ALS2_HUMAN
ID ALS2_HUMAN Reviewed; 1657 AA.
AC Q96Q42; Q53TT1; Q53TV2; Q8N1E0; Q96PC4; Q96Q41; Q9H973; Q9HCK9;
DT 09-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Alsin;
DE AltName: Full=Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 6 protein;
DE AltName: Full=Amyotrophic lateral sclerosis 2 protein;
GN Name=ALS2; Synonyms=ALS2CR6, KIAA1563;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:BAB69014.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS ARG-102 AND LYS-1406, AND
RP INVOLVEMENT IN JPLS.
RX PubMed=11586297; DOI=10.1038/ng1001-160;
RA Yang Y., Hentati A., Deng H.-X., Dabbagh O., Sasaki T., Hirano M.,
RA Hung W.-Y., Ouahchi K., Yan J., Azim A.C., Cole N., Gascon G., Yagmour A.,
RA Ben-Hamida M., Pericak-Vance M., Hentati F., Siddique T.;
RT "The gene encoding alsin, a protein with three guanine-nucleotide exchange
RT factor domains, is mutated in a form of recessive amyotrophic lateral
RT sclerosis.";
RL Nat. Genet. 29:160-165(2001).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INVOLVEMENT IN ALS2, AND
RP VARIANT MET-368.
RC TISSUE=Brain {ECO:0000269|PubMed:11586298};
RX PubMed=11586298; DOI=10.1038/ng1001-166;
RA Hadano S., Hand C.K., Osuga H., Yanagisawa Y., Otomo A., Devon R.S.,
RA Miyamoto N., Showguchi-Miyata J., Okada Y., Singaraja R., Figlewicz D.A.,
RA Kwiatkowski T., Hosler B.A., Sagie T., Skaug J., Nasir J., Brown R.H. Jr.,
RA Scherer S.W., Rouleau G.A., Hayden M.R., Ikeda J.-E.;
RT "A gene encoding a putative GTPase regulator is mutated in familial
RT amyotrophic lateral sclerosis 2.";
RL Nat. Genet. 29:166-173(2001).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-368.
RC TISSUE=Brain {ECO:0000269|PubMed:10997877};
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [4] {ECO:0000305}
RP SEQUENCE REVISION TO 303-304.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [7] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT MET-368.
RC TISSUE=Colon {ECO:0000269|PubMed:15489334}, and
RC Kidney {ECO:0000269|PubMed:15489334};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP SUBUNIT, AND INTERACTION WITH ALS2CL.
RX PubMed=17239822; DOI=10.1016/j.bbrc.2006.12.229;
RA Suzuki-Utsunomiya K., Hadano S., Otomo A., Kunita R., Mizumura H.,
RA Osuga H., Ikeda J.-E.;
RT "ALS2CL, a novel ALS2-interactor, modulates ALS2-mediated endosome
RT dynamics.";
RL Biochem. Biophys. Res. Commun. 354:491-497(2007).
RN [10] {ECO:0000305}
RP INVOLVEMENT IN IAHSP.
RX PubMed=12145748; DOI=10.1086/342359;
RA Eymard-Pierre E., Lesca G., Dollet S., Santorelli F.M., di Capua M.,
RA Bertini E., Boespflug-Tanguy O.;
RT "Infantile-onset ascending hereditary spastic paralysis is associated with
RT mutations in the alsin gene.";
RL Am. J. Hum. Genet. 71:518-527(2002).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483 AND SER-492, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483 AND SER-492, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-533, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483 AND SER-492, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466; SER-483 AND SER-492, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-465; SER-466 AND SER-483, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: May act as a GTPase regulator. Controls survival and growth
CC of spinal motoneurons (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Forms a heteromeric complex with ALS2CL. Interacts with
CC ALS2CL. {ECO:0000269|PubMed:17239822}.
