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Aliases for SMCR8 Gene

Aliases for SMCR8 Gene

  • Smith-Magenis Syndrome Chromosome Region, Candidate 8 2 3 5
  • Smith-Magenis Syndrome Chromosomal Region Candidate Gene 8 Protein 4

External Ids for SMCR8 Gene

Previous GeneCards Identifiers for SMCR8 Gene

  • GC17P018463
  • GC17P019590
  • GC17P018161
  • GC17P018420
  • GC17P018421
  • GC17P018159
  • GC17P018218
  • GC17P017972
  • GC17P018317
  • GC17P018359
  • GC17P018409
  • GC17P018445
  • GC17P018453
  • GC17P018473

Summaries for SMCR8 Gene

GeneCards Summary for SMCR8 Gene

SMCR8 (Smith-Magenis Syndrome Chromosome Region, Candidate 8) is a Protein Coding gene. Diseases associated with SMCR8 include Smith-Magenis Syndrome and Dementia, Frontotemporal.

UniProtKB/Swiss-Prot for SMCR8 Gene

  • Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (PubMed:28195531).

Additional gene information for SMCR8 Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for SMCR8 Gene

Genomics for SMCR8 Gene

Regulatory Elements for SMCR8 Gene

Enhancers for SMCR8 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH17H018410 1.2 ENCODE dbSUPER 47.8 +96.0 95970 1.5 SIN3A GLI4 ZNF2 ZNF302 KLF7 SP3 YY2 REST TSHZ1 ZNF488 FOXO3B MAPK7 DRG2 SMCR8 ZNF286B ENSG00000264885 SMCR5 SHMT1 ENSG00000262202 NOS2P2
GH17H019254 0.9 dbSUPER 59.7 +939.7 939678 1.7 ZNF493 ZFP64 ZNF121 ZNF302 KLF7 ZNF202 SP3 ZC3H11A REST ZNF623 ENSG00000264885 FOXO3B MAPK7 FAM106A SMCR8 CCDC144B ZNF286B ENSG00000262202 ENSG00000273018 ENSG00000264932
GH17H017970 1.7 FANTOM5 ENCODE dbSUPER 30.5 -343.2 -343217 3.1 HDGF PKNOX1 FOXA2 ARID4B SIN3A DMAP1 ZBTB7B YY1 SLC30A9 ZNF143 SMCR8 FAM106A FOXO3B RAI1 DRG2 TOM1L2 FLII ZNF286B USP32P2 CCDC144B
GH17H018181 1.7 FANTOM5 ENCODE dbSUPER 29.9 -130.2 -130201 8 HDGF PKNOX1 ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 CBX5 ZNF143 SMCR8 MYO15A MIEF2 FAM106A NOS2P2 FOXO3B SHMT1 TBC1D3P4 YWHAEP2 ENSG00000262262
GH17H017913 1.9 FANTOM5 Ensembl ENCODE dbSUPER 23.1 -401.0 -401002 1.6 PKNOX1 ATF1 MLX ARID4B SIN3A FEZF1 BRCA1 ZNF2 TCF12 GLIS2 DRG2 RAI1 FOXO3B ENSG00000264885 SMCR8 LOC100419436 RPL13P12 ZNF286B FAM106A MPRIP-AS1
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around SMCR8 on UCSC Golden Path with GeneCards custom track

Genomic Locations for SMCR8 Gene

Genomic Locations for SMCR8 Gene
chr17:18,315,280-18,328,056
(GRCh38/hg38)
Size:
12,777 bases
Orientation:
Plus strand
chr17:18,218,594-18,231,370
(GRCh37/hg19)

Genomic View for SMCR8 Gene

Genes around SMCR8 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SMCR8 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SMCR8 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SMCR8 Gene

Proteins for SMCR8 Gene

  • Protein details for SMCR8 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TEV9-SMCR8_HUMAN
    Recommended name:
    Guanine nucleotide exchange protein SMCR8
    Protein Accession:
    Q8TEV9
    Secondary Accessions:
    • A5PKZ5
    • Q3ZCN0
    • Q6PJL3

    Protein attributes for SMCR8 Gene

    Size:
    937 amino acids
    Molecular mass:
    105022 Da
    Quaternary structure:
    • Interacts with C9orf72; the interaction is direct (PubMed:27559131, PubMed:27617292). Component of the C9orf72-SMCR8 complex, at least composed of C9orf72, SMCR8 and WDR41 (PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex associates with the ATG1/ULK1 kinase complex (PubMed:28195531).

