ID LRSM1_HUMAN Reviewed; 723 AA. AC Q6UWE0; Q5VVV0; Q8NB40; Q96GT5; Q96MX5; Q96MZ7; DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 10-JUN-2026, entry version 198. DE RecName: Full=E3 ubiquitin-protein ligase LRSAM1 {ECO:0000305}; DE EC=2.3.2.27 {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:23245322}; DE AltName: Full=Leucine-rich repeat and sterile alpha motif-containing protein 1 {ECO:0000303|PubMed:20865121}; DE AltName: Full=RING-type E3 ubiquitin transferase LRSAM1 {ECO:0000305}; DE AltName: Full=Tsg101-associated ligase {ECO:0000303|PubMed:15256501}; DE Short=hTAL {ECO:0000303|PubMed:15256501}; GN Name=LRSAM1 {ECO:0000303|PubMed:20865121}; GN Synonyms=TAL {ECO:0000303|PubMed:15256501}; ORFNames=UNQ6496/PRO21356; 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). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Brain, and Teratocarcinoma; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASP-318. RC TISSUE=Skin; 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 FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF CYS-675; HIS-692 RP AND 649-PRO--PRO-664. RX PubMed=15256501; DOI=10.1101/gad.294904; RA Amit I., Yakir L., Katz M., Zwang Y., Marmor M.D., Citri A., Shtiegman K., RA Alroy I., Tuvia S., Reiss Y., Roubini E., Cohen M., Wides R., Bacharach E., RA Schubert U., Yarden Y.; RT "Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis RT and retrovirus budding."; RL Genes Dev. 18:1737-1752(2004). RN [6] RP INTERACTION WITH TSG101. RX PubMed=17556548; DOI=10.1126/science.1143422; RA Carlton J.G., Martin-Serrano J.; RT "Parallels between cytokinesis and retroviral budding: a role for the ESCRT RT machinery."; RL Science 316:1908-1912(2007). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-234 AND SER-604, 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 [8] RP INVOLVEMENT IN CMT2P. RX PubMed=20865121; DOI=10.1371/journal.pgen.1001081; RA Guernsey D.L., Jiang H., Bedard K., Evans S.C., Ferguson M., Matsuoka M., RA Macgillivray C., Nightingale M., Perry S., Rideout A.L., Orr A., Ludman M., RA Skidmore D.L., Benstead T., Samuels M.E.; RT "Mutation in the gene encoding ubiquitin ligase LRSAM1 in patients with RT Charcot-Marie-Tooth disease."; RL PLoS Genet. 6:E1001081-E1001081(2010). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-604, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=23245322; DOI=10.1016/j.chom.2012.10.019; RA Huett A., Heath R.J., Begun J., Sassi S.O., Baxt L.A., Vyas J.M., RA Goldberg M.B., Xavier R.J.; RT "The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for RT ubiquitin-dependent autophagy of intracellular Salmonella Typhimurium."; RL Cell Host Microbe 12:778-790(2012). RN [12] RP TISSUE SPECIFICITY, AND INVOLVEMENT IN CMT2P. RX PubMed=22012984; DOI=10.1093/hmg/ddr471; RA Weterman M.A., Sorrentino V., Kasher P.R., Jakobs M.E., van Engelen B.G., RA Fluiter K., de Wissel M.B., Sizarov A., Nurnberg G., Nurnberg P., RA Zelcer N., Schelhaas H.J., Baas F.; RT "A frameshift mutation in LRSAM1 is responsible for a dominant hereditary RT polyneuropathy."; RL Hum. Mol. Genet. 21:358-370(2012). RN [13] RP INTERACTION WITH PHF23, FUNCTION, AND UBIQUITINATION. RX PubMed=25484098; DOI=10.4161/auto.36439; RA Wang Z., Hu J., Li G., Qu L., He Q., Lou Y., Song Q., Ma D., Chen Y.; RT "PHF23 (plant homeodomain finger protein 23) negatively regulates cell RT autophagy by promoting ubiquitination and degradation of E3 ligase RT LRSAM1."; RL Autophagy 10:2158-2170(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 CMT2P ARG-694, CHARACTERIZATION OF VARIANT CMT2P ARG-694, RP INTERACTION WITH FUS, AND SUBCELLULAR LOCATION. RX PubMed=27615052; DOI=10.1002/ana.24776; RA Hu B., Arpag S., Zuchner S., Li J.; RT "A novel missense mutation of CMT2P alters transcription machinery."; RL Ann. Neurol. 