SEC12/YNR026C Single Page Format

This page provides an alternative format to the SGD Locus Summary Page. Note that additional information may be available on or linked from the standard format SGD Locus Summary page.

Contents
Names and Identifiers

GO Annotations

Pathways

Summary Paragraph

Mutant Phenotypes

Interactions

Homologs

Protein Info (physical properties, transcript info)

PDB Homologs (protein structure info)

Motifs

Genome-wide Expression
(and other large-scale analyses)

Locus History (misc. notes)

Sequence Retrieval and Analysis

Map and Displays

Localization

Community Annotation

Literature Guide

Sequence Coordinates

ChrXIV: 674692 to 673277
CDS: 674692 - 673277

Click on map for expanded view

SGD ORF map GBrowse
SGD Locus Page

Names and Identifiers [TOP] [NEXT]
Standard Name Systematic Name Alias Feature Type SGDID

SEC12 YNR026C SED2 ORF, Verified S000005309

Description
Guanine nucleotide exchange factor (GEF), activates Sar1p by catalyzing the exchange of GDP for GTP; required for the initiation of COPII vesicle formation in ER to Golgi transport; glycosylated integral membrane protein of the ER

GO Annotations [TOP] [NEXT]
Molecular Function
Annotation(s) Reference(s) Evidence Assigned By
GTPase activator activity GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.
     IEA : Inferred from Electronic Annotation with EBI:KW-0343
Assigned on 2008-02-14 UniProtKB
Sar guanyl-nucleotide exchange factor activity Barlowe C and Schekman R (1995) Expression, purification, and assay of Sec12p: a Sar1p-specific GDP dissociation stimulator. Methods Enzymol 257():98-106
     IDA : Inferred from Direct Assay
Assigned on 2010-01-05 SGD
Barlowe C and Schekman R (1993) SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER. Nature 365(6444):347-9
     IMP : Inferred from Mutant Phenotype
IDA : Inferred from Direct Assay
Assigned on 2010-01-05 SGD
Biological Process
Annotation(s) Reference(s) Evidence Assigned By
ER-nuclear signaling pathway Huttenhower C and Troyanskaya OG (2009) Prediction of Gene Ontology annotations by integrating high-throughput datasets
   RCA : Reviewed Computational Analysis
Assigned on 2009-08-06 bioPIXIE_MEFIT
protein transport GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.
     IEA : Inferred from Electronic Annotation with EBI:KW-0653
Assigned on 2007-05-23 UniProtKB
regulation of COPII vesicle coating Barlowe C and Schekman R (1993) SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER. Nature 365(6444):347-9
     IDA : Inferred from Direct Assay
Assigned on 2010-01-05 SGD
transport GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.
     IEA : Inferred from Electronic Annotation with EBI:KW-0813
Assigned on 2007-05-23 UniProtKB
vesicle-mediated transport GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.
     IEA : Inferred from Electronic Annotation with EBI:KW-0931
Assigned on 2008-02-14 UniProtKB
Cellular Component
Annotation(s) Reference(s) Evidence Assigned By
Golgi apparatus Nakano A, et al. (1988) A membrane glycoprotein, Sec12p, required for protein transport from the endoplasmic reticulum to the Golgi apparatus in yeast. J Cell Biol 107(3):851-63
     IDA : Inferred from Direct Assay
Assigned on 2010-01-05 SGD
GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.
     IEA : Inferred from Electronic Annotation with EBI:KW-0333
Assigned on 2009-06-29 UniProtKB
endoplasmic reticulum Sato M, et al. (1996) Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain. J Cell Biol 134(2):279-93
     IDA : Inferred from Direct Assay
Assigned on 2010-01-05 SGD
GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.
     IEA : Inferred from Electronic Annotation with EBI:KW-0256
Assigned on 2007-05-23 UniProtKB
integral to membrane GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.
     IEA : Inferred from Electronic Annotation with EBI:KW-0812
Assigned on 2007-05-23 UniProtKB
GOA curators and UniProt curators (2007) Gene Ontology annotation based on Swiss-Prot Subcellular Location vocabulary mapping.
     IEA : Inferred from Electronic Annotation with EBI:SL-9906
Assigned on 2009-10-01 UniProtKB
integral to membrane of membrane fraction Nakano A, et al. (1988) A membrane glycoprotein, Sec12p, required for protein transport from the endoplasmic reticulum to the Golgi apparatus in yeast. J Cell Biol 107(3):851-63
     IDA : Inferred from Direct Assay
Assigned on 2002-08-06 SGD
membrane GOA curators (2000) Gene Ontology annotation based on Swiss-Prot keyword mapping.
     IEA : Inferred from Electronic Annotation with EBI:KW-0472
Assigned on 2007-05-23 UniProtKB

