ID   SIL1_HUMAN              Reviewed;         461 AA.
AC   Q9H173; Q8N2L3;
DT   21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   03-NOV-2009, entry version 62.
DE   RecName: Full=Nucleotide exchange factor SIL1;
DE   AltName: Full=BiP-associated protein;
DE            Short=BAP;
DE   Flags: Precursor;
GN   Name=SIL1; ORFNames=UNQ545/PRO836;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=20553224; 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
RT   protein translocation into the endoplasmic reticulum.";
RL   EMBO J. 19:6440-6452(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH HSPA5,
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX   MEDLINE=22344675; PubMed=12356756; DOI=10.1074/jbc.M208377200;
RA   Chung K.T., Shen Y., Hendershot L.M.;
RT   "BAP, a mammalian BiP-associated protein, is a nucleotide exchange
RT   factor that regulates the ATPase activity of BiP.";
RL   J. Biol. Chem. 277:47557-47563(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   MEDLINE=22887296; PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo, and Placenta;
RX   PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA   Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA   Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA   Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA   Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA   Isogai T.;
RT   "Signal sequence and keyword trap in silico for selection of full-
RT   length human cDNAs encoding secretion or membrane proteins from oligo-
RT   capped cDNA libraries.";
RL   DNA Res. 12:117-126(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skin;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP   INVOLVEMENT IN MSS.
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.,
RA   Somer M., Somer H., Lehesjoki A.-E.;
RT   "The gene disrupted in Marinesco-Sjoegren syndrome encodes SIL1, an
RT   HSPA5 cochaperone.";
RL   Nat. Genet. 37:1309-1311(2005).
RN   [7]
RP   INVOLVEMENT IN MSS.
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.,
RA   Quijano-Roy S., Renault F., Herrmann R., Hendershot L.M.,
RA   Schroeder J.M., Lochmueller H., Topaloglu H., Voit T., Weis J.,
RA   Ebinger F., Zerres K.;
RT   "Mutations in SIL1 cause Marinesco-Sjoegren syndrome, a cerebellar
RT   ataxia with cataract and myopathy.";
RL   Nat. Genet. 37:1312-1314(2005).
RN   [8]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-193, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of
RT   multiple enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
CC   -!- FUNCTION: Required for protein translocation and folding in the
CC       endoplasmic reticulum (ER). Functions as a nucleotide exchange
CC       factor for the ER lumenal chaperone HSPA5.
CC   -!- SUBUNIT: Interacts with HSPA5.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
CC   -!- TISSUE SPECIFICITY: Highly expressed in tissues which produce
CC       large amounts of secreted proteins such as kidney, liver and
CC       placenta. Also expressed in colon, heart, lung, ovary, pancreas,
CC       peripheral leukocyte, prostate, spleen and thymus. Expressed at
CC       low levels throughout the brain.
CC   -!- DEVELOPMENTAL STAGE: Expressed in fetal kidney, fetal lung, fetal
CC       liver and at low levels in fetal brain.
CC   -!- PTM: N-glycosylated.
CC   -!- DISEASE: Defects in SIL1 are a cause of Marinesco-Sjoegren
CC       syndrome (MSS) [MIM:248800]. MSS is an autosomal recessive
CC       multisystem disorder which is characterized by cerebellar ataxia
CC       due to cerebellar atrophy, with Purkinje and granule cell loss and
CC       myopathy featuring marked muscle replacement with fat and
CC       connective tissue. Other cardinal features include bilateral
CC       cataracts, hypergonadotrophic hypogonadism and mild to severe
CC       mental retardation. Skeletal abnormalities, short stature,
CC       dysarthria, strabismus and nystagmus are also frequent findings.
CC       Mutational inactivation of this protein may result in ER stress-
CC       induced cell death signaling or malfunctioning chaperone
CC       machineries that mishandle client proteins which are critical for
CC       the organs targeted in MSS.
CC   -!- SIMILARITY: Belongs to the SIL1 family.
CC   -!- WEB RESOURCE: Name=GeneReviews;
CC       URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SIL1";
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DR   EMBL; AJ299442; CAC17773.1; -; mRNA.
DR   EMBL; AF547994; AAN84477.1; -; mRNA.
DR   EMBL; AY358950; AAQ89309.1; -; mRNA.
