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   24-JAN-2024, entry version 149.
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; 4.
DR   STRING; 10090.ENSMUSP00000025215; -.
DR   GlyConnect; 2568; 3 N-Linked glycans (1 site).
DR   GlyCosmos; Q9EPK6; 2 sites, 3 glycans.
DR   GlyGen; Q9EPK6; 3 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; Q9EPK6; -.
DR   PhosphoSitePlus; Q9EPK6; -.
DR   SwissPalm; Q9EPK6; -.
DR   EPD; Q9EPK6; -.
DR   MaxQB; Q9EPK6; -.
DR   PaxDb; 10090-ENSMUSP00000025215; -.
DR   PeptideAtlas; Q9EPK6; -.
DR   ProteomicsDB; 261043; -.
DR   Pumba; Q9EPK6; -.
DR   Antibodypedia; 2386; 362 antibodies from 33 providers.
DR   Ensembl; ENSMUST00000025215.10; ENSMUSP00000025215.9; ENSMUSG00000024357.11.
DR   GeneID; 81500; -.
DR   KEGG; mmu:81500; -.
DR   UCSC; uc008emc.2; mouse.
DR   AGR; MGI:1932040; -.
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; 67078at2759; -.
DR   PhylomeDB; Q9EPK6; -.
DR   TreeFam; TF324307; -.
DR   BioGRID-ORCS; 81500; 2 hits in 77 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 247 other cell types or tissues.
DR   ExpressionAtlas; Q9EPK6; baseline and differential.
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; Leucine-rich Repeat Variant; 1.
DR   InterPro; IPR011989; ARM-like.
DR   InterPro; IPR016024; ARM-type_fold.
DR   PANTHER; PTHR19316:SF35; NUCLEOTIDE EXCHANGE FACTOR SIL1; 1.
DR   PANTHER; PTHR19316; PROTEIN FOLDING REGULATOR; 1.
DR   SUPFAM; SSF48371; ARM repeat; 1.
DR   Genevisible; Q9EPK6; MM.
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
//