ID SPTCS_HUMAN Reviewed; 2443 AA. AC Q96JI7; A8KAX9; B9EK60; F5H3N6; Q4VC11; Q58G86; Q69YG6; Q6NW01; Q8N270; AC Q8TBU9; Q9H734; DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 27-MAR-2024, entry version 165. DE RecName: Full=Spatacsin; DE AltName: Full=Colorectal carcinoma-associated protein; DE AltName: Full=Spastic paraplegia 11 protein; GN Name=SPG11; Synonyms=KIAA1840; 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; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-463. RC TISSUE=Brain; RX PubMed=11347906; DOI=10.1093/dnares/8.2.85; RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XX. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 8:85-95(2001). RN [2] RP SEQUENCE REVISION. 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP SER-463. RC TISSUE=Brain, Spinal cord, Testis, and Urinary bladder; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 84-1205 (ISOFORM 1). RC TISSUE=Melanoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1205-2443 (ISOFORM 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1951-2443 (ISOFORM 1). RC TISSUE=Colon, and Tongue; 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 [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 2386-2443. RC TISSUE=Intestine; RA Ye F., Xiao B., Nan Q.; RT "Isolation of genes which are associated with the colorectal tumor."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP INVOLVEMENT IN SPG11, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17322883; DOI=10.1038/ng1980; RA Stevanin G., Santorelli F.M., Azzedine H., Coutinho P., Chomilier J., RA Denora P.S., Martin E., Ouvrard-Hernandez A.-M., Tessa A., Bouslam N., RA Lossos A., Charles P., Loureiro J.L., Elleuch N., Confavreux C., Cruz V.T., RA Ruberg M., Leguern E., Grid D., Tazir M., Fontaine B., Filla A., RA Bertini E., Durr A., Brice A.; RT "Mutations in SPG11, encoding spatacsin, are a major cause of spastic RT paraplegia with thin corpus callosum."; RL Nat. Genet. 39:366-372(2007). RN [9] RP INVOLVEMENT IN SPG11. RX PubMed=18079167; DOI=10.1093/brain/awm293; RG SPATAX consortium; RA Stevanin G., Azzedine H., Denora P., Boukhris A., Tazir M., Lossos A., RA Rosa A.L., Lerer I., Hamri A., Alegria P., Loureiro J., Tada M., RA Hannequin D., Anheim M., Goizet C., Gonzalez-Martinez V., Le Ber I., RA Forlani S., Iwabuchi K., Meiner V., Uyanik G., Erichsen A.K., Feki I., RA Pasquier F., Belarbi S., Cruz V.T., Depienne C., Truchetto J., RA Garrigues G., Tallaksen C., Tranchant C., Nishizawa M., Vale J., RA Coutinho P., Santorelli F.M., Mhiri C., Brice A., Durr A.; RT "Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia RT with thin corpus callosum, cognitive decline and lower motor neuron RT degeneration."; RL Brain 131:772-784(2008). RN [10] 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 [11] RP INVOLVEMENT IN ALS5. RX PubMed=20110243; DOI=10.1093/brain/awp325; RA Orlacchio A., Babalini C., Borreca A., Patrono