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Q9U969

- SWS_DROME

UniProt

Q9U969 - SWS_DROME

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Protein

Neuropathy target esterase sws

Gene

sws

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.3 Publications

Catalytic activityi

2-lysophosphatidylcholine + H2O = glycerophosphocholine + a carboxylate.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei985 – 9851

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi174 – 301128cNMP 1Add
BLAST
Nucleotide bindingi482 – 609128cNMP 2Add
BLAST
Nucleotide bindingi598 – 727130cNMP 3Add
BLAST

GO - Molecular functioni

  1. lysophospholipase activity Source: UniProtKB

GO - Biological processi

  1. glial cell apoptotic process Source: UniProtKB
  2. membrane lipid metabolic process Source: FlyBase
  3. membrane organization Source: FlyBase
  4. nervous system development Source: UniProtKB-KW
  5. neuron apoptotic process Source: FlyBase
  6. phosphatidylcholine metabolic process Source: FlyBase
  7. sensory perception of smell Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase

Keywords - Biological processi

Neurogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Neuropathy target esterase sws
Alternative name(s):
Swiss cheese (EC:3.1.1.5)
Short name:
DSWS
Gene namesi
Name:sws
ORF Names:CG2212
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
ProteomesiUP000000803: Chromosome X

Organism-specific databases

FlyBaseiFBgn0003656. sws.

Subcellular locationi

Endoplasmic reticulum membrane 2 Publications; Single-pass type I membrane protein 2 Publications
Note: Sws tethers Pka-C3 to the membrane.

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: UniProtKB
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Disruption phenotypei

Progressive degeneration of the adult nervous system, associated with apoptotic cell death, glial hyperwrapping, and neuronal apoptosis. Also, vacuolization in the neuropil.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi133 – 1331R → A: Has no effect on nervous system function but reduces binding to Pka-C3. 1 Publication
Mutagenesisi648 – 6481G → R in allele sws-5; age-dependent neurodegeneration. 1 Publication
Mutagenesisi956 – 9561G → D in allele sws-4; age-dependent neurodegeneration. 1 Publication
Mutagenesisi985 – 9851S → D: Loss of enzymatic activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14251425Neuropathy target esterase swsPRO_0000172527Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei444 – 4441Phosphoserine1 Publication
Modified residuei453 – 4531Phosphoserine1 Publication
Modified residuei1160 – 11601Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9U969.

Expressioni

Tissue specificityi

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.3 Publications

Developmental stagei

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

Gene expression databases

BgeeiQ9U969.

Interactioni

Subunit structurei

Interacts with Pka-C3; interaction inhibits the catalytic function of Pka-C3 and the esterase activity of sws.1 Publication

Protein-protein interaction databases

IntActiQ9U969. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ9U969.
SMRiQ9U969. Positions 610-714.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3434LumenalSequence AnalysisAdd
BLAST
Topological domaini56 – 14251370CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei35 – 5521HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini952 – 1118167PatatinAdd
BLAST

Sequence similaritiesi

Belongs to the NTE family.Curated
Contains 3 cyclic nucleotide-binding domains.PROSITE-ProRule annotation
Contains 1 patatin domain.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0664.
GeneTreeiENSGT00390000002533.
InParanoidiQ9U969.
KOiK14676.
OMAiNKIHLES.
OrthoDBiEOG7QRQT1.
PhylomeDBiQ9U969.