Pathways [TOP] [NEXT]
No pathways available

Summary Paragraph [TOP] [NEXT]
SUMMARY PARAGRAPH for SEC12/YNR026C for SEC12
Transport of proteins from the endoplasmic reticulum (ER) to the Golgi is mediated by COPII vesicles (1). The COPII vesicle coat is minimally comprised of 5 subunits: the GTPase Sar1p, the Sec23p-Sec24p heterodimer, and the Sec13p-Sec31p complex (2, 3, 4, 5). COPII vesicle coats can also contain heterodimers of Sec23p complexed with either of the Sec24p homologs, Sfb2p or Sfb3p (6, 7, 8). In S. cerevisiae, COPII vesicle formation occurs throughout the ER (9). In most other eukaryotes, COPII vesicle-mediated protein export is localized to specialized regions termed transitional ER (tER) or ER exit sites (ERES) (3).
COPII vesicle formation requires the assembly of the COPII vesicle coat and cargo selection and is regulated by cycles of GTP hydrolysis. The GTP exchange factor (GEF) Sec12p, an ER membrane protein, activates Sar1p by exchanging GDP for GTP. Sar1p-GTP recruits the Sec23p-Sec24p heterodimer. Sec23p is a GTPase activating protein (GAP) for the Sar1p GTPase activity (10, 11, and reviewed in 3). Sec24p, Sfb2p, and Sfb3p, are involved in cargo selection (12, 8, 7). Sar1p, the Sec23p-Sec24p heterodimer, and cargo form the prebudding complex. Improper cargo selection results in GTP hydrolysis and diassembly of the prebudding complex (13). However, once the pre-budding complex is assembled, Sec13p and Sec31p polymerize to form the outer layer or scaffold of the COPII vesicle coat. The Sec13p-Sec31p complex further stimulates the GTPase activity of Sar1p (reviewed in 3).
Although Sar1p, Sec23p, Sec24p, Sec13p, and Sec31p are necessary and sufficient for vesicle formation, additional factors such as Sec16p and Sed4p are also involved in this process. Through interactions with other COPII proteins, Sec16p is thought to facilitate the assembly of the vesicle coat by stabilizing the pre-budding complex (14) while Sed4p may regulate the vesicle budding process by inhibiting the GAP activity of Sec23p (15).
Mutations in genes involved in COPII vesicle formation are also impaired in other processes such as ERAD (ER-associated degradation) and autophagy, suggesting that ER to the Golgi transport is a prerequisite for these processes to occur (16, 17, 18, 19).
Mutations in the human homolog of SEC23, Sec23A, cause the autosomal recessive disorder Cranio-lenticulo sutural dysplasia (CLSD), while mutation of Sar1B, one of the two human isoforms of S. cerevisiae Sar1p, cause defects in lipoprotein metabolism including the diseases that are known as the chylomicron retention diseases (CMRDs) (reviewed in 3).
Last Updated: 2010-01-07

Basic References [TOP]
BASIC INFORMATION REFERENCES forSEC12/YNR026C for SEC12
1) Bonifacino JS and Glick BS (2004) The mechanisms of vesicle budding and fusion. Cell 116(2):153-66

2) Lee MC and Miller EA (2007) Molecular mechanisms of COPII vesicle formation. Semin Cell Dev Biol 18(4):424-34

3) Hughes H and Stephens DJ (2008) Assembly, organization, and function of the COPII coat. Histochem Cell Biol 129(2):129-51

4) Barlowe C, et al. (1994) COPII: a membrane coat formed by Sec proteins that drive vesicle budding from the endoplasmic reticulum. Cell 77(6):895-907

5) Fath S, et al. (2007) Structure and organization of coat proteins in the COPII cage. Cell 129(7):1325-36

6) Peng R, et al. (2000) Evidence for overlapping and distinct functions in protein transport of coat protein Sec24p family members. J Biol Chem 275(15):11521-8

7) Miller E, et al. (2002) Cargo selection into COPII vesicles is driven by the Sec24p subunit. EMBO J 21(22):6105-13

8) Miller EA, et al. (2003) Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles. Cell 114(4):497-509

9) Rossanese OW, et al. (1999) Golgi structure correlates with transitional endoplasmic reticulum organization in Pichia pastoris and Saccharomyces cerevisiae. J Cell Biol 145(1):69-81

10) Barlowe C, et al. (1993) Purification and characterization of SAR1p, a small GTP-binding protein required for transport vesicle formation from the endoplasmic reticulum. J Biol Chem 268(2):873-9

11) Yoshihisa T, et al. (1993) Requirement for a GTPase-activating protein in vesicle budding from the endoplasmic reticulum. Science 259(5100):1466-8

12) Shimoni Y, et al. (2000) Lst1p and Sec24p cooperate in sorting of the plasma membrane ATPase into COPII vesicles in Saccharomyces cerevisiae. J Cell Biol 151(5):973-84

13) Sato K and Nakano A (2005) Dissection of COPII subunit-cargo assembly and disassembly kinetics during Sar1p-GTP hydrolysis. Nat Struct Mol Biol 12(2):167-74

14) Supek F, et al. (2002) Sec16p potentiates the action of COPII proteins to bud transport vesicles. J Cell Biol 158(6):1029-38

15) Saito-Nakano Y and Nakano A (2000) Sed4p functions as a positive regulator of Sar1p probably through inhibition of the GTPase activation by Sec23p. Genes Cells 5(12):1039-48

16) Taxis C, et al. (2002) ER-golgi traffic is a prerequisite for efficient ER degradation. Mol Biol Cell 13(6):1806-18

17) Hamasaki M, et al. (2003) The early secretory pathway contributes to autophagy in yeast. Cell Struct Funct 28(1):49-54

18) Fu L and Sztul E (2003) Traffic-independent function of the Sar1p/COPII machinery in proteasomal sorting of the cystic fibrosis transmembrane conductance regulator. J Cell Biol 160(2):157-63

19) Ishihara N, et al. (2001) Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol Biol Cell 12(11):3690-702

20) Barlowe C and Schekman R (1993) SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER. Nature 365(6444):347-9

21) d'Enfert C, et al. (1991) Sec12p-dependent membrane binding of the small GTP-binding protein Sar1p promotes formation of transport vesicles from the ER. J Cell Biol 114(4):663-70

22) Novick P and Schekman R (1979) Secretion and cell-surface growth are blocked in a temperature-sensitive mutant of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 76(4):1858-62

23) Novick P, et al. (1980) Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21(1):205-15

Mutant Phenotypes [TOP] [NEXT]
Phenotype page for SEC12/YNR026C

Interactions: genetic, physical, and other gene-gene links. [TOP] [NEXT]
Interaction page for SEC12/YNR026C

Homologs [TOP] [NEXT]

Comparison Resources

Physical Properties and Transcript Information: predicted from sequence [TOP] [NEXT]
Protein Sequence Calculations
from Predicted Full length Translation

N-term MKFVTAS

C-term FREIDDA

Length(aa) 471

MW(Da) 51,607

pI 6.75

Amino Acid Composition (full length)

