT9; -.
DR SMR; Q8BJT9; -.
DR IntAct; Q8BJT9; 8.
DR STRING; 10090.ENSMUSP00000041202; -.
DR CAZy; GH47; Glycoside Hydrolase Family 47.
DR GlyGen; Q8BJT9; 4 sites.
DR PhosphoSitePlus; Q8BJT9; -.
DR MaxQB; Q8BJT9; -.
DR PaxDb; Q8BJT9; -.
DR PRIDE; Q8BJT9; -.
DR ProteomicsDB; 341187; -.
DR Antibodypedia; 25993; 147 antibodies from 29 providers.
DR DNASU; 108687; -.
DR Ensembl; ENSMUST00000040833; ENSMUSP00000041202; ENSMUSG00000038312.
DR GeneID; 108687; -.
DR KEGG; mmu:108687; -.
DR UCSC; uc008nlg.2; mouse.
DR CTD; 55741; -.
DR MGI; MGI:1915540; Edem2.
DR VEuPathDB; HostDB:ENSMUSG00000038312; -.
DR eggNOG; KOG2429; Eukaryota.
DR GeneTree; ENSGT00940000159233; -.
DR HOGENOM; CLU_003818_5_4_1; -.
DR InParanoid; Q8BJT9; -.
DR OMA; DWHLWVS; -.
DR OrthoDB; 434316at2759; -.
DR PhylomeDB; Q8BJT9; -.
DR TreeFam; TF300807; -.
DR BioGRID-ORCS; 108687; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Edem2; mouse.
DR PRO; PR:Q8BJT9; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8BJT9; protein.
DR Bgee; ENSMUSG00000038312; Expressed in lacrimal gland and 238 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IEA:GOC.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004571; F:mannosyl-oligosaccharide 1,2-alpha-mannosidase activity; IEA:Ensembl.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:1904380; P:endoplasmic reticulum mannose trimming; IBA:GO_Central.
DR GO; GO:1904382; P:mannose trimming involved in glycoprotein ERAD pathway; ISO:MGI.
DR GO; GO:1904154; P:positive regulation of retrograde protein transport, ER to cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR GO; GO:0036509; P:trimming of terminal mannose on B branch; ISO:MGI.
DR GO; GO:0097466; P:ubiquitin-dependent glycoprotein ERAD pathway; ISO:MGI.
DR Gene3D; 1.50.10.10; -; 1.
DR InterPro; IPR012341; 6hp_glycosidase-like_sf.
DR InterPro; IPR044674; EDEM1/2/3.
DR InterPro; IPR001382; Glyco_hydro_47.
DR InterPro; IPR036026; Seven-hairpin_glycosidases.
DR PANTHER; PTHR45679; PTHR45679; 1.
DR Pfam; PF01532; Glyco_hydro_47; 1.
DR PRINTS; PR00747; GLYHDRLASE47.
DR SUPFAM; SSF48225; SSF48225; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Reference proteome; Signal;
KW Unfolded protein response.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..577
FT /note="ER degradation-enhancing alpha-mannosidase-like
FT protein 2"
FT /id="PRO_5014588821"
FT REGION 513..561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 523..561
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000255|PROSITE-
FT ProRule:PRU00498"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 450
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CONFLICT 505
FT /note="F -> L (in Ref. 1; BAC37968)"
FT /evidence="ECO:0000305"
FT CONFLICT 536
FT /note="S -> F (in Ref. 4; AAH08268)"
FT /evidence="ECO:0000305"
FT CONFLICT 549
FT /note="Q -> R (in Ref. 4; AAH08268)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="L -> V (in Ref. 1; BAC35880)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 577 AA; 64610 MW; 3B6992FE87F17ED9 CRC64;
MPFRLLIPLG LVCVLLPLHH GAPGPDGTAP DPAHYRERVK AMFYHAYDSY LENAFPYDEL
RPLTCDGHDT WGSFSLTLID ALDTLLILGN TSEFQRVVEV LQDNVDFDID VNASVFETNI
RVVGGLLSAH LLSKKAGVEV EAGWPCSGPL LRMAEEAARK LLPAFQTPTG MPYGTVNLLH
GVNPGETPVT CTAGIGTFIV EFATLSSLTG DPVFEDVARV ALMRLWESRS DIGLVGNHID
VLTGKWVAQD AGIGAGVDSY FEYLVKGAIL LQDKKLMAMF LEYNKAIRNY THFDDWYLWV
QMYKGTVSMP VFQSLEAYWP GLQSLIGDID NAMRTFLNYY TVWKQFGGLP EFYNIPQGYT
VEKREGYPLR PELIESAMYL YRATGDPTLL ELGRDAVESI EKISKVECGF ATIKDLRDHK
LDNRMESFFL AETVKYLYLL FHPNNFIHNN GSTFDSVMTP HGECILGAGG YIFNTEAHPI
DPAALHCCRR LKEEQWEVED LIKEFYSLKQ SRPKRAQRKT VRSGPWEPQS GPATLSSPAN
QPREKQPAQQ RTPLLSCPSQ PFTSKLALLG QVFLDSS