C., Massa R., Basaran S., RA Munhoz R.P., Rogaeva E.A., St George-Hyslop P.H., Bernardi G., Kawarai T.; RT "SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral RT sclerosis."; RL Brain 133:591-598(2010). RN [12] RP INTERACTION WITH AP5Z1; AP5B1; AP5S1 AND ZFYVE26. RX PubMed=20613862; DOI=10.1371/journal.pbio.1000408; RA Slabicki M., Theis M., Krastev D.B., Samsonov S., Mundwiller E., RA Junqueira M., Paszkowski-Rogacz M., Teyra J., Heninger A.K., Poser I., RA Prieur F., Truchetto J., Confavreux C., Marelli C., Durr A., RA Camdessanche J.P., Brice A., Shevchenko A., Pisabarro M.T., Stevanin G., RA Buchholz F.; RT "A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene RT associated with hereditary spastic paraplegia."; RL PLoS Biol. 8:E1000408-E1000408(2010). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=24794856; DOI=10.1093/hmg/ddu200; RA Perez-Branguli F., Mishra H.K., Prots I., Havlicek S., Kohl Z., Saul D., RA Rummel C., Dorca-Arevalo J., Regensburger M., Graef D., Sock E., Blasi J., RA Groemer T.W., Schloetzer-Schrehardt U., Winkler J., Winner B.; RT "Dysfunction of spatacsin leads to axonal pathology in SPG11-linked RT hereditary spastic paraplegia."; RL Hum. Mol. Genet. 23:4859-4874(2014). RN [14] 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). RN [15] RP VARIANT SPG11 ILE-1349. RX PubMed=19105190; DOI=10.1002/humu.20945; RA Denora P.S., Schlesinger D., Casali C., Kok F., Tessa A., Boukhris A., RA Azzedine H., Dotti M.T., Bruno C., Truchetto J., Biancheri R., Fedirko E., RA Di Rocco M., Bueno C., Malandrini A., Battini R., Sickl E., de Leva M.F., RA Boespflug-Tanguy O., Silvestri G., Simonati A., Said E., Ferbert A., RA Criscuolo C., Heinimann K., Modoni A., Weber P., Palmeri S., Plasilova M., RA Pauri F., Cassandrini D., Battisti C., Pini A., Tosetti M., Hauser E., RA Masciullo M., Di Fabio R., Piccolo F., Denis E., Cioni G., Massa R., RA Della Giustina E., Calabrese O., Melone M.A., De Michele G., Federico A., RA Bertini E., Durr A., Brockmann K., van der Knaap M.S., Zatz M., Filla A., RA Brice A., Stevanin G., Santorelli F.M.; RT "Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations RT and includes a large scale gene deletion."; RL Hum. Mutat. 30:E500-E519(2009). RN [16] RP INVOLVEMENT IN CMT2X. RX PubMed=26556829; DOI=10.1093/brain/awv320; RA Montecchiani C., Pedace L., Lo Giudice T., Casella A., Mearini M., RA Gaudiello F., Pedroso J.L., Terracciano C., Caltagirone C., Massa R., RA St George-Hyslop P.H., Barsottini O.G., Kawarai T., Orlacchio A.; RT "ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot- RT Marie-Tooth disease."; RL Brain 139:73-85(2016). RN [17] RP VARIANTS SPG11 LEU-412; LEU-1208; ASP-1270; ILE-2298 DEL; PRO-2300 AND RP PRO-2334. RX PubMed=27217339; DOI=10.1093/brain/aww111; RA Kara E., Tucci A., Manzoni C., Lynch D.S., Elpidorou M., Bettencourt C., RA Chelban V., Manole A., Hamed S.A., Haridy N.A., Federoff M., Preza E., RA Hughes D., Pittman A., Jaunmuktane Z., Brandner S., Xiromerisiou G., RA Wiethoff S., Schottlaender L., Proukakis C., Morris H., Warner T., RA Bhatia K.P., Korlipara L.V., Singleton A.B., Hardy J., Wood N.W., RA Lewis P.A., Houlden H.; RT "Genetic and phenotypic characterization of complex hereditary spastic RT paraplegia."; RL Brain 139:1904-1918(2016). CC -!