Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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SEL1 Sel1-like repeats.

SMART accession number:	SM00671
Description:	These represent a subfamily of TPR (tetratricopeptide repeat) sequences.
Interpro abstract (IPR006597):	Sel1-like repeats are tetratricopeptide repeat sequences originally identified in a Caenorhabditis elegans receptor molecule which is a key negative regulator of the Notch pathway [(PUBMED:8722778)]. Mammalian homologues have since been identified although these mainly pancreatic proteins have yet to have a function assigned.
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 23408 SEL1 domains in 4662 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a SEL1 domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with SEL1 domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Cellular role (predicted cellular role)

• Cellular role: signalling
  Binding / catalysis: unknown

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Grant B, Greenwald I
  • The Caenorhabditis elegans sel-1 gene, a negative regulator of lin-12 andglp-1, encodes a predicted extracellular protein.
  • Genetics. 1996; 143: 237-47
  • Display abstract

  • The Caenorhabditis elegans lin-12 and glp-1 genes encode members of theLIN-12/NOTCH family of receptors. The sel-1 gene was identified as anextragenic suppressor of a lin-12 hypomorphic mutant. We show in thisreport that the sel-1 null phenotype is wild type, except for an apparentelevation in lin-12 and glp-1 activity in sensitized genetic backgrounds,and that this genetic interaction seems to be lin-12 and glp-1 specific.We also find that sel-1 encodes a predicted extracellular protein, with adomain sharing sequence similarity to predicted proteins from humans andyeast. SEL-1 may interact with the LIN-12 and GLP-1 receptors and/or theirrespective ligands to down-regulate signaling.

  • Hampton RY, Gardner RG, Rine J
  • Role of 26S proteasome and HRD genes in the degradation of3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmicreticulum membrane protein.
  • Mol Biol Cell. 1996; 7: 2029-44
  • Display abstract

  • 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R), a key enzyme of sterolsynthesis, is an integral membrane protein of the endoplasmic reticulum(ER). In both humans and yeast, HMG-R is degraded at or in the ER. Thedegradation of HMG-R is regulated as part of feedback control of themevalonate pathway. Neither the mechanism of degradation nor the nature ofthe signals that couple the degradation of HMG-R to the mevalonate pathwayis known. We have launched a genetic analysis of the degradation of HMG-Rin Saccharomyces cerevisiae using a selection for mutants that aredeficient in the degradation of Hmg2p, an HMG-R isozyme. The underlyinggenes are called HRD (pronounced "herd"), for HMG-CoA reductasedegradation. So far we have discovered mutants in three genes: HRD1, HRD2,and HRD3. The sequence of the HRD2 gene is homologous to the p97 activatorof the 26S proteasome. This p97 protein, also called TRAP-2, has beenproposed to be a component of the mature 26S proteasome. The hrd2-1 mutanthad numerous pleiotropic phenotypes expected for cells with a compromisedproteasome, and these phenotypes were complemented by the human TRAP-2/p97coding region. In contrast, HRD1 and HRD3 genes encoded previously unknownproteins predicted to be membrane bound. The Hrd3p protein was homologousto the Caenorhabditis elegans sel-1 protein, a negative regulator of atleast two different membrane proteins, and contained an HRD3 motif sharedwith several other proteins. Hrd1p had no full-length homologues, butcontained an H2 ring finger motif. These data suggested a model of ERprotein degradation in which the Hrd1p and Hrd3p proteins conspire todeliver HMG-R to the 26S proteasome. Moreover, our results lend in vivosupport to the proposed role of the p97/TRAP-2/Hrd2p protein as afunctionally important component of the 26S proteasome. Because the HRDgenes were required for the degradation of both regulated and unregulatedsubstrates of ER degradation, the HRD genes are the agents of HMG-Rdegradation but not the regulators of that degradation.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 23.68 map00312 beta-Lactam resistance 23.68 map00311 Penicillin and cephalosporin biosynthesis 23.68 map02020 Two-component system - General 2.63 map00251 Glutamate metabolism 2.63 map00010 Glycolysis / Gluconeogenesis 2.63 map00564 Glycerophospholipid metabolism 2.63 map00710 Carbon fixation 2.63 map00620 Pyruvate metabolism 2.63 map00592 alpha-Linolenic acid metabolism 2.63 map00240 Pyrimidine metabolism 2.63 map04930 Type II diabetes mellitus 2.63 map00530 Aminosugars metabolism 2.63 map04910 Insulin signaling pathway 2.63 map00230 Purine metabolism This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with SEL1 domain which could be assigned to a KEGG orthologous group, and not all proteins containing SEL1 domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of SEL1 domains in PDB

  PDB code	Main view	Title
  1klx		Helicobacter pylori cysteine rich protein b (hcpb)
  1na0		Design of stable alpha-helical arrays from an idealized tpr motif
  1na3		Design of stable alpha-helical arrays from an idealized tpr motif
  1ouv		Helicobacter cysteine rich protein c (hcpc)
  2avp		Crystal structure of an 8 repeat consensus tpr superhelix
  2fo7		Crystal structure of an 8 repeat consensus tpr superhelix (trigonal crystal form)
  2hyz		Crystal structure of an 8 repeat consensus tpr superhelix (orthorombic crystal form)
  3e4b		Crystal structure of algk from pseudomonas fluorescens wcs374r

• Links (links to other resources describing this domain)

• INTERPRO	IPR006597

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