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Q9U969 (SWS_DROME) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neuropathy target esterase sws
Alternative name(s):
Swiss cheese
Short name=DSWS
EC=3.1.1.5
Gene names
Name:sws
ORF Names:CG2212
OrganismDrosophila melanogaster (Fruit fly) [Reference proteome]
Taxonomic identifier7227 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora

Protein attributes

Sequence length1425 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Phospholipase B that deacylates intracellular phosphatidylcholine (PtdCho), generating glycerophosphocholine (GroPtdCho). This deacylation occurs at both sn-2 and sn-1 positions of PtdCho. Its specific chemical modification by certain organophosphorus (OP) compounds leads to distal axonopathy. Plays a role in the signaling mechanism between neurons and glia that regulates glia wrapping during development of the adult brain. Essential for membrane lipid homeostasis and cell survival in both neurons and glia of the adult brain. Ref.1 Ref.6 Ref.7

Catalytic activity

2-lysophosphatidylcholine + H2O = glycerophosphocholine + a carboxylate. Ref.6

Subunit structure

Interacts with Pka-C3; interaction inhibits the catalytic function of Pka-C3 and the esterase activity of sws. Ref.7

Subcellular location

Endoplasmic reticulum membrane; Single-pass type I membrane protein. Note: Sws tethers Pka-C3 to the membrane. Ref.6 Ref.7

Tissue specificity

Isoform A and isoform B are expressed in the entire brain cortex; cortical cell bodies of adult brain. Sws and Pka-C3 are colocalized in all neurons. Ref.1 Ref.6 Ref.7

Developmental stage

Isoform A is expressed in all developmental stages with highest levels in young embryos and adults. Isoform B is detected only in adult head. Ref.1

Disruption phenotype

Progressive degeneration of the adult nervous system, associated with apoptotic cell death, glial hyperwrapping, and neuronal apoptosis. Also, vacuolization in the neuropil. Ref.7

Sequence similarities

Belongs to the NTE family.

Contains 3 cyclic nucleotide-binding domains.

Contains 1 patatin domain.

Sequence caution

The sequence AAL28979.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: Q9U969-1)

Also known as: Long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform B (identifier: Q9U969-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1084: Missing.
     1087-1098: LSGYMPPLCDPK → IAGVFPPFCDYR
     1107-1112: GYVNNL → CYTNNV
Isoform C (identifier: Q9U969-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1087-1098: LSGYMPPLCDPK → IAGVFPPFCDYR
     1107-1112: GYVNNL → CYTNNV
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14251425Neuropathy target esterase sws
PRO_0000172527

Regions

Topological domain1 – 3434Lumenal Potential
Transmembrane35 – 5521Helical; Potential
Topological domain56 – 14251370Cytoplasmic Potential
Domain952 – 1118167Patatin
Nucleotide binding174 – 301128cNMP 1
Nucleotide binding482 – 609128cNMP 2
Nucleotide binding598 – 727130cNMP 3

Sites

Active site9851

Amino acid modifications

Modified residue4441Phosphoserine Ref.8
Modified residue4531Phosphoserine Ref.8
Modified residue11601Phosphoserine Ref.8

Natural variations

Alternative sequence1 – 10841084Missing in isoform B.
VSP_038398
Alternative sequence1087 – 109812LSGYM…LCDPK → IAGVFPPFCDYR in isoform B and isoform C.
VSP_038399
Alternative sequence1107 – 11126GYVNNL → CYTNNV in isoform B and isoform C.
VSP_038400

Experimental info

Mutagenesis1331R → A: Has no effect on nervous system function but reduces binding to Pka-C3. Ref.7
Mutagenesis6481G → R in allele sws-5; age-dependent neurodegeneration. Ref.1
Mutagenesis9561G → D in allele sws-4; age-dependent neurodegeneration. Ref.1
Mutagenesis9851S → D: Loss of enzymatic activity. Ref.6
Sequence conflict181I → T in CAB51772. Ref.1
Sequence conflict3141L → F in ABV82201. Ref.4
Sequence conflict4521G → P in CAB51772. Ref.1
Sequence conflict7851R → H in CAB51772. Ref.1
Sequence conflict10761S → H in ABV82201. Ref.4
Sequence conflict1081 – 10833VRS → CRA in ABV82201. Ref.4
Sequence conflict13771T → N in CAB51772. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform A (Long) [UniParc].

