SCS22/YBL091C-A Summary Help

Standard Name SCS22 1
Systematic Name YBL091C-A
Feature Type ORF, Verified
Description Protein involved in regulation of phospholipid metabolism; one of 6 proteins (Ist2p, Scs2p, Scs22p, Tcb1p, Tcb2p, Tcb3p) that connect ER to the plasma membrane (PM) and regulate PM phosphatidylinositol-4-phosphate (PI4P) levels by controlling access of Sac1p phosphatase to its substrate PI4P in the PM; similar to D. melanogaster inturned protein; SCS22 has a paralog, SCS2, that arose from the whole genome duplication (1, 2, 3 and see Summary Paragraph)
Name Description Suppressor of Choline Sensitivity 4
Chromosomal Location
ChrII:47180 to 46565 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All SCS22 GO evidence and references
  View Computational GO annotations for SCS22
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Resources
Large-scale survey
null
overexpression
Resources
22 total interaction(s) for 22 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 3
  • Biochemical Activity: 1
  • PCA: 2
  • Protein-RNA: 1
  • Two-hybrid: 4

Genetic Interactions
  • Negative Genetic: 11

Resources
Expression Summary
histogram
Resources
Length (a.a.) 175
Molecular Weight (Da) 19,678
Isoelectric Point (pI) 9.56
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrII:47180 to 46565 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 2004-01-07
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..34 47180..47147 2011-02-03 2004-01-07
Intron 35..122 47146..47059 2011-02-03 2004-01-07
CDS 123..616 47058..46565 2011-02-03 2004-01-07
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000007228
SUMMARY PARAGRAPH for SCS22

SCS22 encodes a VAP (VAMP/synaptobrevin-associated protein) family member that appears to play a minor role in the regulation of phospholipid biosynthesis (1). Scs22p has sequence similarity with Scs2p, a type II membrane protein (5, 6) that regulates intracellular lipid traffic and phospholipid biosynthesis (6). Strains deleted for SCS2 have a conditional inositol auxotrophy that can be suppressed by overexpression of the rate-limiting enzyme in inositol synthesis (INO1) (5), or by deletion of genes in the CDP-choline pathway (CKI1, PCT1, and CPT1) (7), while strains deleted for SCS22 alone do not exhibit an inositol auxotrophy (1). However, scs2 scs22 double mutants have a more severe phenotype than scs2 single mutants, suggesting a parallel function for SCS22 (1). Strains deleted for SCS2 also have a telomere silencing defect (8). However, strains deleted for SCS22 are not defective for silencing at the telomere, nor do they modify the silencing defect of an scs2 single mutant (8).

SCS22 has sequence similarity with three human VAP family members VAP-A (OMIM), VAP-B (OMIM) and VAP-C (OMIM) (a VAP-B splicing variant) (9) that are involved in recruiting FFAT (two phenylalanines (FF) in an Acidic Tract)-motif containing lipid-binding proteins to the ER similar to the SCS2 protein in yeast (10, 1, 6). Human VAP family members have also been implicated in both vesicular trafficking and organization of microtubule networks (references found within 11). The human VAP-A gene can partially complement the function of yeast VAPs by rescuing the inositol auxotrophy of an scs2 scs22 double mutant under less stringent conditions, and this rescue is dependent upon the integrity of the FFAT-binding region of VAP-A (1). Mutations in the human VAP-B gene cause atypical amyotrophic lateral sclerosis (ALS) type 8 (a neurodegenerative disease also known as Lou Gehrig's disease; OMIM), and late-onset spinal muscular atrophy (SMA) (OMIM) (12).

Last updated: 2007-06-01 Contact SGD

References cited on this page View Complete Literature Guide for SCS22
1) Loewen CJ and Levine TP  (2005) A highly conserved binding site in vesicle-associated membrane protein-associated protein (VAP) for the FFAT motif of lipid-binding proteins. J Biol Chem 280(14):14097-104
2) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
3) Manford AG, et al.  (2012) ER-to-Plasma Membrane Tethering Proteins Regulate Cell Signaling and ER Morphology. Dev Cell 23(6):1129-40
4) Hosaka K, et al.  (1994) Cloning and characterization of the SCS1 gene required for the expression of genes in yeast phospholipid synthesis. J Biochem (Tokyo) 115(1):131-6
5) Kagiwada S, et al.  (1998) The Saccharomyces cerevisiae SCS2 gene product, a homolog of a synaptobrevin-associated protein, is an integral membrane protein of the endoplasmic reticulum and is required for inositol metabolism. J Bacteriol 180(7):1700-8
6) Loewen CJ, et al.  (2003) A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP. EMBO J 22(9):2025-35
7) Kagiwada S and Zen R  (2003) Role of the yeast VAP homolog, Scs2p, in INO1 expression and phospholipid metabolism. J Biochem (Tokyo) 133(4):515-22
8) Craven RJ and Petes TD  (2001) The Saccharomyces cerevisiae suppressor of choline sensitivity (SCS2) gene is a multicopy Suppressor of mec1 telomeric silencing defects. Genetics 158(1):145-54
9) Nishimura Y, et al.  (1999) Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins. Biochem Biophys Res Commun 254(1):21-6
10) Wyles JP and Ridgway ND  (2004) VAMP-associated protein-A regulates partitioning of oxysterol-binding protein-related protein-9 between the endoplasmic reticulum and Golgi apparatus. Exp Cell Res 297(2):533-47
11) Kaiser SE, et al.  (2005) Structural basis of FFAT motif-mediated ER targeting. Structure 13(7):1035-45
12) Nishimura AL, et al.  (2004) A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 75(5):822-31