- FUNCTION: May play a role in neurite plasticity by maintaining CC cytoskeleton stability and regulating synaptic vesicle transport. CC {ECO:0000269|PubMed:24794856}. CC -!- SUBUNIT: Interacts with AP5Z1, AP5B1, AP5S1 and ZFYVE26. CC {ECO:0000269|PubMed:20613862}. CC -!- INTERACTION: CC Q96JI7; Q05193: DNM1; NbExp=3; IntAct=EBI-2822128, EBI-713135; CC Q96JI7; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-2822128, EBI-748621; CC Q96JI7; P31946: YWHAB; NbExp=2; IntAct=EBI-2822128, EBI-359815; CC Q96JI7; P62258: YWHAE; NbExp=2; IntAct=EBI-2822128, EBI-356498; CC Q96JI7; P61981: YWHAG; NbExp=2; IntAct=EBI-2822128, EBI-359832; CC Q96JI7; Q04917: YWHAH; NbExp=3; IntAct=EBI-2822128, EBI-306940; CC Q96JI7; P27348: YWHAQ; NbExp=2; IntAct=EBI-2822128, EBI-359854; CC Q96JI7; P63104: YWHAZ; NbExp=2; IntAct=EBI-2822128, EBI-347088; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17322883}. CC Nucleus {ECO:0000269|PubMed:17322883}. Cell projection, axon CC {ECO:0000269|PubMed:24794856}. Cell projection, dendrite CC {ECO:0000269|PubMed:24794856}. Note=Mainly cytoplasmic. CC {ECO:0000269|PubMed:17322883}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96JI7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96JI7-2; Sequence=VSP_025483, VSP_025484; CC Name=3; CC IsoId=Q96JI7-3; Sequence=VSP_045347; CC -!- TISSUE SPECIFICITY: Expressed in all structures of brain, with a high CC expression in cerebellum. Expressed in cortical projection neurons. CC {ECO:0000269|PubMed:17322883, ECO:0000269|PubMed:24794856}. CC -!- DISEASE: Spastic paraplegia 11, autosomal recessive (SPG11) CC [MIM:604360]: A form of spastic paraplegia, a neurodegenerative CC disorder characterized by a slow, gradual, progressive weakness and CC spasticity of the lower limbs. Rate of progression and the severity of CC symptoms are quite variable. Initial symptoms may include difficulty CC with balance, weakness and stiffness in the legs, muscle spasms, and CC dragging the toes when walking. In some forms of the disorder, bladder CC symptoms (such as incontinence) may appear, or the weakness and CC stiffness may spread to other parts of the body. CC {ECO:0000269|PubMed:17322883, ECO:0000269|PubMed:18079167, CC ECO:0000269|PubMed:19105190, ECO:0000269|PubMed:27217339}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Amyotrophic lateral sclerosis 5, juvenile (ALS5) [MIM:602099]: CC A form of amyotrophic lateral sclerosis, a neurodegenerative disorder CC affecting upper motor neurons in the brain and lower motor neurons in CC the brain stem