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SIL1 SIL1 nucleotide exchange factor [ Homo sapiens (human) ]

Gene ID: 64374, updated on 3-Apr-2024

Summary

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Official Symbol
SIL1provided by HGNC
Official Full Name
SIL1 nucleotide exchange factorprovided by HGNC
Primary source
HGNC:HGNC:24624
See related
Ensembl:ENSG00000120725 MIM:608005; AllianceGenome:HGNC:24624
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
BAP; MSS; ULG5
Summary
This gene encodes a resident endoplasmic reticulum (ER), N-linked glycoprotein with an N-terminal ER targeting sequence, 2 putative N-glycosylation sites, and a C-terminal ER retention signal. This protein functions as a nucleotide exchange factor for another unfolded protein response protein. Mutations in this gene have been associated with Marinesco-Sjogren syndrome. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in testis (RPKM 23.5), thyroid (RPKM 19.7) and 25 other tissues See more
Orthologs
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Genomic context

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See SIL1 in Genome Data Viewer
Location:
5q31.2
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (138946724..139198368, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (139472860..139724442, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (138282413..138534057, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:138089147-138089714 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:138089715-138090281 Neighboring gene CTNNA1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23216 Neighboring gene catenin alpha 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:138164188-138164688 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:138188550-138189082 Neighboring gene leucine rich repeat transmembrane neuronal 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:138279886-138280098 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:138284538-138285402 Neighboring gene uncharacterized LOC124901079 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:138289067-138290004 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:138346233-138346880 Neighboring gene uncharacterized LOC124901080 Neighboring gene RNA, 5S ribosomal pseudogene 194 Neighboring gene ribosomal protein L12 pseudogene 21 Neighboring gene MPRA-validated peak5496 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16405 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:138559318-138560164 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:138567539-138568038 Neighboring gene RNA, U6 small nuclear 572, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23217 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16406 Neighboring gene uncharacterized LOC124901081 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23218 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16407 Neighboring gene small nucleolar RNA, H/ACA box 74D Neighboring gene small nucleolar RNA host gene 4 Neighboring gene matrin 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Proteomic Analysis of Marinesco-Sjogren Syndrome Fibroblasts Indicates Pro-Survival Metabolic Adaptation to SIL1 Loss. Potenza F, et al. Int J Mol Sci, 2021 Nov 18. PMID 34830330, Free PMC Article
  2. Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis. Li ZF, et al. Sci Prog, 2020 Jan-Mar. PMID 31791191, Free PMC Article
  3. Marinesco-Sjögren Syndrome in an Emirati Child with a Novel Mutation in SIL1 Affecting the 5' Untranslated Region. Nair P, et al. Med Princ Pract, 2016. PMID 27544240, Free PMC Article
  4. Novel SIL1 nonstop mutation in a Chinese consanguineous family with Marinesco-Sjögren syndrome and Dandy-Walker syndrome. Gai N, et al. Clin Chim Acta, 2016 Jul 1. PMID 27106665
  5. Cellular Signature of SIL1 Depletion: Disease Pathogenesis due to Alterations in Protein Composition Beyond the ER Machinery. Roos A, et al. Mol Neurobiol, 2016 Oct. PMID 26468156