GCG tools: PepPlot, Helical Wheel, PepStruct

Transcript Translation Calculations

Codon Bias 0.062

Codon Adaptation Index 0.137

Frequency of Optimal Codons 0.462

Hydropathicity of Protein -0.157

Aromaticity Score 0.081

10 20 30 40 50 | | | | | MKFVTASYNVGYPAYGAKFLNNDTLLVAGGGGEGNNGIPNKLTVLRVDPT KDTEKEQFHILSEFALEDNDDSPTAIDASKGIILVGCNENSTKITQGKGN KHLRKFKYDKVNDQLEFLTSVDFDASTNADDYTKLVYISREGTVAAIASS KVPAIMRIIDPSDLTEKFEIETRGEVKDLHFSTDGKVVAYITGSSLEVIS TVTGSCIARKTDFDKNWSLSKINFIADDTVLIAASLKKGKGIVLTKISIK SGNTSVLRSKQVTNRFKGITSMDVDMKGELAVLASNDNSIALVKLKDLSM SKIFKQAHSFAITEVTISPDSTYVASVSAANTIHIIKLPLNYANYTSMKQ KISKFFTNFILIVLLSYILQFSYKHNLHSMLFNYAKDNFLTKRDTISSPY VVDEDLHQTTLFGNHGTKTSVPSVDSIKVHGVHETSSVNGTEVLCTESNI INTGGAEFEITNATFREIDDA*

Protein Structures from PDB: proteins of known structure with sequence similarity to SEC12/YNR026C, based on Smith-Waterman analysis. [TOP] [NEXT]
No protein structure information available.

Genome-wide Expression and Other Large-Scale Analyses [TOP] [NEXT]

Functional Analysis
You can also search multiple datasets simultaneously using Expression Connection for expression studies or Function Junction for other large scale analyses.

Locus History (misc. notes) [TOP] [NEXT]
Nomenclature History
Standard Name Reference
SEC12 Novick P, et al. (1980) Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21(1):205-15

Standard Name	Reference
SEC12	*Novick P, et al.* (1980)** Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21(1):205-15

Sequence Retrieval [TOP] [NEXT]
Sequence Type Output Format

Genomic DNA GCG | FASTA | NoHeader

Genomic DNA with 1 kb up and downstream GCG | FASTA | NoHeader

DNA coding sequence
(without introns, without flanking regions) GCG | FASTA | NoHeader

Protein Translation of ORF GCG | FASTA | NoHeader

6-Frame Translation(with Restriction Map) GCG

Restriction Fragment Sizes GCG

Sequence Analysis Tools
Sequence from other databases

Sequence ID Source

YNR026C SGD Systematic Sequence

855760 NCBI: Gene ID

NP_014423.1 NCBI: RefSeq protein version ID

NP_014423.1 NCBI: RefSeq protein version ID

6324353 NCBI: NCBI protein GI

Sequence from other databases
Sequence ID	Source
YNR026C	SGD Systematic Sequence
855760	NCBI: Gene ID
NP_014423.1	NCBI: RefSeq protein version ID
NP_014423.1	NCBI: RefSeq protein version ID
6324353	NCBI: NCBI protein GI

Map and Displays [TOP] [NEXT]
Physical, Genetic Maps: Chromosomal Feature Map GBrowse Combined Physical and Genetic Map Genetic Distance vs. Physical Distance Ratios
Similarity Viewers: Synteny Viewer Genomic Stripe View SAGE Results Map

Localization [TOP] [NEXT]

Localization Resources

Community Annotation [TOP] [NEXT]
No community annotation available.