and spinal cord, resulting in fatal paralysis. Sensory CC abnormalities are absent. The pathologic hallmarks of the disease CC include pallor of the corticospinal tract due to loss of motor neurons, CC presence of ubiquitin-positive inclusions within surviving motor CC neurons, and deposition of pathologic aggregates. The etiology of CC amyotrophic lateral sclerosis is likely to be multifactorial, involving CC both genetic and environmental factors. The disease is inherited in 5- CC 10% of the cases. ALS5 is an autosomal recessive, juvenile form CC characterized by onset of upper and lower motor neuron signs before age CC 25. {ECO:0000269|PubMed:20110243}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, 2X (CMT2X) [MIM:616668]: CC An autosomal recessive, axonal form of Charcot-Marie-Tooth disease, a CC disorder of the peripheral nervous system, characterized by progressive CC weakness and atrophy, initially of the peroneal muscles and later of CC the distal muscles of the arms. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathies (designated CMT1 when they are dominantly inherited) and CC primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 CC group are characterized by signs of axonal degeneration in the absence CC of obvious myelin alterations, normal or slightly reduced nerve CC conduction velocities, and progressive distal muscle weakness and CC atrophy. CMT2X patients manifest a slowly progressive, peripheral CC neuropathy affecting the lower limbs and resulting in gait difficulties CC and distal sensory impairment. Some patients also have upper limb CC involvement. {ECO:0000269|PubMed:26556829}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAH24161.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAX54692.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB15065.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC03600.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; AB058743; BAB47469.2; -; mRNA. DR EMBL; AC009996; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC024161; AAH24161.2; ALT_INIT; mRNA. DR EMBL; BC067798; AAH67798.1; -; mRNA. DR EMBL; BC094704; AAH94704.1; -; mRNA. DR EMBL; BC150640; AAI50641.1; -; mRNA. DR EMBL; BC153879; AAI53880.1; -; mRNA. DR EMBL; AL834168; CAH10686.1; -; mRNA. DR EMBL; AK025092; BAB15065.1; ALT_INIT; mRNA. DR EMBL; AK091176; BAC03600.1; ALT_INIT; mRNA. DR EMBL; AY954502; AAX54692.1; ALT_INIT; mRNA. DR CCDS; CCDS10112.1; -. [Q96JI7-1] DR CCDS; CCDS53939.1; -. [Q96JI7-3] DR RefSeq; NP_001153699.1; NM_001160227.1. [Q96JI7-3] DR RefSeq; NP_079413.3; NM_025137.3. [Q96JI7-1] DR AlphaFoldDB; Q96JI7; -. DR BioGRID; 123177; 62. DR CORUM; Q96JI7; -. DR IntAct; Q96JI7; 172. DR MINT; Q96JI7; -. DR STRING; 9606.ENSP00000261866; -. DR iPTMnet; Q96JI7; -. DR PhosphoSitePlus; Q96JI7; -. DR BioMuta; SPG11; -. DR DMDM; 296452946; -. DR EPD; Q96JI7; -. DR jPOST; Q96JI7; -. DR MassIVE; Q96JI7; -. DR MaxQB; Q96JI7; -. DR