80:834-845(2016). RN [16] RP VARIANT CMT2P TYR-694, AND CHARACTERIZATION OF VARIANT CMT2P TYR-694. RX PubMed=27686364; DOI=10.1002/ana.24775; RA Peeters K., Palaima P., Pelayo-Negro A.L., Garcia A., Gallardo E., RA Garcia-Barredo R., Mateiu L., Baets J., Menten B., De Vriendt E., RA De Jonghe P., Timmerman V., Infante J., Berciano J., Jordanova A.; RT "Charcot-Marie-Tooth disease type 2G redefined by a novel mutation in RT LRSAM1."; RL Ann. Neurol. 80:823-833(2016). CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates monoubiquitination CC of TSG101 at multiple sites, leading to inactivate the ability of CC TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral CC proteins) cargos (PubMed:15256501). Bacterial recognition protein that CC defends the cytoplasm from invasive pathogens (PubMed:23245322). CC Localizes to several intracellular bacterial pathogens and generates CC the bacteria-associated ubiquitin signal leading to autophagy-mediated CC intracellular bacteria degradation (xenophagy) (PubMed:23245322, CC PubMed:25484098). {ECO:0000269|PubMed:15256501, CC ECO:0000269|PubMed:23245322, ECO:0000269|PubMed:25484098}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:15256501, CC ECO:0000269|PubMed:23245322}; CC -!- PATHWAY: Protein modification; protein ubiquitination. CC {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:23245322}. CC -!- SUBUNIT: Interacts with TSG101 (PubMed:17556548). Interacts with PHF23 CC (PubMed:25484098). Interacts with FUS (PubMed:27615052). CC {ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:25484098, CC ECO:0000269|PubMed:27615052}. CC -!- INTERACTION: CC Q6UWE0; P54253: ATXN1; NbExp=4; IntAct=EBI-720984, EBI-930964; CC Q6UWE0; Q16204: CCDC6; NbExp=3; IntAct=EBI-720984, EBI-1045350; CC Q6UWE0; Q9NPF5: DMAP1; NbExp=3; IntAct=EBI-720984, EBI-399105; CC Q6UWE0; P07098: LIPF; NbExp=2; IntAct=EBI-720984, EBI-3386192; CC Q6UWE0; P54274: TERF1; NbExp=2; IntAct=EBI-720984, EBI-710997; CC Q6UWE0; Q99816: TSG101; NbExp=8; IntAct=EBI-720984, EBI-346882; CC Q6UWE0; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-720984, EBI-10180829; CC Q6UWE0; P61088: UBE2N; NbExp=3; IntAct=EBI-720984, EBI-1052908; CC Q6UWE0; Q6GPH4: XAF1; NbExp=3; IntAct=EBI-720984, EBI-2815120; CC Q6UWE0; Q9H898-2: ZMAT4; NbExp=3; IntAct=EBI-720984, EBI-11529334; CC Q6UWE0; P56959: Fus; Xeno; NbExp=2; IntAct=EBI-720984, EBI-400452; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15256501, CC ECO:0000269|PubMed:27615052}. Note=Displays a punctuate distribution CC and localizes to a submembranal ring (PubMed:15256501). Localizes to CC intracellular bacterial pathogens (PubMed:23245322). CC {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:23245322}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q6UWE0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6UWE0-2; Sequence=VSP_012661; CC Name=3; CC IsoId=Q6UWE0-3; Sequence=VSP_012660; CC -!- TISSUE SPECIFICITY: Highly expressed in adult spinal cord motoneurons CC as well as in fetal spinal cord and muscle tissue. CC {ECO:0000269|PubMed:22012984}. CC -!- DOMAIN: The coiled coil domains interact with the SB domain of TSG101. CC {ECO:0000269|PubMed:15256501}. CC -!