DR   EMBL; AK074624; BAC11096.1; -; mRNA.
DR   EMBL; AK075177; BAC11452.1; -; mRNA.
DR   EMBL; BC011568; AAH11568.1; -; mRNA.
DR   IPI; IPI00296197; -.
DR   RefSeq; NP_001032722.1; -.
DR   RefSeq; NP_071909.1; -.
DR   UniGene; Hs.483521; -.
DR   STRING; Q9H173; -.
DR   PRIDE; Q9H173; -.
DR   Ensembl; ENST00000265195; ENSP00000265195; ENSG00000120725; Homo sapiens.
DR   Ensembl; ENST00000394817; ENSP00000378294; ENSG00000120725; Homo sapiens.
DR   GeneID; 64374; -.
DR   KEGG; hsa:64374; -.
DR   UCSC; uc003ldm.1; human.
DR   CTD; 64374; -.
DR   GeneCards; GC05M138310; -.
DR   H-InvDB; HIX0005218; -.
DR   HGNC; HGNC:24624; SIL1.
DR   HPA; HPA011949; -.
DR   MIM; 248800; phenotype.
DR   MIM; 608005; gene.
DR   Orphanet; 559; Marinesco-Sjogren syndrome.
DR   PharmGKB; PA142670916; -.
DR   HOGENOM; Q9H173; -.
DR   HOVERGEN; Q9H173; -.
DR   OMA; LREQGWC; -.
DR   NextBio; 66295; -.
DR   ArrayExpress; Q9H173; -.
DR   Bgee; Q9H173; -.
DR   CleanEx; HS_SIL1; -.
DR   Genevestigator; Q9H173; -.
DR   GermOnline; ENSG00000120725; Homo sapiens.
DR   GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR   GO; GO:0051082; F:unfolded protein binding; NAS:UniProtKB.
DR   GO; GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
DR   GO; GO:0006457; P:protein folding; NAS:UniProtKB.
DR   GO; GO:0055085; P:transmembrane transport; IEA:UniProtKB-KW.
DR   InterPro; IPR011989; ARM-like.
DR   Gene3D; G3DSA:1.25.10.10; ARM-like; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Disease mutation; Endoplasmic reticulum;
KW   Glycoprotein; Polymorphism; Protein transport; Signal; Translocation;
KW   Transport.
FT   SIGNAL        1     31       Potential.
FT   CHAIN        32    461       Nucleotide exchange factor SIL1.
FT                                /FTId=PRO_0000223354.
FT   REGION        1    256       Interaction with HSPA5 and localization
FT                                to the endoplasmic reticulum (By
FT                                similarity).
FT   CARBOHYD    193    193       N-linked (GlcNAc...).
FT   CARBOHYD    236    236       N-linked (GlcNAc...) (Potential).
FT   VARIANT      80     80       Q -> R (in dbSNP:rs35581768).
FT                                /FTId=VAR_034495.
FT   CONFLICT     57     57       K -> E (in Ref. 4; BAC11096).
SQ   SEQUENCE   461 AA;  52085 MW;  C4DD7E880A610880 CRC64;
     MAPQSLPSSR MAPLGMLLGL LMAACFTFCL SHQNLKEFAL TNPEKSSTKE TERKETKAEE
     ELDAEVLEVF HPTHEWQALQ PGQAVPAGSH VRLNLQTGER EAKLQYEDKF RNNLKGKRLD
     INTNTYTSQD LKSALAKFKE GAEMESSKED KARQAEVKRL FRPIEELKKD FDELNVVIET
     DMQIMVRLIN KFNSSSSSLE EKIAALFDLE YYVHQMDNAQ DLLSFGGLQV VINGLNSTEP
     LVKEYAAFVL GAAFSSNPKV QVEAIEGGAL QKLLVILATE QPLTAKKKVL FALCSLLRHF
     PYAQRQFLKL GGLQVLRTLV QEKGTEVLAV RVVTLLYDLV TEKMFAEEEA ELTQEMSPEK
     LQQYRQVHLL PGLWEQGWCE ITAHLLALPE HDAREKVLQT LGVLLTTCRD RYRQDPQLGR
     TLASLQAEYQ VLASLELQDG EDEGYFQELL GSVNSLLKEL R
//