    Alternative splice isoforms for SMCR8 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for SMCR8 Gene

Post-translational modifications for SMCR8 Gene

  • Phosphorylation by TBK1 is required to promote autophagosome maturation (PubMed:27103069). Phosphorylated by ULK1 (PubMed:27103069).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for SMCR8 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for SMCR8 Gene

Domains & Families for SMCR8 Gene

Gene Families for SMCR8 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for SMCR8 Gene

ProtoNet:

Suggested Antigen Peptide Sequences for SMCR8 Gene

Graphical View of Domain Structure for InterPro Entry

Q8TEV9

UniProtKB/Swiss-Prot:

SMCR8_HUMAN :
  • Belongs to the SMCR8 family.
Family:
  • Belongs to the SMCR8 family.
genes like me logo Genes that share domains with SMCR8: view

Function for SMCR8 Gene

Molecular function for SMCR8 Gene

UniProtKB/Swiss-Prot Function:
Component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy (PubMed:20562859, PubMed:27193190, PubMed:27103069, PubMed:27559131, PubMed:27617292, PubMed:28195531). In the complex, C9orf72 and SMCR8 probably constitute the catalytic subunits that promote the exchange of GDP to GTP, converting inactive GDP-bound RAB8A and RAB39B into their active GTP-bound form, thereby promoting autophagosome maturation (PubMed:20562859, PubMed:27103069, PubMed:27617292, PubMed:28195531). The C9orf72-SMCR8 complex also acts as a negative regulator of autophagy initiation by interacting with the ATG1/ULK1 kinase complex and inhibiting its protein kinase activity (PubMed:27617292, PubMed:28195531). Acts as a regulator of mTORC1 signaling by promoting phosphorylation of mTORC1 substrates (PubMed:27559131, PubMed:28195531). In addition to its activity in the cytoplasm within the C9orf72-SMCR8 complex, SMCR8 also localizes in the nucleus, where it associates with chromatin and negatively regulates expression of suppresses ULK1 and WIPI2 genes (PubMed:28195531).

Phenotypes From GWAS Catalog for SMCR8 Gene

Gene Ontology (GO) - Molecular Function for SMCR8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004860 protein kinase inhibitor activity IMP 28195531
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005515 protein binding IPI 27103069
GO:0017112 contributes_to Rab guanyl-nucleotide exchange factor activity IDA 27103069
GO:0019901 protein kinase binding IPI 27103069
genes like me logo Genes that share ontologies with SMCR8: view

Phenotypes for SMCR8 Gene

genes like me logo Genes that share phenotypes with SMCR8: view

Animal Models for SMCR8 Gene

MGI Knock Outs for SMCR8:

Animal Model Products

miRNA for SMCR8 Gene

miRTarBase miRNAs that target SMCR8

Clone Products

  • Addgene plasmids for SMCR8

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for SMCR8 Gene

Localization for SMCR8 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SMCR8 Gene

Cytoplasm. Nucleus. Note=Localizes mainly in the cytoplasm. {ECO:0000269 PubMed:28195531}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SMCR8 gene
Compartment Confidence
nucleus 5
lysosome 2
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for SMCR8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin IDA 28195531
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA 28195531
GO:0005737 cytoplasm IDA,IEA 27193190
GO:0032045 guanyl-nucleotide exchange factor complex IDA 27103069
genes like me logo Genes that share ontologies with SMCR8: view

Pathways & Interactions for SMCR8 Gene

SuperPathways for SMCR8 Gene

No Data Available

Gene Ontology (GO) - Biological Process for SMCR8 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006469 negative regulation of protein kinase activity IMP 28195531
GO:0006914 autophagy IEA --
GO:0010506 regulation of autophagy IMP,IEA 27103069
genes like me logo Genes that share ontologies with SMCR8: view

No data available for Pathways by source and SIGNOR curated interactions for SMCR8 Gene

Drugs & Compounds for SMCR8 Gene

No Compound Related Data Available

Transcripts for SMCR8 Gene

mRNA/cDNA for SMCR8 Gene

Clone Products

  • Addgene plasmids for SMCR8

Alternative Splicing Database (ASD) splice patterns (SP) for SMCR8 Gene

No ASD Table

Relevant External Links for SMCR8 Gene

GeneLoc Exon Structure for
SMCR8
ECgene alternative splicing isoforms for
SMCR8

Expression for SMCR8 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for SMCR8 Gene

Protein differential expression in normal tissues from HIPED for SMCR8 Gene

This gene is overexpressed in Monocytes (23.7), Ovary (16.8), Frontal cortex (10.6), and Testis (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for SMCR8 Gene



Protein tissue co-expression partners for SMCR8 Gene

NURSA nuclear receptor signaling pathways regulating expression of SMCR8 Gene:

SMCR8

SOURCE GeneReport for Unigene cluster for SMCR8 Gene:

Hs.592944

mRNA Expression by UniProt/SwissProt for SMCR8 Gene:

Q8TEV9-SMCR8_HUMAN
Tissue specificity: Expressed in all tissues tested.