PaxDb; 9606-ENSP00000261866; -. DR PeptideAtlas; Q96JI7; -. DR ProteomicsDB; 26327; -. DR ProteomicsDB; 76968; -. [Q96JI7-1] DR ProteomicsDB; 76969; -. [Q96JI7-2] DR Pumba; Q96JI7; -. DR Antibodypedia; 11596; 109 antibodies from 23 providers. DR DNASU; 80208; -. DR Ensembl; ENST00000261866.12; ENSP00000261866.7; ENSG00000104133.16. [Q96JI7-1] DR Ensembl; ENST00000535302.6; ENSP00000445278.2; ENSG00000104133.16. [Q96JI7-3] DR Ensembl; ENST00000558319.5; ENSP00000453599.1; ENSG00000104133.16. [Q96JI7-2] DR GeneID; 80208; -. DR KEGG; hsa:80208; -. DR MANE-Select; ENST00000261866.12; ENSP00000261866.7; NM_025137.4; NP_079413.3. DR UCSC; uc001ztx.4; human. [Q96JI7-1] DR AGR; HGNC:11226; -. DR DisGeNET; 80208; -. DR GeneCards; SPG11; -. DR GeneReviews; SPG11; -. DR HGNC; HGNC:11226; SPG11. DR HPA; ENSG00000104133; Low tissue specificity. DR MalaCards; SPG11; -. DR MIM; 602099; phenotype. DR MIM; 604360; phenotype. DR MIM; 610844; gene. DR MIM; 616668; phenotype. DR neXtProt; NX_Q96JI7; -. DR OpenTargets; ENSG00000104133; -. DR Orphanet; 466775; Autosomal recessive Charcot-Marie-Tooth disease type 2X. DR Orphanet; 2822; Autosomal recessive spastic paraplegia type 11. DR Orphanet; 300605; Juvenile amyotrophic lateral sclerosis. DR PharmGKB; PA36058; -. DR VEuPathDB; HostDB:ENSG00000104133; -. DR eggNOG; KOG1884; Eukaryota. DR GeneTree; ENSGT00390000016791; -. DR HOGENOM; CLU_001081_0_0_1; -. DR InParanoid; Q96JI7; -. DR OMA; AQWWDQL; -. DR OrthoDB; 8431at2759; -. DR PhylomeDB; Q96JI7; -. DR TreeFam; TF325171; -. DR PathwayCommons; Q96JI7; -. DR SignaLink; Q96JI7; -. DR BioGRID-ORCS; 80208; 14 hits in 1157 CRISPR screens. DR ChiTaRS; SPG11; human. DR GeneWiki; SPG11; -. DR GenomeRNAi; 80208; -. DR Pharos; Q96JI7; Tbio. DR PRO; PR:Q96JI7; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q96JI7; Protein. DR Bgee; ENSG00000104133; Expressed in bronchial epithelial cell and 205 other cell types or tissues. DR ExpressionAtlas; Q96JI7; baseline and differential. DR GO; GO:0030424; C:axon; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; IBA:GO_Central. DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0045202; C:synapse; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IDA:MGI. DR GO; GO:1905037; P:autophagosome organization; IDA:MGI. DR GO; GO:0008088; P:axo-dendritic transport; IMP:UniProtKB. DR GO; GO:0048675; P:axon extension; IBA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; IMP:UniProtKB. DR GO; GO:0033344; P:cholesterol efflux; IEA:Ensembl. DR GO; GO:0021957; P:corticospinal tract morphogenesis; IEA:Ensembl. DR GO; GO:0051668; P:localization within membrane; IEA:Ensembl. DR GO; GO:0007040; P:lysosome organization; IDA:MGI. DR GO; GO:0007613; P:memory; IEA:Ensembl. DR GO; GO:0061744; P:motor behavior; IEA:Ensembl. DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl. DR GO; GO:0007528; P:neuromuscular junction development; IEA:Ensembl. DR