Family and domain databases

Gene3Di2.60.120.10. 3 hits.
InterProiIPR016035. 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]
PfamiPF00027. cNMP_binding. 3 hits.
PF01734. Patatin. 1 hit.
[Graphical view]
SMARTiSM00100. cNMP. 3 hits.
[Graphical view]
SUPFAMiSSF51206. SSF51206. 3 hits.
SSF52151. SSF52151. 1 hit.
PROSITEiPS50042. CNMP_BINDING_3. 3 hits.
PS01237. UPF0028. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform A (identifier: Q9U969-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MDVLEMLRAS ASGSYNTIFS DAWCQYVSKQ ITATVYMYFA LVMMSLLFIA
60 70 80 90 100
WFLYFKRMAR LRLRDEIARS ISTVTNSSGD MRGLRFRKRD KMLFYGRRML
110 120 130 140 150
RKMKNVSGQM YSSGKGYKRR AVMRFARRIL QLRRDNMPLE MRTVEPPAEY
160 170 180 190 200
LEETIEGSDR VPPDALYMLQ SIRIFGHFEK PVFLRLCKHT QLLELMAGDY
210 220 230 240 250
LFKITDPDDS VYIVQSGMIN VYISNADGST LSLKTVRKGE SVTSLLSFID
260 270 280 290 300
VLSGNPSYYK TVTAKAIEKS VVIRLPMQAF EEVFQDNPDV MIRVIQVIMI
310 320 330 340 350
RLQRVLFTAL RNYLGLNAEL VQNHMRYKSV STMSGPINSQ TSQSSRQAPN
360 370 380 390 400
GPPMVISQMN LMQSAVSGTG SSGVSVTVTR PPSSPSRHSR EEHTLSDPNP
410 420 430 440 450
NPDGSFHGTT NLFTEVHGDA PNADLFHQQQ QQHSVGNLST RRSSITLMAP
460 470 480 490 500
DGSHSCLQTP GVTTSIDMRL VQSSAVDSLR KELGLSEEDS HIIEPFVELR
510 520 530 540 550
ELEPNVTLIT EGNADDVCVW FVMTGTLAVY QSNQDATRAK QDKSDMLIHF
560 570 580 590 600
VHPGEIVGGL AMLTGEASAY TIRSRSITRI AFIRRAAIYQ IMRQRPRIVL
610 620 630 640 650
DLGNGVVRRL SPLVRQCDYA LDWIFLESGR AVYRQDESSD STYIVLSGRM
660 670 680 690 700
RSVITHPGGK KEIVGEYGKG DLVGIVEMIT ETSRTTTVMA VRDSELAKLP
710 720 730 740 750
EGLFNAIKLR YPIVVTKLIS FLSHRFLGSM QTRSGSGAPG APVEANPVTH
760 770 780 790 800
KYSTVALVPI TDEVPMTPFT YELYHSLCAI GPVLRLTSDV VRKQLGSNIF
810 820 830 840 850
EAANEYRLTS WLAQQEDRNI ITLYQCDSSL SAWTQRCMRQ ADVILIVGLG
860 870 880 890 900
DRSHLVGKFE REIDRLAMRT QKELVLLYPE ASNAKPANTL SWLNARPWVT
910 920 930 940 950
KHHHVLCVKR IFTRKSQYRI NDLYSRVLLS EPNMHSDFSR LARWLTGNSI
960 970 980 990 1000
GLVLGGGGAR GAAHIGMLKA IQEAGIPVDM VGGVSIGALM GALWCSERNI
1010 1020 1030 1040 1050
TTVTQKAREW SKKMTKWFLQ LLDLTYPITS MFSGREFNKT IHDTFGDVSI
1060 1070 1080 1090 1100
EDLWIPYFTL TTDITASCHR IHTNGSLWRY VRSSMSLSGY MPPLCDPKDG
1110 1120 1130 1140 1150
HLLLDGGYVN NLPADVMHNL GAAHIIAIDV GSQDDTDLTN YGDDLSGWWL
1160 1170 1180 1190 1200
LYKKWNPFTS PVKVPDLPDI QSRLAYVSCV RQLEEVKNSD YCEYIRPPID
1210 1220 1230 1240 1250
KYKTLAFGSF DEIRDVGYVF GKNYFESMAK AGRLGRFNQW FNKEPPKRVN
1260 1270 1280 1290 1300
HASLNEYTFI DLAQIVCRLP ETYAVNTAEL FSEDEDCDGY ISEPTTLNTD
1310 1320 1330 1340 1350
RRRIQVSRAG NSLSFSETEM DSDVELDLKL ERKTDKSTQS SPPSNSRSDM
1360 1370 1380 1390 1400
RGKEEARHMS NWHWGVKHKD ETGSGATEAT KTQTGQEQEL QQEQQDQGAT
1410 1420
AEQLVDKDKE ENKENRSSPN NETKN
Length:1,425
Mass (Da):160,573
Last modified:March 25, 2003 - v2
Checksum:iA7FEE533B1C2B628
GO
Isoform B (identifier: Q9U969-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:341
Mass (Da):38,784
Checksum:i27425E1327272860
GO
Isoform C (identifier: Q9U969-3) [UniParc]FASTAAdd to Basket

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.