- DOMAIN: The PTAP motifs mediate the binding to UEV domains. CC {ECO:0000269|PubMed:15256501}. CC -!- DOMAIN: The LRR domain is necessary and sufficient for localization to CC bacterial targets. {ECO:0000269|PubMed:23245322}. CC -!- DOMAIN: The RING domain is required for ubiquitination. CC {ECO:0000269|PubMed:23245322}. CC -!- PTM: Ubiquitination promoted by PHF23 leads to proteasomal degradation. CC {ECO:0000269|PubMed:25484098}. CC -!- DISEASE: Charcot-Marie-Tooth disease, axonal, type 2P (CMT2P) CC [MIM:614436]: An axonal form of Charcot-Marie-Tooth disease, a disorder CC of the peripheral nervous system, characterized by progressive weakness CC and atrophy, initially of the peroneal muscles and later of the distal CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two CC main groups on the basis of electrophysiologic properties and CC histopathology: primary peripheral demyelinating neuropathies CC (designated CMT1 when they are dominantly inherited) and primary CC peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group CC are characterized by signs of axonal degeneration in the absence of CC obvious myelin alterations, normal or slightly reduced nerve conduction CC velocities, and progressive distal muscle weakness and atrophy. CC {ECO:0000269|PubMed:20865121, ECO:0000269|PubMed:22012984, CC ECO:0000269|PubMed:27615052, ECO:0000269|PubMed:27686364}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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; AY358830; AAQ89189.1; -; mRNA. DR EMBL; AK056203; BAB71119.1; -; mRNA. DR EMBL; AK056305; BAB71144.1; -; mRNA. DR EMBL; AK091589; BAC03703.1; -; mRNA. DR EMBL; AL445222; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009239; AAH09239.1; -; mRNA. DR CCDS; CCDS55347.1; -. [Q6UWE0-2] DR CCDS; CCDS6873.1; -. [Q6UWE0-1] DR RefSeq; NP_001005373.1; NM_001005373.4. [Q6UWE0-1] DR RefSeq; NP_001005374.1; NM_001005374.4. [Q6UWE0-1] DR RefSeq; NP_001177652.1; NM_001190723.3. [Q6UWE0-2] DR RefSeq; NP_001371071.1; NM_001384142.1. [Q6UWE0-1] DR RefSeq; NP_612370.3; NM_138361.5. [Q6UWE0-1] DR AlphaFoldDB; Q6UWE0; -. DR SASBDB; Q6UWE0; -. DR SMR; Q6UWE0; -. DR BioGRID; 124754; 93. DR ELM; Q6UWE0; -. DR FunCoup; Q6UWE0; 826. DR IntAct; Q6UWE0; 154. DR MINT; Q6UWE0; -. DR NDEx; IQUERY-CP-LRSAM1; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000322937; -. DR MoonDB; Q6UWE0; Predicted. DR GlyGen; Q6UWE0; 3 sites, 2 O-linked glycans (1 site). DR iPTMnet; Q6UWE0; -. DR MetOSite; Q6UWE0; -. DR PhosphoSitePlus; Q6UWE0; -. DR BioMuta; LRSAM1; -. DR DMDM; 62511890; -. DR jPOST; Q6UWE0; -. DR MassIVE; Q6UWE0; -. DR PaxDb; 9606-ENSP00000322937; -. DR PeptideAtlas; Q6UWE0; -. DR ProteomicsDB; 67465; -. [Q6UWE0-1] DR ProteomicsDB; 67466; -. [Q6UWE0-2] DR ProteomicsDB; 67467; -. [Q6UWE0-3] DR Pumba; Q6UWE0; -. DR Antibodypedia; 16985; 171 antibodies from 27 providers. DR DNASU; 90678; -. DR Ensembl; ENST00000300417.11; ENSP00000300417.6; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000323301.8; ENSP00000322937.4; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000373322.1; ENSP00000362419.1; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000373324.8; ENSP00000362421.4; ENSG00000148356.16. [Q6UWE0-2] DR Ensembl; ENST00000675448.1; ENSP00000502167.1; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000675883.1; ENSP00000501592.1; ENSG00000148356.16. [Q6UWE0-2] DR