CC -!- INTERACTION:
CC Q96Q42; P20339: RAB5A; NbExp=2; IntAct=EBI-1044902, EBI-399437;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:11586298};
CC IsoId=Q96Q42-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:11586298};
CC IsoId=Q96Q42-2; Sequence=VSP_050521, VSP_050522;
CC Name=3 {ECO:0000305};
CC IsoId=Q96Q42-3; Sequence=VSP_050523, VSP_050524;
CC -!- DISEASE: Amyotrophic lateral sclerosis 2 (ALS2) [MIM:205100]: A
CC neurodegenerative disorder affecting upper motor neurons in the brain
CC and lower motor neurons in the brain stem and spinal cord, resulting in
CC fatal paralysis. Sensory abnormalities are absent. The pathologic
CC hallmarks of the disease include pallor of the corticospinal tract due
CC to loss of motor neurons, presence of ubiquitin-positive inclusions
CC within surviving motor neurons, and deposition of pathologic
CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to
CC be multifactorial, involving both genetic and environmental factors.
CC The disease is inherited in 5-10% of the cases.
CC {ECO:0000269|PubMed:11586298}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Juvenile primary lateral sclerosis (JPLS) [MIM:606353]: A
CC neurodegenerative disorder which is closely related to but clinically
CC distinct from amyotrophic lateral sclerosis. It is a progressive
CC paralytic disorder which results from dysfunction of the upper motor
CC neurons while the lower neurons are unaffected.
CC {ECO:0000269|PubMed:11586297}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Infantile-onset ascending spastic paralysis (IAHSP)
CC [MIM:607225]: Characterized by progressive spasticity and weakness of
CC limbs. {ECO:0000269|PubMed:12145748}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13389.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Alsod; Note=ALS genetic mutations db;
CC URL="https://alsod.ac.uk/";
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; AF391100; AAL14103.1; -; mRNA.
DR EMBL; AB053305; BAB69014.1; -; mRNA.
DR EMBL; AB053306; BAB69015.1; -; mRNA.
DR EMBL; AB046783; BAB13389.2; ALT_INIT; mRNA.
DR EMBL; AK023024; BAB14362.1; -; mRNA.
DR EMBL; AC007242; AAX93181.1; -; Genomic_DNA.
DR EMBL; AC007279; AAY15058.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70291.1; -; Genomic_DNA.
DR EMBL; BC029174; AAH29174.1; -; mRNA.
DR CCDS; CCDS42800.1; -. [Q96Q42-1]
DR CCDS; CCDS46492.1; -. [Q96Q42-2]
DR RefSeq; NP_001129217.1; NM_001135745.1. [Q96Q42-2]
DR RefSeq; NP_065970.2; NM_020919.3. [Q96Q42-1]
DR RefSeq; XP_006712717.1; XM_006712654.2. [Q96Q42-1]
DR AlphaFoldDB; Q96Q42; -.
DR BioGRID; 121708; 24.
DR IntAct; Q96Q42; 22.
DR MINT; Q96Q42; -.
DR STRING; 9606.ENSP00000264276; -.
DR iPTMnet; Q96Q42; -.
DR PhosphoSitePlus; Q96Q42; -.
DR BioMuta; ALS2; -.
DR DMDM; 296434394; -.
DR EPD; Q96Q42; -.
DR jPOST; Q96Q42; -.
DR MassIVE; Q96Q42; -.
DR MaxQB; Q96Q42; -.
DR PaxDb; Q96Q42; -.
DR PeptideAtlas; Q96Q42; -.
DR PRIDE; Q96Q42; -.
DR ProteomicsDB; 77823; -. [Q96Q42-1]
DR ProteomicsDB; 77824; -. [Q96Q42-2]
DR ProteomicsDB; 77825; -. [Q96Q42-3]
DR Antibodypedia; 34146; 261 antibodies from 36 providers.
DR DNASU; 57679; -.