Show »
Length:1,425
Mass (Da):160,671
Checksum:i98FBA2A5E1A368D6
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti18 – 181I → T in CAB51772. (PubMed:9295388)Curated
Sequence conflicti314 – 3141L → F in ABV82201. 1 PublicationCurated
Sequence conflicti452 – 4521G → P in CAB51772. (PubMed:9295388)Curated
Sequence conflicti785 – 7851R → H in CAB51772. (PubMed:9295388)Curated
Sequence conflicti1076 – 10761S → H in ABV82201. 1 PublicationCurated
Sequence conflicti1081 – 10833VRS → CRA in ABV82201. 1 PublicationCurated
Sequence conflicti1377 – 13771T → N in CAB51772. (PubMed:9295388)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 10841084Missing in isoform B. CuratedVSP_038398Add
BLAST
Alternative sequencei1087 – 109812LSGYM…LCDPK → IAGVFPPFCDYR in isoform B and isoform C. 1 PublicationVSP_038399Add
BLAST
Alternative sequencei1107 – 11126GYVNNL → CYTNNV in isoform B and isoform C. 1 PublicationVSP_038400

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
RefSeqiNP_511075.3. NM_078520.3. [Q9U969-1]
NP_727225.1. NM_167141.3. [Q9U969-2]
UniGeneiDm.3604.

Genome annotation databases

EnsemblMetazoaiFBtr0071125; FBpp0071077; FBgn0003656. [Q9U969-1]
GeneIDi31716.
KEGGidme:Dmel_CG2212.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
RefSeqi NP_511075.3. NM_078520.3. [Q9U969-1 ]
NP_727225.1. NM_167141.3. [Q9U969-2 ]
UniGenei Dm.3604.

3D structure databases

ProteinModelPortali Q9U969.
SMRi Q9U969. Positions 610-714.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q9U969. 1 interaction.

Proteomic databases

PaxDbi Q9U969.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblMetazoai FBtr0071125 ; FBpp0071077 ; FBgn0003656 . [Q9U969-1 ]
GeneIDi 31716.
KEGGi dme:Dmel_CG2212.

Organism-specific databases

CTDi 31716.
FlyBasei FBgn0003656. sws.

Phylogenomic databases

eggNOGi COG0664.
GeneTreei ENSGT00390000002533.
InParanoidi Q9U969.
KOi K14676.
OMAi NKIHLES.
OrthoDBi EOG7QRQT1.
PhylomeDBi Q9U969.

Miscellaneous databases

GenomeRNAii 31716.
NextBioi 774978.

Gene expression databases

Bgeei Q9U969.

Family and domain databases

Gene3Di 2.60.120.10. 3 hits.
InterProi IPR016035. 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 ]
Pfami PF00027. cNMP_binding. 3 hits.
PF01734. Patatin. 1 hit.
[Graphical view ]
SMARTi SM00100. cNMP. 3 hits.
[Graphical view ]
SUPFAMi SSF51206. SSF51206. 3 hits.
SSF52151. SSF52151. 1 hit.
PROSITEi PS50042. CNMP_BINDING_3. 3 hits.
PS01237. UPF0028. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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. 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.

Entry informationi

Entry nameiSWS_DROME
AccessioniPrimary (citable) accession number: Q9U969
Secondary accession number(s): A8E6M7
, Q8IRN7, Q95RE9, Q9W3M0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: March 25, 2003
Last modified: October 29, 2014
This is version 114 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3