SIL1_MOUSE
ID SIL1_MOUSE Reviewed; 465 AA.
AC Q9EPK6; Q91V34;
DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2006, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Nucleotide exchange factor SIL1;
DE Flags: Precursor;
GN Name=Sil1;
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=11101517; DOI=10.1093/emboj/19.23.6440;
RA Tyson J.R., Stirling C.J.;
RT "LHS1 and SIL1 provide a lumenal function that is essential for protein
RT translocation into the endoplasmic reticulum.";
RL EMBO J. 19:6440-6452(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [4]
RP INTERACTION WITH HSPA5, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16116427; DOI=10.1038/ng1620;
RA Zhao L., Longo-Guess C., Harris B.S., Lee J.-W., Ackerman S.L.;
RT "Protein accumulation and neurodegeneration in the woozy mutant mouse is
RT caused by disruption of SIL1, a cochaperone of BiP.";
RL Nat. Genet. 37:974-979(2005).
RN [5]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=16282978; DOI=10.1038/ng1677;
RA Anttonen A.-K., Mahjneh I., Haemaelaeinen R.H., Lagier-Tourenne C.,
RA Kopra O., Waris L., Anttonen M., Joensuu T., Kalimo H., Paetau A.,
RA Tranebjaerg L., Chaigne D., Koenig M., Eeg-Olofsson O., Udd B., Somer M.,
RA Somer H., Lehesjoki A.-E.;
RT "The gene disrupted in Marinesco-Sjoegren syndrome encodes SIL1, an HSPA5
RT cochaperone.";
RL Nat. Genet. 37:1309-1311(2005).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=16282977; DOI=10.1038/ng1678;
RA Senderek J., Krieger M., Stendel C., Bergmann C., Moser M.,
RA Breitbach-Faller N., Rudnik-Schoeneborn S., Blaschek A., Wolf N.I.,
RA Harting I., North K., Smith J., Muntoni F., Brockington M., Quijano-Roy S.,
RA Renault F., Herrmann R., Hendershot L.M., Schroeder J.M., Lochmueller H.,
RA Topaloglu H., Voit T., Weis J., Ebinger F., Zerres K.;
RT "Mutations in SIL1 cause Marinesco-Sjoegren syndrome, a cerebellar ataxia
RT with cataract and myopathy.";
RL Nat. Genet. 37:1312-1314(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Pancreas, 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).
CC -!- FUNCTION: Required for protein translocation and folding in the
CC endoplasmic reticulum (ER). Functions as a nucleotide exchange factor
CC for the ER lumenal chaperone HSPA5. {ECO:0000250|UniProtKB:Q9H173}.
CC -!- SUBUNIT: Interacts with HSPA5. {ECO:0000269|PubMed:16116427}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:16116427}.
CC -!- TISSUE SPECIFICITY: Expressed in several areas of the brain including
CC the cerebellum, cerebral cortex, cortical neurons, glial cells of white
CC matter, hippocampus, olfactory bulb, Purkinje cells, inferior olive and
CC the choroids plexus. Also expressed in the eye and skeletal muscle.
CC {ECO:0000269|PubMed:16116427, ECO:0000269|PubMed:16282977,
CC ECO:0000269|PubMed:16282978}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing retina and epithelial
CC cells of the lens at 12.5 dpc. Expressed in the developing cerebral
CC cortex at 15.5 dpc. {ECO:0000269|PubMed:16282978}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9H173}.
CC -!- PTM: Ubiquitinated by the CRL2(FEM1A) and CRL2(FEM1C) complexes, which
CC recognize the -Lys-Xaa-Xaa-Arg C-degron at the C-terminus, leading to
CC its degradation. {ECO:0000250|UniProtKB:Q9H173}.
CC -!- DISRUPTION PHENOTYPE: Mice develop adult-onset ataxia with cerebellar
CC Purkinje cell loss. Affected cells have intracellular protein
CC accumulations in the endoplasmic reticulum and the nucleus.
CC {ECO:0000269|PubMed:16282978}.
CC -!- SIMILARITY: Belongs to the SIL1 family. {ECO:0000305}.
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DR EMBL; AJ297884; CAC17789.1; -; mRNA.
DR EMBL; AK170415; BAE41781.1; -; mRNA.
DR EMBL; BC016119; AAH16119.1; -; mRNA.
