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

    Gene ID: 64374, updated on 27-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (138946724..139198368, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (139472860..139724442, complement)
    RS_2024_09 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. 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
    2. SIL1 mutations and clinical spectrum in patients with Marinesco-Sjogren syndrome. Krieger M, et al. Brain, 2013 Dec. PMID 24176978
    3. Marinesco-Sjögren syndrome due to SIL1 mutations with a comment on the clinical phenotype. Horvers M, et al. Eur J Paediatr Neurol, 2013 Mar. PMID 23062754
    4. C-terminal mutations destabilize SIL1/BAP and can cause Marinesco-Sjögren syndrome. Howes J, et al. J Biol Chem, 2012 Mar 9. PMID 22219183, Free PMC Article
    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 (76) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Exome sequencing revealed variants in SGCA and SIL1 genes underlying limb girdle muscular dystrophy and Marinesco-Sjogren syndrome patients.
      Title: Exome sequencing revealed variants in SGCA and SIL1 genes underlying limb girdle muscular dystrophy and Marinesco-Sjögren syndrome patients.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (26)

    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
    		Compare labs

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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_2024_08

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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