Literature Guide: papers categorized by topic. [TOP]
Topics Reference Other Genes Addressed
103 curated references; 0 references not yet curated
Mutants/Phenotypes
Strains/Constructs
Castillon GA, et al. (2009) Concentration of GPI-anchored proteins upon ER exit in yeast. Traffic 10(2):186-200
       |BST1 |CCW14 |CWP2 |EMP24 |ERV14 |GAP1 |GUP1 |HXT1 |HXT2 |MF(ALPHA)1 |MF(ALPHA)2 |MID2 |PER1 |SEC13 |MORE
Mutants/Phenotypes
Strains/Constructs
Mitsui K, et al. (2009) Saccharomyces cerevisiae Na+/H+ antiporter Nha1p associates with lipid rafts and requires sphingolipid for stable localization to the plasma membrane. J Biochem 145(6):709-20
       |END3 |LCB1 |NHA1 |PHO8 |PMA1 |SEC14 |SEC6 |VPH1 |VPS1
Mutants/Phenotypes
Murakami-Sekimata A, et al. (2009) O-Mannosylation is required for the solubilization of heterologously expressed human beta-amyloid precursor protein in Saccharomyces cerevisiae. Genes Cells 14(2):205-15
       |PMT1 |PMT2 |PMT4 |SEC18
Mutants/Phenotypes
Strains/Constructs
Perry RJ, et al. (2009) Endoplasmic Reticulum-Associated Secretory Proteins Sec20p, Sec39p, and Dsl1p Are Involved in Peroxisome Biogenesis. Eukaryot Cell 8(6):830-843
       |BOS1 |COP1 |DSL1 |PEX3 |POT1 |SEC1 |SEC11 |SEC13 |SEC14 |SEC17 |SEC18 |SEC20 |SEC21 |SEC26 |MORE
Mutants/Phenotypes
Strains/Constructs
Taxis C, et al. (2009) Efficient protein depletion by genetically controlled deprotection of a dormant N-degron. Mol Syst Biol 5:267
       |CDC14 |CDC48 |CDC5 |UBR1
Mutants/Phenotypes
Strains/Constructs
Teh EM, et al. (2009) Retention of Chs2p in the ER requires N-terminal CDK1-phosphorylation sites. Cell Cycle 8(18):2964-74
       |CDC15 |CHS2 |CLB2 |SEC7 |SED5 |SIC1
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Yakir-Tamang L and Gerst JE (2009) A phosphatidylinositol-transfer protein and phosphatidylinositol-4-phosphate 5-kinase control Cdc42 to regulate the actin cytoskeleton and secretory pathway in yeast. Mol Biol Cell 20(15):3583-97
       |CDC24 |CDC42 |MSS4 |MYO2 |SAC1 |SEC1 |SEC14 |SEC15 |SEC2 |SEC22 |SEC3 |SEC4 |SEC8 |SEC9 |MORE
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Zink S, et al. (2009) A link between ER tethering and COP-I vesicle uncoating. Dev Cell 17(3):403-16
       |ARF1 |ARF2 |COP1 |DSL1 |EMP47 |GCS1 |GLO3 |RER1 |RET2 |RET3 |SEC13 |SEC27 |SEC28 |SEC39 |MORE
Mutants/Phenotypes
Strains/Constructs
Breslow DK, et al. (2008) A comprehensive strategy enabling high-resolution functional analysis of the yeast genome. Nat Methods 5(8):711-8
       |AAR2 |ABD1 |ABF1 |ACC1 |ACP1 |ADE13 |AFG2 |ALA1 |ALG1 |ALG13 |ALG14 |ALG2 |ALG7 |ALR1 |MORE
Genetic Interactions
Higashio H, et al. (2008) Smy2p Participates in COPII Vesicle Formation Through the Interaction with Sec23p/Sec24p Subcomplex. Traffic 9(1):79-93
         |BET1 |COG2 |COG3 |RET1 |RET3 |SAR1 |SEC13 |SEC16 |SEC17 |SEC18 |SEC20 |SEC21 |SEC22 |SEC23 |MORE
Reviews
Hughes H and Stephens DJ (2008) Assembly, organization, and function of the COPII coat. Histochem Cell Biol 129(2):129-51
       |ARF1 |SAR1 |SEC13 |SEC16 |SEC23 |SEC24 |SMY2 |YIP1 |YOS1 |YPT1
Mutants/Phenotypes
Strains/Constructs
Okamoto M, et al. (2008) The cytoplasmic region of alpha-1,6-mannosyltransferase Mnn9p is crucial for retrograde transport from the Golgi apparatus to the endoplasmic reticulum in Saccharomyces cerevisiae. Eukaryot Cell 7(2):310-8
       |ERD1 |MNN9 |OCH1
Genetic Interactions
Strains/Constructs
Zabel R, et al. (2008) Yeast alpha-tubulin suppressor Ats1/Kti13 relates to the Elongator complex and interacts with Elongator partner protein Kti11. Mol Microbiol 69(1):175-87
       |ADE2 |ATS1 |CAN1 |ELP2 |ELP3 |ELP4 |ELP6 |HRR25 |IKI1 |IKI3 |KTI11 |KTI12 |NAP1 |SEC2 |MORE
Mutants/Phenotypes
Strains/Constructs
Faulhammer F, et al. (2007) Growth control of Golgi phosphoinositides by reciprocal localization of sac1 lipid phosphatase and pik1 4-kinase. Traffic 8(11):1554-67
             |DPM1 |FRQ1 |PIK1 |RER1 |SAC1 |SEC21 |SEC62
Reviews