DR EMBL; BC016466; AAH16466.1; -; mRNA.
DR CCDS; CCDS29140.1; -.
DR RefSeq; NP_109674.2; NM_030749.2.
DR RefSeq; XP_006526428.1; XM_006526365.3.
DR RefSeq; XP_006526429.1; XM_006526366.3.
DR RefSeq; XP_011245345.1; XM_011247043.2.
DR AlphaFoldDB; Q9EPK6; -.
DR SMR; Q9EPK6; -.
DR BioGRID; 219881; 3.
DR STRING; 10090.ENSMUSP00000025215; -.
DR GlyConnect; 2568; 3 N-Linked glycans (1 site).
DR GlyGen; Q9EPK6; 2 sites, 3 N-linked glycans (1 site).
DR iPTMnet; Q9EPK6; -.
DR PhosphoSitePlus; Q9EPK6; -.
DR SwissPalm; Q9EPK6; -.
DR EPD; Q9EPK6; -.
DR MaxQB; Q9EPK6; -.
DR PaxDb; Q9EPK6; -.
DR PeptideAtlas; Q9EPK6; -.
DR PRIDE; Q9EPK6; -.
DR ProteomicsDB; 261043; -.
DR Antibodypedia; 2386; 325 antibodies from 33 providers.
DR Ensembl; ENSMUST00000025215; ENSMUSP00000025215; ENSMUSG00000024357.
DR GeneID; 81500; -.
DR KEGG; mmu:81500; -.
DR UCSC; uc008emc.2; mouse.
DR CTD; 64374; -.
DR MGI; MGI:1932040; Sil1.
DR VEuPathDB; HostDB:ENSMUSG00000024357; -.
DR eggNOG; KOG2160; Eukaryota.
DR GeneTree; ENSGT00940000153909; -.
DR HOGENOM; CLU_046547_1_0_1; -.
DR InParanoid; Q9EPK6; -.
DR OMA; FQPTHEW; -.
DR OrthoDB; 1501690at2759; -.
DR PhylomeDB; Q9EPK6; -.
DR TreeFam; TF324307; -.
DR BioGRID-ORCS; 81500; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Sil1; mouse.
DR PRO; PR:Q9EPK6; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9EPK6; protein.
DR Bgee; ENSMUSG00000024357; Expressed in spermatocyte and 244 other tissues.
DR ExpressionAtlas; Q9EPK6; baseline and differential.
DR Genevisible; Q9EPK6; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0000774; F:adenyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR Gene3D; 1.25.10.10; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR SUPFAM; SSF48371; SSF48371; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Protein transport; Reference proteome;
KW Signal; Translocation; Transport; Ubl conjugation.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..465
FT /note="Nucleotide exchange factor SIL1"
FT /id="PRO_0000223355"
FT REGION 1..260
FT /note="Interaction with HSPA5 and localization to the
FT endoplasmic reticulum"
FT /evidence="ECO:0000269|PubMed:16116427"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 143
FT /note="K -> T (in Ref. 1; CAC17789)"
FT /evidence="ECO:0000305"
FT CONFLICT 152
FT /note="K -> Q (in Ref. 1; CAC17789)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 465 AA; 52430 MW; C3E2DB44394F1161 CRC64;
MAPQHLPSTR MASPGMLLGL LLTSCLTLCL SCQNSNNFAL TNPEKSIHQE SDTKETREEE
ELDTEILEVF HPTQEWQTLQ PGQAVPAGSH VRMNLQTGVN EVKLQQEDKF QNNLKGFKRG
RRLDINANTY TSQDLKSALA KFKEGTEMEN SKDELARQAT VKQLFRPIEE LKKEFDELNV
VLETDMQIMV RLINKFNSSS SSLEEKVAAL FDLEYYVHQM DNAQDLLSFG GLQVVINGLN
STEPLVKEYA AFVLGAAFSS NPKVQVEAIE GGALQKLLVI LATNQPLPAK KKVLFALCSL
LRHFPYAQQQ FLKLGGLQVL RSLVQEKSAK VLAVRVVTLL YDLVTEKMFA EEEAELTQDS
SPEKLQQYRQ VQLLPGLQEQ GWCEITAQLL ALPEHDAREK VLQTLGALLT TCRDRYRQDL
QLSRTLGRLQ AEYQALASLE LQEGEDDGYF RELLASINSL MKELR
