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 24-JAN-2024, entry version 204. 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 Kidney RC {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; 26. DR IntAct; Q96Q42; 21. DR MINT; Q96Q42; -. DR STRING; 9606.ENSP00000264276; -. DR GlyGen; Q96Q42; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000264276; -. DR PeptideAtlas; Q96Q42; -. DR ProteomicsDB; 77823; -. [Q96Q42-1] DR ProteomicsDB; 77824; -. [Q96Q42-2] DR ProteomicsDB; 77825; -. [Q96Q42-3] DR Pumba; Q96Q42; -. DR Antibodypedia; 34146; 284 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 AGR; HGNC:443; -. DR CTD; 57679; -. DR DisGeNET; 57679; -. DR GeneCards; ALS2; -. DR GeneReviews; ALS2; -. DR HGNC; HGNC:443; ALS2. DR HPA; ENSG00000003393; Tissue enriched (brain). 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 OrthoDB; 3740287at2759; -. 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; 11 hits in 1152 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 181 other cell types or tissues. DR ExpressionAtlas; Q96Q42; baseline and differential. 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: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:0001662; P:behavioral fear response; IEA:Ensembl. DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central. DR GO; GO:0007032; P:endosome organization; NAS:UniProtKB. 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:0001881; P:receptor recycling; IEA:Ensembl. DR GO; GO:0051036; P:regulation of endosome size; IEP:UniProtKB. DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl. DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl. DR CDD; cd13269; PH_alsin; 1. DR Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1. DR Gene3D; 2.20.110.10; Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain; 3. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 2.130.10.30; Regulator of chromosome condensation 1/beta-lactamase-inhibitor protein II; 2. DR Gene3D; 1.20.1050.80; VPS9 domain; 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 PANTHER; PTHR46089:SF3; ALSIN; 1. DR PANTHER; PTHR46089; ALSIN HOMOLOG; 1. 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; SSF48065; DBL homology domain (DH-domain); 1. DR SUPFAM; SSF82185; Histone H3 K4-specific methyltransferase SET7/9 N-terminal domain; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF50985; RCC1/BLIP-II; 2. DR SUPFAM; SSF109993; VPS9 domain; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS00626; RCC1_2; 2. DR PROSITE; PS50012; RCC1_3; 5. DR PROSITE; PS51205; VPS9; 1. DR Genevisible; Q96Q42; HS. 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 //