Lee MC and Miller EA (2007) Molecular mechanisms of COPII vesicle formation. Semin Cell Dev Biol 18(4):424-34
       |SAR1 |SEC13 |SEC16 |SEC23 |SEC24
Reviews
Sato K and Nakano A (2007) Mechanisms of COPII vesicle formation and protein sorting. FEBS Lett 581(11):2076-82
       |SAR1 |SEC13 |SEC16 |SEC23 |SEC24
Fungal Related Genes/Proteins
Arakawa K, et al. (2006) Molecular cloning and characterization of a Pichia pastoris ortholog of the yeast Golgi GDP-mannose transporter gene. J Gen Appl Microbiol 52(3):137-45
       |GDA1 |OCH1 |SEC13
Strains/Constructs
Reggiori F and Klionsky DJ (2006) Atg9 sorting from mitochondria is impaired in early secretion and VFT-complex mutants in Saccharomyces cerevisiae. J Cell Sci 119(Pt 14):2903-11
       |ATG1 |ATG9 |SED5 |SPO7 |VPS4 |VPS51 |VPS52 |VPS53 |VPS54
Mutants/Phenotypes
Strains/Constructs
Zhang G, et al. (2006) Exit from mitosis triggers Chs2p transport from the endoplasmic reticulum to mother-daughter neck via the secretory pathway in budding yeast. J Cell Biol 174(2):207-20
       |CDC15 |CHS2 |CLB2 |SEC18 |SEC2 |SIC1
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
D'Alessio C, et al. (2005) Absence of nucleoside diphosphatase activities in the yeast secretory pathway does not abolish nucleotide sugar-dependent protein glycosylation. J Biol Chem 280(49):40417-27
       |ALG5 |GDA1 |UFE1 |YND1
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Davierwala AP, et al. (2005) The synthetic genetic interaction spectrum of essential genes. Nat Genet 37(10):1147-52
           |ABD1 |ACT1 |ALG13 |ALG14 |ALG7 |APC11 |ARL3 |ARP2 |ARP7 |ASK1 |AVO1 |BET3 |BET5 |BIM1 |MORE
Techniques and Reagents
Dixon C, et al. (2005) Alpha-synuclein targets the plasma membrane via the secretory pathway and induces toxicity in yeast. Genetics 170(1):47-59
       |HSP82 |PRE2 |SEC23 |SEC4 |SEC9 |YCK2
Function/Process
Mutants/Phenotypes
Protein Physical Properties
Protein Sequence Features
Protein-protein Interactions
Regulatory Role
Strains/Constructs
Substrates/Ligands/Cofactors
Futai E and Schekman R (2005) Purification and functional properties of yeast Sec12 GEF. Methods Enzymol 404():74-82
       |SAR1 |SEC23 |SEC24
Mutants/Phenotypes
Strains/Constructs
Inadome H, et al. (2005) Immunoisolaton of the yeast Golgi subcompartments and characterization of a novel membrane protein, Svp26, discovered in the Sed5-containing compartments. Mol Cell Biol 25(17):7696-710
       |AKR1 |ANP1 |ARF1 |ATG27 |DPM1 |EHT1 |EMP24 |EMP47 |ERP1 |ERP2 |ERV14 |ERV25 |ERV41 |ERV46 |MORE
Function/Process
Mutants/Phenotypes
Strains/Constructs
Ozeki-Miyawaki C, et al. (2005) Identification of functional domains of Mid1, a stretch-activated channel component, necessary for localization to the plasma membrane and Ca(2+) permeation. Exp Cell Res 311(1):84-95
       |MID1 |SEC6 |SEC7
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Routt SM, et al. (2005) Nonclassical PITPs activate PLD via the Stt4p PtdIns-4-kinase and modulate function of late stages of exocytosis in vegetative yeast. Traffic 6(12):1157-72
           |CSR1 |LSB6 |MSS4 |PDR16 |PDR17 |PIK1 |PSD1 |SAC1 |SEC1 |SEC10 |SEC13 |SEC14 |SEC15 |SEC16 |MORE
Function/Process
Sato K and Nakano A (2005) Dissection of COPII subunit-cargo assembly and disassembly kinetics during Sar1p-GTP hydrolysis. Nat Struct Mol Biol 12(2):167-74
       |SAR1 |SEC23 |SEC24
Reviews
Bonifacino JS and Glick BS (2004) The mechanisms of vesicle budding and fusion. Cell 116(2):153-66
       |BET1 |EMP24 |EMP46 |EMP47 |ERV25 |ERV41 |GAP1 |SAR1 |SEC13 |SEC16 |SEC17 |SEC18 |SEC23 |SEC24 |MORE
Cellular Location
Function/Process
Mutants/Phenotypes
Strains/Constructs
Reggiori F, et al. (2004) Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae. Mol Biol Cell 15(5):2189-204
       |ATG1 |ATG14 |ATG8 |LAP4 |SEC7 |STP22 |VPS27 |VPS28 |VPS34 |VPS4
Fungal Related Genes/Proteins
Soderholm J, et al. (2004) The transitional ER localization mechanism of Pichia pastoris Sec12. Dev Cell 6(5):649-59