DR Ensembl; ENST00000264276.11; ENSP00000264276.6; ENSG00000003393.16. [Q96Q42-1]
DR Ensembl; ENST00000409632.7; ENSP00000386384.3; ENSG00000003393.16. [Q96Q42-2]
DR Ensembl; ENST00000467448.5; ENSP00000429223.1; ENSG00000003393.16. [Q96Q42-2]
DR Ensembl; ENST00000679435.1; ENSP00000505218.1; ENSG00000003393.16. [Q96Q42-1]
DR Ensembl; ENST00000679503.1; ENSP00000505968.1; ENSG00000003393.16. [Q96Q42-2]
DR Ensembl; ENST00000679516.1; ENSP00000505187.1; ENSG00000003393.16. [Q96Q42-1]
DR Ensembl; ENST00000680163.1; ENSP00000505092.1; ENSG00000003393.16. [Q96Q42-1]
DR Ensembl; ENST00000680188.1; ENSP00000505665.1; ENSG00000003393.16. [Q96Q42-2]
DR Ensembl; ENST00000680861.1; ENSP00000505043.1; ENSG00000003393.16. [Q96Q42-1]
DR GeneID; 57679; -.
DR KEGG; hsa:57679; -.
DR MANE-Select; ENST00000264276.11; ENSP00000264276.6; NM_020919.4; NP_065970.2.
DR UCSC; uc002uyo.4; human. [Q96Q42-1]
DR CTD; 57679; -.
DR DisGeNET; 57679; -.
DR GeneCards; ALS2; -.
DR GeneReviews; ALS2; -.
DR HGNC; HGNC:443; ALS2.
DR HPA; ENSG00000003393; Low tissue specificity.
DR MalaCards; ALS2; -.
DR MIM; 205100; phenotype.
DR MIM; 606352; gene.
DR MIM; 606353; phenotype.
DR MIM; 607225; phenotype.
DR neXtProt; NX_Q96Q42; -.
DR OpenTargets; ENSG00000003393; -.
DR Orphanet; 293168; Infantile-onset ascending hereditary spastic paralysis.
DR Orphanet; 300605; Juvenile amyotrophic lateral sclerosis.
DR Orphanet; 247604; Juvenile primary lateral sclerosis.
DR PharmGKB; PA24732; -.
DR VEuPathDB; HostDB:ENSG00000003393; -.
DR eggNOG; KOG0231; Eukaryota.
DR eggNOG; KOG1426; Eukaryota.
DR GeneTree; ENSGT00940000155861; -.
DR HOGENOM; CLU_003333_0_0_1; -.
DR InParanoid; Q96Q42; -.
DR OMA; WFSGKPH; -.
DR PhylomeDB; Q96Q42; -.
DR TreeFam; TF331793; -.
DR PathwayCommons; Q96Q42; -.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR SignaLink; Q96Q42; -.
DR BioGRID-ORCS; 57679; 9 hits in 1076 CRISPR screens.
DR ChiTaRS; ALS2; human.
DR GeneWiki; ALS2; -.
DR GenomeRNAi; 57679; -.
DR Pharos; Q96Q42; Tbio.
DR PRO; PR:Q96Q42; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q96Q42; protein.
DR Bgee; ENSG00000003393; Expressed in cerebellum and 180 other tissues.
DR ExpressionAtlas; Q96Q42; baseline and differential.
DR Genevisible; Q96Q42; HS.
DR GO; GO:0005813; C:centrosome; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0031982; C:vesicle; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IDA:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0008219; P:cell death; IEA:Ensembl.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0007032; P:endosome organization; IGI:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0007041; P:lysosomal transport; IDA:MGI.
DR GO; GO:0007528; P:neuromuscular junction development; IEA:Ensembl.
DR GO; GO:0048812; P:neuron projection morphogenesis; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IC:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:MGI.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0016601; P:Rac protein signal transduction; IEA:Ensembl.
DR GO; GO:0001881; P:receptor recycling; IEA:Ensembl.
DR GO; GO:0051036; P:regulation of endosome size; IEP:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl.
DR Gene3D; 1.20.1050.80; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.130.10.30; -; 2.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR003409; MORN.
DR InterPro; IPR011993; PH-like_dom_sf.
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; 8.
