ALS2_DROME
ID ALS2_DROME Reviewed; 1486 AA.
AC Q9VNZ8;
DT 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Alsin homolog {ECO:0000305};
DE AltName: Full=Amyotrophic lateral sclerosis 2 protein homolog {ECO:0000303|PubMed:24702731};
GN Name=Als2 {ECO:0000312|FlyBase:FBgn0037116};
GN ORFNames=CG7158 {ECO:0000312|FlyBase:FBgn0037116};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:AAL28951.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL28951.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAL28951.1};
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP PRO-1425 AND LEU-1439.
RX PubMed=24702731; DOI=10.1111/gtc.12146;
RA Takayama Y., Itoh R.E., Tsuyama T., Uemura T.;
RT "Age-dependent deterioration of locomotion in Drosophila melanogaster
RT deficient in the homologue of amyotrophic lateral sclerosis 2.";
RL Genes Cells 19:464-477(2014).
CC -!- FUNCTION: Has guanine nucleotide exchange factor (GEF) activity towards
CC Rab5. Promotes the exchange of GDP to GTP, converting inactive GDP-
CC bound Rab5 into its active GTP-bound form.
CC {ECO:0000269|PubMed:24702731}.
CC -!- TISSUE SPECIFICITY: In the embryo, expressed in a wide range of tissues
CC including the epidermis and the ventral nerve cord.
CC {ECO:0000269|PubMed:24702731}.
CC -!- DISRUPTION PHENOTYPE: Deterioration of locomotion in adults with
CC climbing ability strongly depressed. {ECO:0000269|PubMed:24702731}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE014296; AAF51764.1; -; Genomic_DNA.
DR EMBL; AY061403; AAL28951.1; -; mRNA.
DR RefSeq; NP_649347.1; NM_141090.3.
DR AlphaFoldDB; Q9VNZ8; -.
DR SMR; Q9VNZ8; -.
DR IntAct; Q9VNZ8; 4.
DR STRING; 7227.FBpp0078116; -.
DR PaxDb; Q9VNZ8; -.
DR PRIDE; Q9VNZ8; -.
DR DNASU; 40410; -.
DR EnsemblMetazoa; FBtr0078462; FBpp0078116; FBgn0037116.
DR GeneID; 40410; -.
DR KEGG; dme:Dmel_CG7158; -.
DR UCSC; CG7158-RA; d. melanogaster.
DR CTD; 57679; -.
DR FlyBase; FBgn0037116; Als2.
DR VEuPathDB; VectorBase:FBgn0037116; -.
DR eggNOG; KOG0231; Eukaryota.
DR eggNOG; KOG1426; Eukaryota.
DR HOGENOM; CLU_004393_0_0_1; -.
DR InParanoid; Q9VNZ8; -.
DR OMA; CIAVYMS; -.
DR OrthoDB; 37470at2759; -.
DR PhylomeDB; Q9VNZ8; -.
DR Reactome; R-DME-9013149; RAC1 GTPase cycle.
DR BioGRID-ORCS; 40410; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 40410; -.
DR PRO; PR:Q9VNZ8; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0037116; Expressed in spermathecum and 27 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0031982; C:vesicle; ISS:FlyBase.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:FlyBase.
DR GO; GO:0031267; F:small GTPase binding; IBA:GO_Central.
DR GO; GO:0045022; P:early endosome to late endosome transport; IMP:FlyBase.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0007032; P:endosome organization; IBA:GO_Central.
DR GO; GO:0035011; P:melanotic encapsulation of foreign target; IMP:FlyBase.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:FlyBase.
DR GO; GO:0043087; P:regulation of GTPase activity; IMP:FlyBase.
DR GO; GO:0032483; P:regulation of Rab protein signal transduction; ISM:FlyBase.
DR Gene3D; 1.20.1050.80; -; 1.
DR Gene3D; 2.130.10.30; -; 1.
DR InterPro; IPR003409; MORN.
DR InterPro; IPR009091; RCC1/BLIP-II.
DR InterPro; IPR000408; Reg_chr_condens.
DR InterPro; IPR003123; VPS9.
DR InterPro; IPR037191; VPS9_dom_sf.
DR Pfam; PF02493; MORN; 6.
DR Pfam; PF02204; VPS9; 1.
DR SMART; SM00698; MORN; 5.
DR SUPFAM; SSF109993; SSF109993; 1.
DR SUPFAM; SSF50985; SSF50985; 1.
DR PROSITE; PS00626; RCC1_2; 1.
DR PROSITE; PS50012; RCC1_3; 2.
DR PROSITE; PS51205; VPS9; 1.
PE 1: Evidence at protein level;
KW GTPase activation; Guanine-nucleotide releasing factor; Reference proteome;
KW Repeat.