Reviews
Duden R (2003) ER-to-Golgi transport: COP I and COP II function (Review). Mol Membr Biol 20(3):197-207
       |BET1 |BOS1 |SAR1 |SEC13 |SEC16 |SEC22 |SEC23 |SEC24 |SEC31
Function/Process
Mutants/Phenotypes
Strains/Constructs
Fu L and Sztul E (2003) Traffic-independent function of the Sar1p/COPII machinery in proteasomal sorting of the cystic fibrosis transmembrane conductance regulator. J Cell Biol 160(2):157-63
       |KAR2 |SAR1 |SEC13 |SEC23
Function/Process
Mutants/Phenotypes
Strains/Constructs
Hamasaki M, et al. (2003) The early secretory pathway contributes to autophagy in yeast. Cell Struct Funct 28(1):49-54
       |ATG8 |SEC13 |SEC24 |SEC31 |SFB2
Fungal Related Genes/Proteins
Nakamura-Kubo M, et al. (2003) The fission yeast spo14+ gene encoding a functional homologue of budding yeast Sec12 is required for the development of forespore membranes. Mol Biol Cell 14(3):1109-24
       |RER1 |SAR1
Reviews
Aridor M and Traub LM (2002) Cargo selection in vesicular transport: the making and breaking of a coat. Traffic 3(8):537-46
           |SAR1 |SEC13 |SEC16 |SEC23 |SEC24
Non-Fungal Related Genes/Proteins
Protein Sequence Features
Protein/Nucleic Acid Structure
Chardin P and Callebaut I (2002) The yeast Sar exchange factor Sec12, and its higher organism orthologs, fold as beta-propellers. FEBS Lett 525(1-3):171-3
             |SAR1
Function/Process
Mutants/Phenotypes
Fatal N, et al. (2002) Selective protein exit from yeast endoplasmic reticulum in absence of functional COPII coat component Sec13p. Mol Biol Cell 13(12):4130-40
       |HSP150 |SEC13 |SEC23 |SEC31
Function/Process
Mutants/Phenotypes
Strains/Constructs
Hanson PK, et al. (2002) NBD-labeled phosphatidylcholine enters the yeast vacuole via the pre-vacuolar compartment. J Cell Sci 115(Pt 13):2725-33
       |SLA2 |VPS28 |VPS4 |VPS8
Function/Process
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Sato M, et al. (2002) Evidence for the intimate relationship between vesicle budding from the ER and the unfolded protein response. Biochem Biophys Res Commun 296(3):560-7
         |HAC1 |IRE1 |SAR1
Function/Process
Mutants/Phenotypes
Strains/Constructs
Taxis C, et al. (2002) ER-golgi traffic is a prerequisite for efficient ER degradation. Mol Biol Cell 13(6):1806-18
       |DER1 |HRD1 |HRD3 |KAR2 |SEC18 |SEC23 |SED5 |UFE1
Function/Process
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Caldwell SR, et al. (2001) Degradation of endoplasmic reticulum (ER) quality control substrates requires transport between the ER and Golgi. J Biol Chem 276(26):23296-303
       |ERV29 |SEC18
Mutants/Phenotypes
Protein/Nucleic Acid Structure
Strains/Constructs
Techniques and Reagents
Dumon-Seignovert L, et al. (2001) Purification, crystallization and preliminary X-ray diffraction analysis of the yeast Sec12Deltap protein, a guanine nucleotide-exchange factor involved in vesicle transport. Acta Crystallogr D Biol Crystallogr 57(Pt 6):893-5