See all (69) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Down-Regulation and Clinic-Pathological Correlation of SIK-1 and SIL-1-LNC in Non-Small Cell Lung Cancer Patients.
    Title: Down-regulation and Clinic-pathological Correlation of SIK-1 and SIK-1-LNC in Non-small Cell Lung Cancer Patients.
  2. Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis.
    Title: Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis.
  3. Proteomic Analysis of Marinesco-Sjogren Syndrome Fibroblasts Indicates Pro-Survival Metabolic Adaptation to SIL1 Loss.
    Title: Proteomic Analysis of Marinesco-Sjogren Syndrome Fibroblasts Indicates Pro-Survival Metabolic Adaptation to SIL1 Loss.
  4. SIL1 deficiency causes degenerative changes of peripheral nerves and neuromuscular junctions in fish, mice and human. The data expand the spectrum of tissues affected by SIL1-loss and suggest that impaired neuromuscular transmission might be part of Marinesco-Sjogren Syndrome pathophysiology.
    Title: SIL1 deficiency causes degenerative changes of peripheral nerves and neuromuscular junctions in fish, mice and human.
  5. single-molecule FRET experiments with mammalian proteins reveal that Bap affects the conformation of both BiP domains, including the lid subdomain, which is important for substrate binding
    Title: Bap (Sil1) regulates the molecular chaperone BiP by coupling release of nucleotide and substrate.
  6. Findings indicate that SIL1 deficiency alters secretory transport, potentially contributing to the cellular pathology of Marinesco-Sjogren syndrome.
    Title: PERK inhibition attenuates the abnormalities of the secretory pathway and the increased apoptotic rate induced by SIL1 knockdown in HeLa cells.
  7. SIL1-depleted HEK293 cells are an appropriate model to identify proteins modulated by SIL1 expression level.
    Title: Cellular Signature of SIL1 Depletion: Disease Pathogenesis due to Alterations in Protein Composition Beyond the ER Machinery.
  8. In a child with Marinesco-Sjogren syndrome it was found that a mutation in SIL1 affected the 5' UTR, translation initiation site and the endoplasmic reticulum-targeting signal sequence.
    Title: Marinesco-Sjögren Syndrome in an Emirati Child with a Novel Mutation in SIL1 Affecting the 5' Untranslated Region.
  9. this case study is the first report on Chinese Marinesco-Sjogren syndrome (MSS) patients, MSS complicated by Dandy-Walker syndrome (DWS), and a nonstop mutation in SIL1; our findings imply the pathogenetic association between DWS and MSS
    Title: Novel SIL1 nonstop mutation in a Chinese consanguineous family with Marinesco-Sjögren syndrome and Dandy-Walker syndrome.
  10. Two NEFs, Grp170 and Sil1, trigger toxin release from BiP to enable successful retrotranslocation and clarify the fate of the toxin after it disengages from BiP.
    Title: The nucleotide exchange factors Grp170 and Sil1 induce cholera toxin release from BiP to enable retrotranslocation.
Submit: New GeneRIF Correction See all GeneRIFs (25)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Marinesco-Sjogren syndrome
MedGen: C0024814 OMIM: 248800 GeneReviews: Marinesco-Sjogren Syndrome
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Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with SIL1; predicted interaction to be within the endoplasmic reticulum and function as chaperone for endoplasmic reticulum-associated degradation PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables adenyl-nucleotide exchange factor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables adenyl-nucleotide exchange factor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables unfolded protein binding NAS
Non-traceable Author Statement
more info
 PubMed 
Process Evidence Code Pubs
involved_in cotranslational protein targeting to membrane ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in intracellular protein transport NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in protein folding NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum NAS
Non-traceable Author Statement
more info
 PubMed 
located_in endoplasmic reticulum lumen IEA
Inferred from Electronic Annotation
more info
  
located_in extracellular space HDA PubMed 

General protein information

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Preferred Names
nucleotide exchange factor SIL1
Names
BiP-associated protein
SIL1 homolog, endoplasmic reticulum chaperone
SIL1-like protein endoplasmic reticulum chaperone

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008112.2 RefSeqGene

    Range
    5009..256653
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001037633.2 → NP_001032722.1  nucleotide exchange factor SIL1 precursor

    See identical proteins and their annotated locations for NP_001032722.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AC008614, AC011378, AC011405, CA415266, CB125000, CD369479
    Consensus CDS
    CCDS4209.1
    UniProtKB/Swiss-Prot
    D3DQC2, Q8N2L3, Q9H173
    UniProtKB/TrEMBL
    A0A0S2Z6B4, D6REA1
    Related
    ENSP00000265195.5, ENST00000265195.9
    Conserved Domains (1) summary
    pfam08609
    Location:192 → 222
    Fes1; Nucleotide exchange factor Fes1

  2. NM_022464.5 → NP_071909.1  nucleotide exchange factor SIL1 precursor

    See identical proteins and their annotated locations for NP_071909.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the 5'UTR compared to variant 1. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AK074624, BC011568, CA415266, CD369479
    Consensus CDS
    CCDS4209.1
    UniProtKB/Swiss-Prot
    D3DQC2, Q8N2L3, Q9H173
    UniProtKB/TrEMBL
    A0A0S2Z6B4, D6REA1
    Related
    ENSP00000378294.2, ENST00000394817.7
    Conserved Domains (1) summary
    pfam08609
    Location:192 → 222
    Fes1; Nucleotide exchange factor Fes1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    138946724..139198368 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011543570.3 → XP_011541872.1  nucleotide exchange factor SIL1 isoform X1

    UniProtKB/TrEMBL
    D6REA1
    Conserved Domains (1) summary
    pfam08609
    Location:203 → 232
    Fes1; Nucleotide exchange factor Fes1

  2. XM_047417498.1 → XP_047273454.1  nucleotide exchange factor SIL1 isoform X2

    UniProtKB/Swiss-Prot
    D3DQC2, Q8N2L3, Q9H173
    UniProtKB/TrEMBL
    A0A0S2Z6B4

  3. XM_047417496.1 → XP_047273452.1  nucleotide exchange factor SIL1 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    139472860..139724442 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054353098.1 → XP_054209073.1  nucleotide exchange factor SIL1 isoform X1

  2. XM_054353100.1 → XP_054209075.1  nucleotide exchange factor SIL1 isoform X2

    UniProtKB/Swiss-Prot
    D3DQC2, Q8N2L3, Q9H173
    UniProtKB/TrEMBL
    A0A0S2Z6B4

  3. XM_054353099.1 → XP_054209074.1  nucleotide exchange factor SIL1 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9H173.1 GenPept UniProtKB/Swiss-Prot:Q9H173

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