Evidence on tissue expression from TISSUES for SMCR8 Gene

  • Eye(4.2)
  • Nervous system(3.4)
  • Intestine(2.8)
  • Lung(2.7)
genes like me logo Genes that share expression patterns with SMCR8: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for SMCR8 Gene

Orthologs for SMCR8 Gene

This gene was present in the common ancestor of chordates.

Orthologs for SMCR8 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia SMCR8 33 34
  • 99.72 (n)
dog
(Canis familiaris)
Mammalia SMCR8 33 34
  • 88.76 (n)
rat
(Rattus norvegicus)
Mammalia Smcr8 33
  • 86.1 (n)
mouse
(Mus musculus)
Mammalia Smcr8 33 16 34
  • 86.06 (n)
oppossum
(Monodelphis domestica)
Mammalia SMCR8 34
  • 82 (a)
OneToOne
cow
(Bos Taurus)
Mammalia SMCR8 33 34
  • 81.79 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia SMCR8 34
  • 76 (a)
OneToOne
chicken
(Gallus gallus)
Aves SMCR8 34 33
  • 71.9 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia SMCR8 34
  • 70 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia smcr8 33
  • 63.42 (n)
zebrafish
(Danio rerio)
Actinopterygii smcr8a 33 34
  • 60.21 (n)
smcr8b 34
  • 40 (a)
OneToMany
Species where no ortholog for SMCR8 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for SMCR8 Gene

ENSEMBL:
Gene Tree for SMCR8 (if available)
TreeFam:
Gene Tree for SMCR8 (if available)

Paralogs for SMCR8 Gene

No data available for Paralogs for SMCR8 Gene

Variants for SMCR8 Gene

Sequence variations from dbSNP and Humsavar for SMCR8 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
rs1000087819 -- 18,327,062(+) CTGGA(A/G)ATATG utr-variant-3-prime
rs1000110566 -- 18,322,248(+) CCTCA(C/T)GATGC intron-variant
rs1000176296 -- 18,315,742(+) ACACC(A/G)CATTC upstream-variant-2KB, utr-variant-5-prime
rs1000183037 -- 18,323,299(+) CCTGG(G/T)GAAGA utr-variant-3-prime
rs1000399078 -- 18,322,023(+) TTTTG(-/T)TTTTT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for SMCR8 Gene

Variant ID Type Subtype PubMed ID
nsv833387 CNV loss 17160897
nsv833386 CNV gain 17160897
nsv521075 CNV loss 19592680
nsv499114 OTHER inversion 21111241
nsv473957 CNV novel sequence insertion 20440878
nsv428333 CNV gain 18775914
nsv155 OTHER inversion 15895083
esv1004827 CNV deletion 20482838

Variation tolerance for SMCR8 Gene

Residual Variation Intolerance Score: 36.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.54; 85.99% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for SMCR8 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
SMCR8

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SMCR8 Gene

Disorders for SMCR8 Gene

MalaCards: The human disease database

(3) MalaCards diseases for SMCR8 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
smith-magenis syndrome
  • 17p11.2 microdeletion syndrome
dementia, frontotemporal
  • dementia, frontotemporal, with or without parkinsonism
amyotrophic lateral sclerosis 1
  • amyotrophic lateral sclerosis
- elite association - COSMIC cancer census association via MalaCards
Search SMCR8 in MalaCards View complete list of genes associated with diseases

Relevant External Links for SMCR8

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
SMCR8
genes like me logo Genes that share disorders with SMCR8: view

No data available for UniProtKB/Swiss-Prot and Genatlas for SMCR8 Gene

Publications for SMCR8 Gene

  1. Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death. (PMID: 27103069) Sellier C … Charlet-Berguerand N (The EMBO journal 2016) 2 3 4 60
  2. Discovery of Novel DENN Proteins: Implications for the Evolution of Eukaryotic Intracellular Membrane Structures and Human Disease. (PMID: 23248642) Zhang D … Aravind L (Frontiers in genetics 2012) 2 3 4 60
  3. Genes in a refined Smith-Magenis syndrome critical deletion interval on chromosome 17p11.2 and the syntenic region of the mouse. (PMID: 11997338) Bi W … Lupski JR (Genome research 2002) 2 3 4 60
  4. <strong></strong>Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator. (PMID: 28195531) Jung J … Behrends C (eLife 2017) 3 4 60
  5. A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in autophagy. (PMID: 27617292) Yang M … Chen JF (Science advances 2016) 3 4 60

Products for SMCR8 Gene

  • Addgene plasmids for SMCR8

Sources for SMCR8 Gene

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