Function/Process
Mutants/Phenotypes
Strains/Constructs
Funato K and Riezman H (2001) Vesicular and nonvesicular transport of ceramide from ER to the Golgi apparatus in yeast. J Cell Biol 155(6):949-59
       |SEC16 |SEC17 |SEC18 |SEC23
Reviews
Gorelick FS and Shugrue C (2001) Exiting the endoplasmic reticulum. Mol Cell Endocrinol 177(1-2):13-8
       |SAR1 |SEC13 |SEC16 |SEC23 |SEC24 |SEC31
Function/Process
Mutants/Phenotypes
Strains/Constructs
Grant AM, et al. (2001) NBD-labeled phosphatidylcholine and phosphatidylethanolamine are internalized by transbilayer transport across the yeast plasma membrane. Traffic 2(1):37-50
       |SEC1 |SEC11 |SEC14 |SEC18 |SEC21 |SEC22 |SEC6 |SLA2
Function/Process
Mutants/Phenotypes
Strains/Constructs
Ishihara N, et al. (2001) Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol Biol Cell 12(11):3690-702
       |SEC13 |SEC16 |SEC18 |SEC23 |SEC24 |SEC31 |VTI1
Protein-protein Interactions
Massaad MJ and Herscovics A (2001) Interaction of the endoplasmic reticulum alpha 1,2-mannosidase Mns1p with Rer1p using the split-ubiquitin system. J Cell Sci 114(Pt 24):4629-35
       |ALG5 |MNS1 |OST1 |RER1
Protein-protein Interactions
Sato K, et al. (2001) Rer1p, a retrieval receptor for endoplasmic reticulum membrane proteins, is dynamically localized to the Golgi apparatus by coatomer. J Cell Biol 152(5):935-44
       |RER1
Cellular Location
Suzuki C (2001) Immunochemical and mutational analyses of P-type ATPase Spf1p involved in the yeast secretory pathway. Biosci Biotechnol Biochem 65(11):2405-11
     |KAR2 |OCH1 |SPF1
Non-Fungal Related Genes/Proteins
Weissman JT, et al. (2001) The mammalian guanine nucleotide exchange factor mSec12 is essential for activation of the Sar1 GTPase directing endoplasmic reticulum export. Traffic 2(7):465-75

Function/Process
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Finger FP and Novick P (2000) Synthetic interactions of the post-Golgi sec mutations of Saccharomyces cerevisiae. Genetics 156(3):943-51
       |ACT1 |CDC12 |CDC24 |CDC28 |CDC42 |DSS4 |GDI1 |MYO2 |SEC1 |SEC10 |SEC13 |SEC14 |SEC15 |SEC16 |MORE
Reviews
Kirchhausen T (2000) Three ways to make a vesicle. Nat Rev Mol Cell Biol 1(3):187-98
     |APL1 |APL2 |APL3 |APL4 |APM1 |APM4 |APS1 |APS2 |ARF1 |ARF2 |ARF3 |CHC1 |CLC1 |COP1 |MORE
Function/Process
Fungal Related Genes/Proteins
Protein Sequence Features
Payne WE, et al. (2000) Isolation of Pichia pastoris genes involved in ER-to-Golgi transport. Yeast 16(11):979-93
           |SAR1 |SEC13 |SEC17 |SEC18 |SED4
Cellular Location
Protein Sequence Features
Strains/Constructs
Reggiori F, et al. (2000) Polar transmembrane domains target proteins to the interior of the yeast vacuole. Mol Biol Cell 11(11):3737-49
         |CPS1 |NYV1 |PEP12 |UFE1 |VAM3
Function/Process
Genetic Interactions
Mutants/Phenotypes
Other Features
Strains/Constructs
Saito-Nakano Y and Nakano A (2000) Sed4p functions as a positive regulator of Sar1p probably through inhibition of the GTPase activation by Sec23p. Genes Cells 5(12):1039-48
       |SAR1 |SEC16 |SEC23 |SED4
Function/Process
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Gilstring CF, et al. (1999) Shr3p mediates specific COPII coatomer-cargo interactions required for the packaging of amino acid permeases into ER-derived transport vesicles. Mol Biol Cell 10(11):3549-65
       |GAL2 |GAP1 |PMA1 |SAR1 |SEC13 |SEC23 |SEC24 |SEC31 |SEC61 |SHR3
Function/Process
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Murakami A, et al. (1999) The inactive form of a yeast casein kinase I suppresses the secretory defect of the sec12 mutant. Implication of negative regulation by the Hrr25 kinase in the vesicle budding from the endoplasmic reticulum. J Biol Chem 274(6):3804-10
       |DIG1 |DIG2 |HRR25 |SAR1
Cellular Location
Function/Process
Rossanese OW, et al. (1999) Golgi structure correlates with transitional endoplasmic reticulum organization in Pichia pastoris and Saccharomyces cerevisiae. J Cell Biol 145(1):69-81
       |OCH1
Function/Process
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Saito Y, et al. (1999) Identification of SEC12, SED4, truncated SEC16, and EKS1/HRD3 as multicopy suppressors of ts mutants of Sar1 GTPase. J Biochem 125(1):130-7
       |HMG2 |HRD3 |KAR2 |SAR1 |SEC16 |SED4
Cellular Location
Protein Sequence Features
Protein-protein Interactions
Sato K, et al. (1999) The Arabidopsis thaliana RER1 gene family: its potential role in the endoplasmic reticulum localization of membrane proteins. Plant Mol Biol 41(6):815-24
     |RER1 |SEC63 |SEC66
Cellular Location
Strains/Constructs
Sato M, et al. (1999) The yeast RER2 gene, identified by endoplasmic reticulum protein localization mutations, encodes cis-prenyltransferase, a key enzyme in dolichol synthesis. Mol Cell Biol 19(1):471-83
       |RER2 |SEC59 |SRT1
Mutants/Phenotypes
Graham LA, et al. (1998) Assembly of the yeast vacuolar H+-ATPase occurs in the endoplasmic reticulum and requires a Vma12p/Vma22p assembly complex. J Cell Biol 142(1):39-49
       |VMA21 |VMA22 |VPH1 |VPH2
Cellular Location
Function/Process
Strains/Constructs
Matsuoka K, et al. (1998) Coat assembly directs v-SNARE concentration into synthetic COPII vesicles. Mol Cell 2(5):703-8
       |BOS1 |SEC22 |UFE1
Reviews
Sato K, et al. (1998) [The mechanisms of endoplasmic reticulum protein localization by vesicle recycling] Seikagaku 70(12):1387-400
     |RER1
Function/Process
Mutants/Phenotypes
Strains/Constructs
Wooding S and Pelham HR (1998) The dynamics of golgi protein traffic visualized in living yeast cells. Mol Biol Cell 9(9):2667-80
       |ANP1 |MNN1 |SEC14 |SEC18 |SED5 |SFT1 |SFT2
Cellular Location
Genetic Interactions
Strains/Constructs
Boehm J, et al. (1997) Sec12p requires Rer1p for sorting to coatomer (COPI)-coated vesicles and retrieval to the ER. J Cell Sci 110 ( Pt 8)():991-1003
       |COP1 |RER1
Mutants/Phenotypes
Protein Processing/Modification/Regulation
Protein Sequence Features
Protein-protein Interactions
Regulation of
Strains/Constructs
Campbell JL and Schekman R (1997) Selective packaging of cargo molecules into endoplasmic reticulum-derived COPII vesicles. Proc Natl Acad Sci U S A 94(3):837-42
         |EMP24 |SAR1 |SEC13 |SEC16 |SEC22 |SEC23 |SEC24 |SEC31
Genetic Interactions
Fullekrug J, et al. (1997) Human Rer1 is localized to the Golgi apparatus and complements the deletion of the homologous Rer1 protein of Saccharomyces cerevisiae. Eur J Cell Biol 74(1):31-40
     |RER1 |SAR1
Genetic Interactions
Kim WY, et al. (1997) The presence of a Sar1 gene family in Brassica campestris that suppresses a yeast vesicular transport mutation Sec12-1. Plant Mol Biol 33(6):1025-35
     |SAR1
Cellular Location
Sato K, et al. (1997) Rer1p as common machinery for the endoplasmic reticulum localization of membrane proteins. Proc Natl Acad Sci U S A 94(18):9693-8
       |COP1 |RER1 |SEC63 |SEC66
Cellular Location
Tang BL, et al. (1997) Endoplasmic reticulum retention mediated by the transmembrane domain of type II membrane proteins Sec12p and glucosidase 1. Eur J Cell Biol 73(2):98-104