Last modified March 25, 2003. Version 2.
Checksum: A7FEE533B1C2B628

FASTA1,425160,573
        10         20         30         40         50         60 
MDVLEMLRAS ASGSYNTIFS DAWCQYVSKQ ITATVYMYFA LVMMSLLFIA WFLYFKRMAR 

        70         80         90        100        110        120 
LRLRDEIARS ISTVTNSSGD MRGLRFRKRD KMLFYGRRML RKMKNVSGQM YSSGKGYKRR 

       130        140        150        160        170        180 
AVMRFARRIL QLRRDNMPLE MRTVEPPAEY LEETIEGSDR VPPDALYMLQ SIRIFGHFEK 

       190        200        210        220        230        240 
PVFLRLCKHT QLLELMAGDY LFKITDPDDS VYIVQSGMIN VYISNADGST LSLKTVRKGE 

       250        260        270        280        290        300 
SVTSLLSFID VLSGNPSYYK TVTAKAIEKS VVIRLPMQAF EEVFQDNPDV MIRVIQVIMI 

       310        320        330        340        350        360 
RLQRVLFTAL RNYLGLNAEL VQNHMRYKSV STMSGPINSQ TSQSSRQAPN GPPMVISQMN 

       370        380        390        400        410        420 
LMQSAVSGTG SSGVSVTVTR PPSSPSRHSR EEHTLSDPNP NPDGSFHGTT NLFTEVHGDA 

       430        440        450        460        470        480 
PNADLFHQQQ QQHSVGNLST RRSSITLMAP DGSHSCLQTP GVTTSIDMRL VQSSAVDSLR 

       490        500        510        520        530        540 
KELGLSEEDS HIIEPFVELR ELEPNVTLIT EGNADDVCVW FVMTGTLAVY QSNQDATRAK 

       550        560        570        580        590        600 
QDKSDMLIHF VHPGEIVGGL AMLTGEASAY TIRSRSITRI AFIRRAAIYQ IMRQRPRIVL 

       610        620        630        640        650        660 
DLGNGVVRRL SPLVRQCDYA LDWIFLESGR AVYRQDESSD STYIVLSGRM RSVITHPGGK 

       670        680        690        700        710        720 
KEIVGEYGKG DLVGIVEMIT ETSRTTTVMA VRDSELAKLP EGLFNAIKLR YPIVVTKLIS 

       730        740        750        760        770        780 
FLSHRFLGSM QTRSGSGAPG APVEANPVTH KYSTVALVPI TDEVPMTPFT YELYHSLCAI 

       790        800        810        820        830        840 
GPVLRLTSDV VRKQLGSNIF EAANEYRLTS WLAQQEDRNI ITLYQCDSSL SAWTQRCMRQ 

       850        860        870        880        890        900 
ADVILIVGLG DRSHLVGKFE REIDRLAMRT QKELVLLYPE ASNAKPANTL SWLNARPWVT 

       910        920        930        940        950        960 
KHHHVLCVKR IFTRKSQYRI NDLYSRVLLS EPNMHSDFSR LARWLTGNSI GLVLGGGGAR 

       970        980        990       1000       1010       1020 
GAAHIGMLKA IQEAGIPVDM VGGVSIGALM GALWCSERNI TTVTQKAREW SKKMTKWFLQ 

      1030       1040       1050       1060       1070       1080 
LLDLTYPITS MFSGREFNKT IHDTFGDVSI EDLWIPYFTL TTDITASCHR IHTNGSLWRY 

      1090       1100       1110       1120       1130       1140 
VRSSMSLSGY MPPLCDPKDG HLLLDGGYVN NLPADVMHNL GAAHIIAIDV GSQDDTDLTN 

      1150       1160       1170       1180       1190       1200 
YGDDLSGWWL LYKKWNPFTS PVKVPDLPDI QSRLAYVSCV RQLEEVKNSD YCEYIRPPID 

      1210       1220       1230       1240       1250       1260 
KYKTLAFGSF DEIRDVGYVF GKNYFESMAK AGRLGRFNQW FNKEPPKRVN HASLNEYTFI 

      1270       1280       1290       1300       1310       1320 
DLAQIVCRLP ETYAVNTAEL FSEDEDCDGY ISEPTTLNTD RRRIQVSRAG NSLSFSETEM 

      1330       1340       1350       1360       1370       1380 
DSDVELDLKL ERKTDKSTQS SPPSNSRSDM RGKEEARHMS NWHWGVKHKD ETGSGATEAT 

      1390       1400       1410       1420 
KTQTGQEQEL QQEQQDQGAT AEQLVDKDKE ENKENRSSPN NETKN 

« Hide

Isoform B (Short) [UniParc].