DR Pfam; PF00415; RCC1; 4.
DR Pfam; PF00621; RhoGEF; 1.
DR Pfam; PF02204; VPS9; 1.
DR PRINTS; PR00633; RCCNDNSATION.
DR SMART; SM00698; MORN; 8.
DR SUPFAM; SSF109993; SSF109993; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR SUPFAM; SSF50985; SSF50985; 2.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS00626; RCC1_2; 2.
DR PROSITE; PS50012; RCC1_3; 5.
DR PROSITE; PS51205; VPS9; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Amyotrophic lateral sclerosis;
KW Guanine-nucleotide releasing factor; Neurodegeneration; Phosphoprotein;
KW Reference proteome; Repeat.
FT CHAIN 1..1657
FT /note="Alsin"
FT /id="PRO_0000080903"
FT REPEAT 59..108
FT /note="RCC1 1"
FT /evidence="ECO:0000305"
FT REPEAT 109..167
FT /note="RCC1 2"
FT /evidence="ECO:0000305"
FT REPEAT 169..218
FT /note="RCC1 3"
FT /evidence="ECO:0000305"
FT REPEAT 525..576
FT /note="RCC1 4"
FT /evidence="ECO:0000305"
FT REPEAT 578..627
FT /note="RCC1 5"
FT /evidence="ECO:0000305"
FT DOMAIN 690..885
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 901..1007
FT /note="PH"
FT /evidence="ECO:0000305"
FT REPEAT 1049..1071
FT /note="MORN 1"
FT REPEAT 1072..1094
FT /note="MORN 2"
FT REPEAT 1100..1122
FT /note="MORN 3"
FT REPEAT 1123..1145
FT /note="MORN 4"
FT REPEAT 1151..1173
FT /note="MORN 5"
FT REPEAT 1175..1197
FT /note="MORN 6"
FT REPEAT 1198..1220
FT /note="MORN 7"
FT REPEAT 1221..1244
FT /note="MORN 8"
FT DOMAIN 1513..1657
FT /note="VPS9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00550"
FT REGION 432..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 465
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 466
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 510
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P0C5Y8"
FT MOD_RES 533
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1335
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0C5Y8"
FT VAR_SEQ 372..396
FT /note="PLLEEAIPNLHSPPTTSTSALNSLV -> VPAQFYKIKVCLELNCMGFSLET
FT LK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11586298,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_050521"
FT VAR_SEQ 397..1657
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11586298,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_050522"
FT VAR_SEQ 785..807
FT /note="YCTSITNFLVMGGFQLLAKPAID -> QVSSPVSCSISAGLFCQGEQLLN
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_050523"
FT VAR_SEQ 808..1657
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_050524"
FT VARIANT 94
FT /note="I -> V (in dbSNP:rs3219154)"
FT /id="VAR_036747"
FT VARIANT 102
FT /note="H -> R (in dbSNP:rs1416065347)"