GO; GO:0090389; P:phagosome-lysosome fusion involved in apoptotic cell clearance; IEA:Ensembl. DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl. DR GO; GO:2001256; P:regulation of store-operated calcium entry; IEA:Ensembl. DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:Ensembl. DR GO; GO:0048489; P:synaptic vesicle transport; IMP:UniProtKB. DR GO; GO:0090659; P:walking behavior; IEA:Ensembl. DR InterPro; IPR028103; Spatacsin. DR InterPro; IPR028107; Spatacsin_C_dom. DR PANTHER; PTHR13650:SF0; SPATACSIN; 1. DR PANTHER; PTHR13650; UNCHARACTERIZED; 1. DR Pfam; PF14649; Spatacsin_C; 1. DR Genevisible; Q96JI7; HS. PE 1: Evidence at protein level; KW Alternative splicing; Amyotrophic lateral sclerosis; Cell projection; KW Charcot-Marie-Tooth disease; Cytoplasm; Hereditary spastic paraplegia; KW Neurodegeneration; Neuropathy; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..2443 FT /note="Spatacsin" FT /id="PRO_0000287467" FT MOD_RES 1955 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q3UHA3" FT VAR_SEQ 1956..2069 FT /note="TSSLDSQKFVTVPSSNEVVTNLEVLTSKCLHGKNYCRQVLCLYDLAKELGCS FT YTDVAAQDGEAMLRKILASQQPDRCKRAQAFISTQGLKPDTVAELVAEEVTRELLTSSQ FT GTG -> R (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045347" FT VAR_SEQ 2070..2079 FT /note="HKQMFNPTEE -> ALPPGDSQPL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_025483" FT VAR_SEQ 2080..2443 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_025484" FT VARIANT 396 FT /note="Y -> C (in dbSNP:rs3759875)" FT /id="VAR_032307" FT VARIANT 412 FT /note="S -> L (in SPG11; uncertain significance; FT dbSNP:rs312262723)" FT /evidence="ECO:0000269|PubMed:27217339" FT /id="VAR_078057" FT VARIANT 463 FT /note="F -> S (in dbSNP:rs3759871)" FT /evidence="ECO:0000269|PubMed:11347906, FT ECO:0000269|PubMed:15489334" FT /id="VAR_032308" FT VARIANT 1208 FT /note="P -> L (in SPG11; uncertain significance; FT dbSNP:rs779830116)" FT /evidence="ECO:0000269|PubMed:27217339" FT /id="VAR_078058" FT VARIANT 1270 FT /note="V -> D (in SPG11; uncertain significance; FT dbSNP:rs1555451521)" FT /evidence="ECO:0000269|PubMed:27217339" FT /id="VAR_078059" FT VARIANT 1349 FT /note="F -> I (in SPG11; dbSNP:rs1567149547)" FT /evidence="ECO:0000269|PubMed:19105190" FT /id="VAR_058417" FT VARIANT 2298 FT /note="Missing (in SPG11; uncertain significance)" FT /evidence="ECO:0000269|PubMed:27217339" FT /id="VAR_078060" FT VARIANT 2300 FT /note="L -> P (in SPG11; uncertain significance; FT dbSNP:rs371334506)" FT /evidence="ECO:0000269|PubMed:27217339" FT /id="VAR_078061" FT VARIANT 2334 FT /note="A -> P (in SPG11; uncertain significance; FT dbSNP:rs764647588)" FT /evidence="ECO:0000269|PubMed:27217339" FT /id="VAR_078062" FT CONFLICT 1205 FT /note="N -> K (in Ref. 5; CAH10686)" FT /evidence="ECO:0000305" FT CONFLICT 1674 FT /note="R -> G (in Ref. 6; BAC03600)" FT /evidence="ECO:0000305" FT CONFLICT 2171 FT /note="E -> D (in Ref. 4; AAI50641)" FT /evidence="ECO:0000305" FT CONFLICT 2253 FT /note="D -> G (in Ref. 4; AAH94704)" FT /evidence="ECO:0000305" FT CONFLICT 2378 FT /note="F -> L (in Ref. 6; BAB15065)" FT /evidence="ECO:0000305" SQ SEQUENCE 2443 AA; 278868 MW; 9D00E0BB91931464 CRC64; MAAEEGVASA ASAGGSWGTA AMGRVLPMLL VPVPAEAMGQ LGSRAQLRTQ PEALGSLTAA GSLQVLSLTP GSRGGGRCCL EGPFWHFLWE DSRNSSTPTE KPKLLALGEN YELLIYEFNL KDGRCDATIL YSCSREALQK LIDDQDISIS LLSLRILSFH NNTSLLFINK CVILHIIFPE RDAAIRVLNC FTLPLPAQAV DMIIDTQLCR GILFVLSSLG WIYIFDVVDG TYVAHVDLAL HKEDMCNEQQ QEPAKISSFT SLKVSQDLDV AVIVSSSNSA VALNLNLYFR QHPGHLLCER ILEDLPIQGP KGVDEDDPVN SAYNMKLAKF SFQIDRSWKA QLSSLNETIK NSKLEVSCCA PWFQDILHLE SPESGNHSTS VQSWAFIPQD IMHGQYNVLQ KDHAKTSDPG RSWKIMHISE QEEPIELKCV SVTGFTALFT WEVERMGYTI TLWDLETQGM QCFSLGTKCI PVDSSGDQQL CFVLTENGLS LILFGLTQEE FLNRLMIHGS ASTVDTLCHL NGWGRCSIPI HALEAGIENR QLDTVNFFLK SKENLFNPSS KSSVSDQFDH LSSHLYLRNV EELIPALDLL CSAIRESYSE PQSKHFSEQL LNLTLSFLNN QIKELFIHTE ELDEHLQKGV NILTSYINEL RTFMIKFPWK LTDAIDEYDV HENVPKVKES NIWKKLSFEE VIASAILNNK IPEAQTFFRI DSHSAQKLEE LIGIGLNLVF DNLKKNNIKE ASELLKNMGF DVKGQLLKIC FYTTNKNIRD FLVEILKEKN YFSEKEKRTI DFVHQVEKLY LGHFQENMQI QSFPRYWIKE QDFFKHKSVL DSFLKYDCKD EFNKQDHRIV LNWALWWDQL TQESILLPRI SPEEYKSYSP EALWRYLTAR HDWLNIILWI GEFQTQHSYA SLQQNKWPLL TVDVINQNTS CNNYMRNEIL DKLARNGVFL ASELEDFECF LLRLSRIGGV IQDTLPVQNY KTKEGWDFHS QFILYCLEHS LQHLLYVYLD CYKLSPENCP FLEKKELHEA HPWFEFLVQC RQVASNLTDP KLIFQASLAN AQILIPTNQA SVSSMLLEGH TLLALATTMY SPGGVSQVVQ NEENENCLKK VDPQLLKMAL TPYPKLKTAL FPQCTPPSVL PSDITIYHLI QSLSPFDPSR LFGWQSANTL AIGDAWSHLP HFSSPDLVNK YAIVERLNFA YYLHNGRPSF AFGTFLVQEL IKSKTPKQLI QQVGNEAYVI GLSSFHIPSI GAACVCFLEL LGLDSLKLRV DMKVANIILS YKCRNEDAQY SFIRESVAEK LSKLADGEKT TTEELLVLLE EGTWNSIQQQ EIKRLSSESS SQWALVVQFC RLHNMKLSIS YLRECAKAND WLQFIIHSQL HNYHPAEVKS LIQYFSPVIQ DHLRLAFENL PSVPTSKMDS DQVCNKCPQE LQGSKQEMTD LFEILLQCSE EPDSWHWLLV EAVKQQAPIL SVLASCLQGA SAISCLCVWI ITSVEDNVAT EAMGHIQDST EDHTWNLEDL SVIWRTLLTR QKSKTLIRGF QLFFKDSPLL LVMEMYELCM FFRNYKEAEA KLLEFQKSLE TLNTAATKVH PVIPAMWLED QVCFLLKLML QQCKTQYELG KLLQLFVERE HLFSDGPDVK KLCILCQILK DTSIAINHTI ITSYSIENLQ HECRSILERL QTDGQFALAR RVAELAELPV DNLVIKEITQ EMQTLKHIEQ WSLKQARIDF WKKCHENFKK NSISSKAASS FFSTQAHVAC EHPTGWSSME ERHLLLTLAG HWLAQEDVVP LDKLEELEKQ IWLCRITQHT LGRNQEETEP RFSRQISTSG ELSFDSLASE FSFSKLAALN TSKYLELNSL PSKETCENRL DWKEQESLNF LIGRLLDDGC VHEASRVCRY FHFYNPDVAL VLHCRALASG EASMEDLHPE IHALLQSAEL LEEEAPDIPL RRVHSTSSLD SQKFVTVPSS NEVVTNLEVL TSKCLHGKNY CRQVLCLYDL AKELGCSYTD VAAQDGEAML RKILASQQPD RCKRAQAFIS TQGLKPDTVA ELVAEEVTRE LLTSSQGTGH KQMFNPTEES QTFLQLTTLC QDRTLVGMKL LDKISSVPHG ELSCTTELLI LAHHCFTLTC HMEGIIRVLQ AAHMLTDNHL APSEEYGLVV RLLTGIGRYN EMTYIFDLLH KKHYFEVLMR KKLDPSGTLK TALLDYIKRC RPGDSEKHNM IALCFSMCRE IGENHEAAAR IQLKLIESQP WEDSLKDGHQ LKQLLLKALT LMLDAAESYA KDSCVRQAQH CQRLTKLITL QIHFLNTGQN TMLINLGRHK LMDCILALPR FYQASIVAEA YDFVPDWAEI LYQQVILKGD FNYLEEFKQQ RLLKSSIFEE ISKKYKQHQP TDMVMENLKK LLTYCEDVYL YYKLAYEHKF YEIVNVLLKD PQTGCCLKDM LAG //