Checksum: 27425E1327272860
Show »

FASTA34138,784
Isoform C [UniParc].

Checksum: 98FBA2A5E1A368D6
Show »

FASTA1,425160,671

References

« Hide 'large scale' references
[1]"The swiss cheese mutant causes glial hyperwrapping and brain degeneration in Drosophila."
Kretzschmar D., Hasan G., Sharma S., Heisenberg M., Benzer S.
J. Neurosci. 17:7425-7432(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, MUTAGENESIS OF GLY-648 AND GLY-956.
[2]"The genome sequence of Drosophila melanogaster."
Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. expand/collapse author list , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.
Science 287:2185-2195(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Berkeley.
[3]"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review."
Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. expand/collapse author list , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.
Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION, ALTERNATIVE SPLICING.
Strain: Berkeley.
[4]Stapleton M., Carlson J.W., Frise E., Kapadia B., Park S., Wan K.H., Yu C., Celniker S.E.
Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
Strain: Berkeley.
Tissue: Head.
[5]"A Drosophila full-length cDNA resource."
Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E.
Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1052-1425 (ISOFORM A).
Strain: Berkeley.
Tissue: Embryo.
[6]"Loss of swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila."
Muehlig-Versen M., da Cruz A.B., Tschaepe J.-A., Moser M., Buettner R., Athenstaedt K., Glynn P., Kretzschmar D.
J. Neurosci. 25:2865-2873(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF SER-985.
[7]"Swiss cheese, a protein involved in progressive neurodegeneration, acts as a noncanonical regulatory subunit for PKA-C3."
Bettencourt da Cruz A., Wentzell J., Kretzschmar D.
J. Neurosci. 28:10885-10892(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PKA-C3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, MUTAGENESIS OF ARG-133.
[8]"Phosphoproteome analysis of Drosophila melanogaster embryos."
Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.
J. Proteome Res. 7:1675-1682(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-444; SER-453 AND SER-1160, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Embryo.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z97187 mRNA. Translation: CAB51772.1.
AE014298 Genomic DNA. Translation: AAF46305.3.
AE014298 Genomic DNA. Translation: AAN09223.1.
BT030819 mRNA. Translation: ABV82201.1.
AY061431 mRNA. Translation: AAL28979.1. Different initiation.
RefSeqNP_511075.3. NM_078520.3.
NP_727225.1. NM_167141.2.
UniGeneDm.3604.

3D structure databases

ProteinModelPortalQ9U969.
SMRQ9U969. Positions 168-295, 610-714.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9U969. 1 interaction.

Proteomic databases

PaxDbQ9U969.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaFBtr0071125; FBpp0071077; FBgn0003656. [Q9U969-1]
GeneID31716.
KEGGdme:Dmel_CG2212.

Organism-specific databases

CTD31716.
FlyBaseFBgn0003656. sws.

Phylogenomic databases

eggNOGCOG0664.
GeneTreeENSGT00390000002533.
InParanoidQ8IRN7.
KOK14676.
OMANKIHLES.
OrthoDBEOG7QRQT1.
PhylomeDBQ9U969.

Gene expression databases

BgeeQ9U969.

Family and domain databases

Gene3D2.60.120.10. 3 hits.
InterProIPR016035. Acyl_Trfase/lysoPLipase.
IPR018490. cNMP-bd-like.
IPR000595. cNMP-bd_dom.
IPR001423. LysoPLipase_patatin_CS.
IPR002641. Patatin/PLipase_A2-rel.
IPR014710. RmlC-like_jellyroll.
[Graphical view]
PfamPF00027. cNMP_binding. 3 hits.
PF01734. Patatin. 1 hit.
[Graphical view]
SMARTSM00100. cNMP. 3 hits.
[Graphical view]
SUPFAMSSF51206. SSF51206. 3 hits.
SSF52151. SSF52151. 1 hit.
PROSITEPS50042. CNMP_BINDING_3. 3 hits.
PS01237. UPF0028. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi31716.
NextBio774978.

Entry information

Entry nameSWS_DROME
AccessionPrimary (citable) accession number: Q9U969
Secondary accession number(s): A8E6M7 expand/collapse secondary AC list , Q8IRN7, Q95RE9, Q9W3M0
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: March 25, 2003
Last modified: April 16, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Relevant documents

SIMILARITY comments

Index of protein domains and families

Drosophila

Drosophila: entries, gene names and cross-references to FlyBase