Reviewed, UniProtKB/Swiss-Prot Q9H173 (SIL1_HUMAN)

Names and origin

Protein names

Recommended name:
Nucleotide exchange factor SIL1

Alternative name(s):
BiP-associated protein
Short name=BAP

Gene names

Name:	SIL1
ORF Names:	UNQ545/PRO836

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	461 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for protein translocation and folding in the endoplasmic reticulum (ER). Functions as a nucleotide exchange factor for the ER lumenal chaperone HSPA5. Ref.2
Subunit structure	Interacts with HSPA5. Ref.2
Subcellular location	Endoplasmic reticulum lumen Ref.2 Ref.6.
Tissue specificity	Highly expressed in tissues which produce large amounts of secreted proteins such as kidney, liver and placenta. Also expressed in colon, heart, lung, ovary, pancreas, peripheral leukocyte, prostate, spleen and thymus. Expressed at low levels throughout the brain. Ref.2 Ref.6
Developmental stage	Expressed in fetal kidney, fetal lung, fetal liver and at low levels in fetal brain. Ref.6
Post-translational modification	N-glycosylated. Ref.2 Ref.8
Involvement in disease	Defects in SIL1 are a cause of Marinesco-Sjoegren syndrome (MSS) [MIM:248800]. MSS is an autosomal recessive multisystem disorder which is characterized by cerebellar ataxia due to cerebellar atrophy, with Purkinje and granule cell loss and myopathy featuring marked muscle replacement with fat and connective tissue. Other cardinal features include bilateral cataracts, hypergonadotrophic hypogonadism and mild to severe mental retardation. Skeletal abnormalities, short stature, dysarthria, strabismus and nystagmus are also frequent findings. Mutational inactivation of this protein may result in ER stress-induced cell death signaling or malfunctioning chaperone machineries that mishandle client proteins which are critical for the organs targeted in MSS. Ref.6 Ref.7
Sequence similarities	Belongs to the SIL1 family.

Ontologies

Keywords
Biological process	Protein transport Translocation Transport
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	intracellular protein transport Ref.1 Non-traceable author statement. Source: UniProtKB protein folding Ref.1 Non-traceable author statement. Source: UniProtKB transmembrane transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	unfolded protein binding Ref.1 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Potential
	Chain	32 – 461	430	Nucleotide exchange factor SIL1		PRO_0000223354
Regions
	Region	1 – 256	256	Interaction with HSPA5 and localization to the endoplasmic reticulum By similarity
Amino acid modifications
	Glycosylation	193	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	236	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	80	1	Q → R: dbSNP rs35581768.		VAR_034495
Experimental info
	Sequence conflict	57	1	K → E in BAC11096. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q9H173-1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: C4DD7E880A610880	FASTA	461	52,085
	10 20 30 40 50 60 MAPQSLPSSR MAPLGMLLGL LMAACFTFCL SHQNLKEFAL TNPEKSSTKE TERKETKAEE 70 80 90 100 110 120 ELDAEVLEVF HPTHEWQALQ PGQAVPAGSH VRLNLQTGER EAKLQYEDKF RNNLKGKRLD 130 140 150 160 170 180 INTNTYTSQD LKSALAKFKE GAEMESSKED KARQAEVKRL FRPIEELKKD FDELNVVIET 190 200 210 220 230 240 DMQIMVRLIN KFNSSSSSLE EKIAALFDLE YYVHQMDNAQ DLLSFGGLQV VINGLNSTEP 250 260 270 280 290 300 LVKEYAAFVL GAAFSSNPKV QVEAIEGGAL QKLLVILATE QPLTAKKKVL FALCSLLRHF 310 320 330 340 350 360 PYAQRQFLKL GGLQVLRTLV QEKGTEVLAV RVVTLLYDLV TEKMFAEEEA ELTQEMSPEK 370 380 390 400 410 420 LQQYRQVHLL PGLWEQGWCE ITAHLLALPE HDAREKVLQT LGVLLTTCRD RYRQDPQLGR 430 440 450 460 TLASLQAEYQ VLASLELQDG EDEGYFQELL GSVNSLLKEL R