FT CHAIN 1..1486
FT /note="Alsin homolog"
FT /id="PRO_0000436307"
FT REPEAT 147..201
FT /note="RCC1 1"
FT /evidence="ECO:0000255"
FT REPEAT 256..307
FT /note="RCC1 2"
FT /evidence="ECO:0000255"
FT REPEAT 308..363
FT /note="RCC1 3"
FT /evidence="ECO:0000255"
FT REPEAT 744..765
FT /note="MORN 1"
FT /evidence="ECO:0000255"
FT REPEAT 766..784
FT /note="MORN 2"
FT /evidence="ECO:0000255"
FT REPEAT 789..804
FT /note="MORN 3"
FT /evidence="ECO:0000255"
FT REPEAT 817..832
FT /note="MORN 4"
FT /evidence="ECO:0000255"
FT REPEAT 839..853
FT /note="MORN 5"
FT /evidence="ECO:0000255"
FT REPEAT 863..884
FT /note="MORN 6"
FT /evidence="ECO:0000255"
FT DOMAIN 1333..1486
FT /note="VPS9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00550"
FT MUTAGEN 1425
FT /note="P->A: Reduced GEF activity."
FT /evidence="ECO:0000269|PubMed:24702731"
FT MUTAGEN 1439
FT /note="L->A: Reduced GEF activity."
FT /evidence="ECO:0000269|PubMed:24702731"
SQ SEQUENCE 1486 AA; 165886 MW; C46DF7E7928E1204 CRC64;
MASAADDSAL GGQEERESFT IYHEGRELQL HWRGLPPLQR FPASRICSNA GGELLLLTTD
HALYSAKLQA NREHMDLQLL RTDVVDMDFC SGSQELFVVL TNGSVQRQAT GSGRDVGHPH
AWQTLGFDPL ELHAEGVRIR RVCCSAQGVV FVGASGETYV MGSCGEVFKA EQQPRHMRLY
EEGKELLDLA AGNEHFVMLV APYNLADDAL QLSVASAKEE PEDERASVKS ISSGHSERSV
AANTRHLLHQ GYALLHTQLF TFGASNNGLL GSGDHIRRAN VMRLQKLDSM GVCSIAAGLE
HTVARTLDGR LYHWGLNNHS QLGEDVSSPM EITITENTAA LPIEQNSALE ATCGDYHTLL
LNASGQIHSL QPAPPMRHLQ QSSTYAQTLL QLQLGAAWPR QLRLLMCSGG YTLQNQRQFQ
RQYHYYLSHL QSQLQLLLKH RQAVQTLEIW QRQSALEPLS ALGPLLINWE RILCLLVATL
HSLEGFYRAD FVQPADLLFI CHYKEYIDLF DGYTKAYCDV FSVNGFGEAV VAITGLSSPL
AELNEESYVT RLFQQPFSIY QLFVQFMELL VRTQSEYGEH RVAWSEFARH SCISQELAVN
TKDFWSSNDR NPRIVQFRGR HRRVILTSAL VPLKLVTSGI SRSSNSFILF SDFLCQVSGN
SLYSYPLTTL WVWTEGDSLR LTTPEKSFLV STRSQEMRKV WLDQLQSSII ASLGKPLGSP
VPSYRSTGYE FSREHPKFSR VKACGTWRKG VLHGNCYLEY PDGSVYCGEL QHGIIEGFGK
MVIPTTGLYV GNFKGGRFHG HGVYEMHCKD SPESEVYEGN FCEGLFHGHG VMRNNRYIYV
GEYQANARSG YGVIEDLVSG DKYMGMFADN KRSGIGSCIT NRGDYFEGSF SGDDLTGSGV
AVFENDYYYE GELTLLGPNG RGEYYMPSGD ACGGSGAMGT GEFDDTCELI GNKMFGQLSG
TWDTVRIQAG ELVLNRRFPK YPSSLGRQVV DHNRKWRSLF NNFESDLANC TASTSSSGGN
QSAGTLRKSS KPTLSTAQIW NCIAVYMSKQ RAREGTKPGN YFNNILLSLP LPQKTSSPLA
KARTTTSALS KLQTEAASAL DFLGFPPRRI QSQEALNSKP GGLQRADSLI SMGHNTSRDL
DNSSLASFQL DQSLMNSTVN GDESSTFNES FSKLSHNNNN SISKHMNNID CSITSTTSTT
SAVLDQVPSF GMALVLTEQD VTSIRLYLEQ AFKDRHHPLY VLNERIANCF HYSYGYWKVK
PTPILAKQAM REWESISRRI YRFVRKMFPA LPEELCQMEG SREVISHITL LYPLVLSEGI
YSTLFVLYAN KYSRKDEMYR QNLNLAEKLK DQELVELMGH ESFLHNVMLD PKFVESVQTL
KELQEKFSPQ DMLTVIQRST QLLTEAYEHA MAANAAQLNA DNMIPLTMLT MLRAAVPHLG
AELALLDDLT GGPNFQAEMN GMAGYCYTTL KAAYEHVTSR ALQKIP