FT /evidence="ECO:0000269|PubMed:11586297"
FT /id="VAR_015655"
FT VARIANT 159
FT /note="E -> K (in dbSNP:rs3219155)"
FT /id="VAR_036748"
FT VARIANT 368
FT /note="V -> M (in dbSNP:rs3219156)"
FT /evidence="ECO:0000269|PubMed:10997877,
FT ECO:0000269|PubMed:11586297, ECO:0000269|PubMed:11586298,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_015656"
FT VARIANT 1255
FT /note="S -> F (in dbSNP:rs10206276)"
FT /id="VAR_036749"
FT VARIANT 1406
FT /note="R -> K (in dbSNP:rs1559033861)"
FT /evidence="ECO:0000269|PubMed:11586297"
FT /id="VAR_015657"
FT CONFLICT 69
FT /note="P -> L (in Ref. 1; AAL14103 and 5; BAB14362)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="W -> C (in Ref. 8; AAH29174)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1657 AA; 183634 MW; 0DF8AC7B259F255A CRC64;
MDSKKRSSTE AEGSKERGLV HIWQAGSFPI TPERLPGWGG KTVLQAALGV KHGVLLTEDG
EVYSFGTLPW RSGPVEICPS SPILENALVG QYVITVATGS FHSGAVTDNG VAYMWGENSA
GQCAVANQQY VPEPNPVSIA DSEASPLLAV RILQLACGEE HTLALSISRE IWAWGTGCQL
GLITTAFPVT KPQKVEHLAG RVVLQVACGA FHSLALVQCL PSQDLKPVPE RCNQCSQLLI
TMTDKEDHVI ISDSHCCPLG VTLTESQAEN HASTALSPST ETLDRQEEVF ENTLVANDQS
VATELNAVSA QITSSDAMSS QQNVMGTTEI SSARNIPSYP DTQAVNEYLR KLSDHSVRED
SEHGEKPVPS QPLLEEAIPN LHSPPTTSTS ALNSLVVSCA SAVGVRVAAT YEAGALSLKK
VMNFYSTTPC ETGAQAGSSA IGPEGLKDSR EEQVKQESMQ GKKSSSLVDI REEETEGGSR
RLSLPGLLSQ VSPRLLRKAA RVKTRTVVLT PTYSGEADAL LPSLRTEVWT WGKGKEGQLG
HGDVLPRLQP LCVKCLDGKE VIHLEAGGYH SLALTAKSQV YSWGSNTFGQ LGHSDFPTTV
PRLAKISSEN GVWSIAAGRD YSLFLVDTED FQPGLYYSGR QDPTEGDNLP ENHSGSKTPV
LLSCSKLGYI SRVTAGKDSY LALVDKNIMG YIASLHELAT TERRFYSKLS DIKSQILRPL
LSLENLGTTT TVQLLQEVAS RFSKLCYLIG QHGASLSSFL HGVKEARSLV ILKHSSLFLD
SYTEYCTSIT NFLVMGGFQL LAKPAIDFLN KNQELLQDLS EVNDENTQLM EILNTLFFLP
IRRLHNYAKV LLKLATCFEV ASPEYQKLQD SSSCYECLAL HLGRKRKEAE YTLGFWKTFP
GKMTDSLRKP ERRLLCESSN RALSLQHAGR FSVNWFILFN DALVHAQFST HHVFPLATLW
AEPLSEEAGG VNGLKITTPE EQFTLISSTP QEKTKWLRAI SQAVDQALRG MSDLPPYGSG
SSVQRQEPPI SRSAKYTFYK DPRLKDATYD GRWLSGKPHG RGVLKWPDGK MYSGMFRNGL
EDGYGEYRIP NKAMNKEDHY VGHWKEGKMC GQGVYSYASG EVFEGCFQDN MRHGHGLLRS
GKLTSSSPSM FIGQWVMDKK AGYGVFDDIT RGEKYMGMWQ DDVCQGNGVV VTQFGLYYEG
NFHLNKMMGN GVLLSEDDTI YEGEFSDDWT LSGKGTLTMP NGDYIEGYFS GEWGSGIKIT
GTYFKPSLYE SDKDRPKVFR KLGNLAVPAD EKWKAVFDEC WRQLGCEGPG QGEVWKAWDN
IAVALTTSRR QHRDSPEILS RSQTQTLESL EFIPQHVGAF SVEKYDDIRK YLIKACDTPL
HPLGRLVETL VAVYRMTYVG VGANRRLLQE AVKEIKSYLK RIFQLVRFLF PELPEEGSTI
PLSAPLPTER KSFCTGKSDS RSESPEPGYV VTSSGLLLPV LLPRLYPPLF MLYALDNDRE
EDIYWECVLR LNKQPDIALL GFLGVQRKFW PATLSILGES KKVLPTTKDA CFASAVECLQ
QISTTFTPSD KLKVIQQTFE EISQSVLASL HEDFLWSMDD LFPVFLYVVL RARIRNLGSE
VHLIEDLMDP YLQHGEQGIM FTTLKACYYQ IQREKLN