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LHS1 and SIL1 provide a lumenal function that is essential for protein translocation into the endoplasmic reticulum." Tyson J.R., Stirling C.J. EMBO J. 19:6440-6452(2000) [PubMed: 11101517] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"BAP, a mammalian BiP-associated protein, is a nucleotide exchange factor that regulates the ATPase activity of BiP." Chung K.T., Shen Y., Hendershot L.M. J. Biol. Chem. 277:47557-47563(2002) [PubMed: 12356756] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH HSPA5, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed: 16303743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Embryo and Placenta.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[6]	"The gene disrupted in Marinesco-Sjoegren syndrome encodes SIL1, an HSPA5 cochaperone." Anttonen A.-K., Mahjneh I., Haemaelaeinen R.H., Lagier-Tourenne C., Kopra O., Waris L., Anttonen M., Joensuu T., Kalimo H., Paetau A., Tranebjaerg L., Chaigne D., Koenig M., Eeg-Olofsson O., Udd B., Somer M., Somer H., Lehesjoki A.-E. Nat. Genet. 37:1309-1311(2005) [PubMed: 16282978] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INVOLVEMENT IN MSS.
[7]	"Mutations in SIL1 cause Marinesco-Sjoegren syndrome, a cerebellar ataxia with cataract and myopathy." Senderek J., Krieger M., Stendel C., Bergmann C., Moser M., Breitbach-Faller N., Rudnik-Schoeneborn S., Blaschek A., Wolf N.I., Harting I., North K., Smith J., Muntoni F., Brockington M., Quijano-Roy S., Renault F., Herrmann R., Hendershot L.M. , Schroeder J.M., Lochmueller H., Topaloglu H., Voit T., Weis J., Ebinger F., Zerres K. Nat. Genet. 37:1312-1314(2005) [PubMed: 16282977] [Abstract] Cited for: INVOLVEMENT IN MSS.
[8]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-193, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ299442 mRNA. Translation: CAC17773.1. AF547994 mRNA. Translation: AAN84477.1. AY358950 mRNA. Translation: AAQ89309.1. AK074624 mRNA. Translation: BAC11096.1. AK075177 mRNA. Translation: BAC11452.1. BC011568 mRNA. Translation: AAH11568.1.
IPI	IPI00296197.
RefSeq	NP_001032722.1. NP_071909.1.
UniGene	Hs.483521
3D structure databases
SMR	Q9H173. Positions 151-459.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9H173.
Proteomic databases
PRIDE	Q9H173.
Genome annotation databases
Ensembl	ENST00000265195; ENSP00000265195; ENSG00000120725; Homo sapiens. [Genome view] ENST00000394817; ENSP00000378294; ENSG00000120725; Homo sapiens. [Genome view]
GeneID	64374.
KEGG	hsa:64374.
UCSC	uc003ldm.1. human.
Organism-specific databases
CTD	64374.
GeneCards	GC05M138310.
H-InvDB	HIX0005218.
HGNC	HGNC:24624. SIL1.
HPA	HPA011949.
MIM	248800. phenotype. 608005. gene.
Orphanet	559. Marinesco-Sjogren syndrome.
PharmGKB	PA142670916.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12840.
HOGENOM	HBG717681.
HOVERGEN	HBG093955.
InParanoid	Q9H173.
OMA	LREQGWC.
OrthoDB	EOG9SR0GD.
PhylomeDB	Q9H173.
Gene expression databases
ArrayExpress	Q9H173.
Bgee	Q9H173.
CleanEx	HS_SIL1.
Genevestigator	Q9H173.
GermOnline	ENSG00000120725. Homo sapiens.
Family and domain databases
InterPro	IPR011989. ARM-like. IPR016024. ARM-type_fold. [Graphical view]
Gene3D	G3DSA:1.25.10.10. ARM-like. 1 hit.
SUPFAM	SSF48371. ARM-type_fold. 1 hit.
ProtoNet	Search...
Other Resources
NextBio	66295.
SOURCE	Search...

Entry information

Entry name

SIL1_HUMAN

Accession

Primary (citable) accession number: Q9H173
Secondary accession number(s): Q8N2L3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2006
Last sequence update:	March 1, 2001
Last modified:	March 2, 2010
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.