Reviews
Urbe S, et al. (1997) Formation of secretory vesicles in the biosynthetic pathway. Biochim Biophys Acta 1358(1):6-22

Fungal Related Genes/Proteins
Non-Fungal Related Genes/Proteins
Veldhuisen G, et al. (1997) Isolation and analysis of functional homologues of the secretion-related SAR1 gene of Saccharomyces cerevisiae from Aspergillus niger and Trichoderma reesei. Mol Gen Genet 256(4):446-55
     |SAR1
Mutants/Phenotypes
McCracken AA and Brodsky JL (1996) Assembly of ER-associated protein degradation in vitro: dependence on cytosol, calnexin, and ATP. J Cell Biol 132(3):291-8

Genetic Interactions
Nakano A (1996) Identification and characterization of extragenic suppressors of the yeast sec12 ts mutation. J Biochem 120(3):642-6

Cellular Location
Sato M, et al. (1996) Endoplasmic reticulum localization of Sec12p is achieved by two mechanisms: Rer1p-dependent retrieval that requires the transmembrane domain and Rer1p-independent retention that involves the cytoplasmic domain. J Cell Biol 134(2):279-93
     |RER1
Techniques and Reagents
Barlowe C and Schekman R (1995) Expression, purification, and assay of Sec12p: a Sar1p-specific GDP dissociation stimulator. Methods Enzymol 257():98-106
     |SAR1
Fungal Related Genes/Proteins
Genetic Interactions
Gimeno RE, et al. (1995) SED4 encodes a yeast endoplasmic reticulum protein that binds Sec16p and participates in vesicle formation. J Cell Biol 131(2):325-38
     |SAR1 |SEC16 |SED4
Cellular Location
Sato K, et al. (1995) Membrane protein retrieval from the Golgi apparatus to the endoplasmic reticulum (ER): characterization of the RER1 gene product as a component involved in ER localization of Sec12p. Mol Biol Cell 6(11):1459-77
     |OCH1 |RER1 |YPT1
Mutants/Phenotypes
Sipos G, et al. (1995) Biosynthesis of the side chain of yeast glycosylphosphatidylinositol anchors is operated by novel mannosyltransferases located in the endoplasmic reticulum and the Golgi apparatus. J Biol Chem 270(34):19709-15
       |ANP1 |KRE2 |KTR1 |KTR2 |KTR3 |KTR4 |MNN1 |MNN2 |MNN5 |MNN9 |SEC18 |VAN1 |YUR1
Cellular Location
Strains/Constructs
Boehm J, et al. (1994) Kex2-dependent invertase secretion as a tool to study the targeting of transmembrane proteins which are involved in ER-->Golgi transport in yeast. EMBO J 13(16):3696-710
     |BET1 |KEX2 |RER1 |SEC22
Genetic Interactions
Letourneur F, et al. (1994) Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulum. Cell 79(7):1199-207
       |COP1 |GDI1 |SEC13 |SEC16 |SEC17 |SEC21 |SEC22 |SEC23 |SEC27 |STE2
Genetic Interactions
Techniques and Reagents
Nishikawa S, et al. (1994) Inhibition of endoplasmic reticulum (ER)-to-Golgi transport induces relocalization of binding protein (BiP) within the ER to form the BiP bodies. Mol Biol Cell 5(10):1129-43
     |KAR2 |SEC17 |SED4
Genetic Interactions
Techniques and Reagents
Oka T and Nakano A (1994) Inhibition of GTP hydrolysis by Sar1p causes accumulation of vesicles that are a functional intermediate of the ER-to-Golgi transport in yeast. J Cell Biol 124(4):425-34
     |SAR1 |SEC23
Function/Process
Regulatory Role
Substrates/Ligands/Cofactors
Barlowe C and Schekman R (1993) SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER. Nature 365(6444):347-9
     |SAR1 |SEC23
Strains/Constructs
Techniques and Reagents
Barlowe C, et al. (1993) Purification and characterization of SAR1p, a small GTP-binding protein required for transport vesicle formation from the endoplasmic reticulum. J Biol Chem 268(2):873-9
     |SAR1
Mutants/Phenotypes
Strains/Constructs
Techniques and Reagents
Kean LS, et al. (1993) Retrograde lipid traffic in yeast: identification of two distinct pathways for internalization of fluorescent-labeled phosphatidylcholine from the plasma membrane. J Cell Biol 123(6 Pt 1):1403-19
     |CHC1 |SEC1 |SEC11 |SEC14 |SEC17 |SEC18 |SEC2 |SEC21 |SEC4 |SEC6 |SEC63 |SEC65 |SEC7
Cellular Location
Genetic Interactions
Strains/Constructs
Nishikawa S and Nakano A (1993) Identification of a gene required for membrane protein retention in the early secretory pathway. Proc Natl Acad Sci U S A 90(17):8179-83
       |KAR2 |RER1 |RER2
Genetic Interactions
Hardwick KG, et al. (1992) Genes that allow yeast cells to grow in the absence of the HDEL receptor. EMBO J 11(11):4187-95
     |DPM1 |ERD2 |KAR2 |SED1 |SED4
Reviews
Pryer NK, et al. (1992) Vesicle-mediated protein sorting. Annu Rev Biochem 61:471-516
     |ARF1 |ARF2 |BET1 |BET2 |BOS1 |CHC1 |CLC1 |ERD1 |ERD2 |SAR1 |SEC1 |SEC13 |SEC14 |SEC15 |MORE
Fungal Related Genes/Proteins
Non-Fungal Related Genes/Proteins
d'Enfert C, et al. (1992) Fission yeast and a plant have functional homologues of the Sar1 and Sec12 proteins involved in ER to Golgi traffic in budding yeast. EMBO J 11(11):4205-11
     |SAR1
Techniques and Reagents
Oka T, et al. (1991) Reconstitution of GTP-binding Sar1 protein function in ER to Golgi transport. J Cell Biol 114(4):671-9
     |SAR1
Function/Process
Mutants/Phenotypes
Puoti A, et al. (1991) Biosynthesis of mannosylinositolphosphoceramide in Saccharomyces cerevisiae is dependent on genes controlling the flow of secretory vesicles from the endoplasmic reticulum to the Golgi. J Cell Biol 113(3):515-25
       |SEC13 |SEC14 |SEC16 |SEC17 |SEC18 |SEC20 |SEC21 |SEC22 |SEC23 |SEC6 |SEC7
Function/Process
Rexach MF and Schekman RW (1991) Distinct biochemical requirements for the budding, targeting, and fusion of ER-derived transport vesicles. J Cell Biol 114(2):219-29
     |SEC18 |SEC23 |YPT1
Function/Process
Protein-protein Interactions
Substrates/Ligands/Cofactors
d'Enfert C, et al. (1991) Sec12p-dependent membrane binding of the small GTP-binding protein Sar1p promotes formation of transport vesicles from the ER. J Cell Biol 114(4):663-70
     |SAR1
Function/Process
Mutants/Phenotypes
Protein Sequence Features
Strains/Constructs
d'Enfert C, et al. (1991) Structural and functional dissection of a membrane glycoprotein required for vesicle budding from the endoplasmic reticulum. Mol Cell Biol 11(11):5727-34
     |SAR1
Genetic Interactions
Mutants/Phenotypes
Kaiser CA and Schekman R (1990) Distinct sets of SEC genes govern transport vesicle formation and fusion early in the secretory pathway. Cell 61(4):723-33
       |SEC13 |SEC16 |SEC17 |SEC18 |SEC22 |SEC23
Reviews
Newman AP and Ferro-Novick S (1990) Defining components required for transport from the ER to the Golgi complex in yeast. Bioessays 12(10):485-91
     |ARF1 |ARF2 |BET1 |BET2 |BOS1 |SAR1 |SEC13 |SEC16 |SEC17 |SEC18 |SEC20 |SEC21 |SEC22 |SEC23 |MORE
Genetic Interactions
Nakano A and Muramatsu M (1989) A novel GTP-binding protein, Sar1p, is involved in transport from the endoplasmic reticulum to the Golgi apparatus. J Cell Biol 109(6 Pt 1):2677-91
     |SAR1
Cellular Location
Mutants/Phenotypes
Protein Processing/Modification/Regulation
Protein Sequence Features
Techniques and Reagents
Nakano A, et al. (1988) A membrane glycoprotein, Sec12p, required for protein transport from the endoplasmic reticulum to the Golgi apparatus in yeast. J Cell Biol 107(3):851-63

Function/Process
Mutants/Phenotypes
Strains/Constructs
Ramirez RM, et al. (1983) Plasma membrane expansion terminates in Saccharomyces cerevisiae secretion-defective mutants while phospholipid synthesis continues. J Bacteriol 154(3):1276-83
     |GDI1 |SEC1 |SEC10 |SEC11 |SEC13 |SEC14 |SEC15 |SEC16 |SEC17 |SEC18 |SEC2 |SEC20 |SEC21 |SEC22 |MORE
Function/Process
Mutants/Phenotypes
Strains/Constructs
Novick P, et al. (1981) Order of events in the yeast secretory pathway. Cell 25(2):461-9
       |GDI1 |SEC1 |SEC14 |SEC15 |SEC16 |SEC18 |SEC2 |SEC20 |SEC21 |SEC22 |SEC23 |SEC3 |SEC4 |SEC5 |MORE
Function/Process
Genetic Interactions
Mutants/Phenotypes
Strains/Constructs
Novick P, et al. (1980) Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21(1):205-15
       |GDI1 |SEC1 |SEC10 |SEC11 |SEC13 |SEC14 |SEC15 |SEC16 |SEC17 |SEC18 |SEC2 |SEC20 |SEC21 |SEC22 |MORE

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SGD^tm pages Database Copyright © 1997-2010 The Board of Trustees of Leland Stanford Junior University. Permission to use the information contained in this database was given by the researchers/institutes who contributed or published the information. Users of the database are solely responsible for compliance with any copyright restrictions, including those applying to the author abstracts. Documents from this server are provided "AS-IS" without any warranty, expressed or implied. The SGD project at Stanford University is supported by a Genome Research Resource Grant from the US National Human Genome Research Institute, part of the US National Institutes of Health.