Ensembl; ENST00000870579.1; ENSP00000540638.1; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000870581.1; ENSP00000540640.1; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000923145.1; ENSP00000593204.1; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000923146.1; ENSP00000593205.1; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000942478.1; ENSP00000612537.1; ENSG00000148356.16. [Q6UWE0-1] DR Ensembl; ENST00000942483.1; ENSP00000612542.1; ENSG00000148356.16. [Q6UWE0-1] DR GeneID; 90678; -. DR KEGG; hsa:90678; -. DR MANE-Select; ENST00000300417.11; ENSP00000300417.6; NM_001005373.4; NP_001005373.1. DR UCSC; uc004brb.2; human. [Q6UWE0-1] DR AGR; HGNC:25135; -. DR ClinPGx; PA134890010; -. DR CTD; 90678; -. DR DisGeNET; 90678; -. DR GeneCards; LRSAM1; -. DR GeneReviews; LRSAM1; -. DR HGNC; HGNC:25135; LRSAM1. DR HPA; ENSG00000148356; Low tissue specificity. DR MalaCards; LRSAM1; -. DR MIM; 610933; gene. DR MIM; 614436; phenotype. DR OpenTargets; ENSG00000148356; -. DR Orphanet; 300319; Charcot-Marie-Tooth disease type 2P. DR VEuPathDB; HostDB:ENSG00000148356; -. DR eggNOG; KOG0619; Eukaryota. DR GeneTree; ENSGT00930000151044; -. DR HOGENOM; CLU_022990_0_0_1; -. DR InParanoid; Q6UWE0; -. DR OMA; LWCSSEC; -. DR OrthoDB; 1711136at2759; -. DR PAN-GO; Q6UWE0; 0 GO annotations based on evolutionary models. DR PhylomeDB; Q6UWE0; -. DR PathwayCommons; Q6UWE0; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q6UWE0; -. DR SIGNOR; Q6UWE0; -. DR UniPathway; UPA00143; -. DR Agora; ENSG00000148356; -. DR BioGRID-ORCS; 90678; 18 hits in 1198 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; LRSAM1; human. DR GeneWiki; LRSAM1; -. DR GenomeRNAi; 90678; -. DR Pharos; Q6UWE0; Tbio. DR PRO; PR:Q6UWE0; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q6UWE0; protein. DR Bgee; ENSG00000148356; Expressed in apex of heart and 124 other cell types or tissues. DR ExpressionAtlas; Q6UWE0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:GO_Central. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW. DR GO; GO:0045806; P:negative regulation of endocytosis; IMP:UniProtKB. DR GO; GO:2000786; P:positive regulation of autophagosome assembly; IMP:GO_Central. DR GO; GO:1904417; P:positive regulation of xenophagy; IMP:GO_Central. DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB. DR GO; GO:0030163; P:protein catabolic process; IMP:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB. DR GO; GO:0070086; P:ubiquitin-dependent endocytosis; IDA:UniProtKB. DR GO; GO:0046755; P:viral budding; IMP:UniProtKB. DR CDD; cd16515; RING-HC_LRSAM1; 1. DR CDD; cd09523; SAM_TAL; 1. DR FunFam; 3.30.40.10:FF:000252; E3 ubiquitin-protein ligase LRSAM1 isoform 1; 1. DR FunFam; 3.80.10.10:FF:000174; E3 ubiquitin-protein ligase LRSAM1 isoform 1; 1. DR FunFam; 1.10.150.50:FF:000059; E3 ubiquitin-protein ligase LRSAM1 isoform X1; 1. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR001611; Leu-rich_rpt. DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp. DR InterPro; IPR032675; LRR_dom_sf. DR InterPro; IPR050216; LRR_domain-containing. DR InterPro; IPR055414; LRR_R13L4/SHOC2-like. DR InterPro; IPR001660; SAM. DR InterPro; IPR013761; SAM/pointed_sf. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR48051; -; 1. DR PANTHER; PTHR48051:SF47; LEUCINE RICH REPEAT AND STERILE ALPHA MOTIF CONTAINING 1; 1. DR Pfam; PF23598; LRR_14; 1. DR Pfam; PF07647; SAM_2; 1. DR Pfam; PF13920; zf-C3HC4_3; 1. DR SMART; SM00364; LRR_BAC; 4. DR SMART; SM00369; LRR_TYP; 4. DR SMART; SM00454; SAM; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS51450; LRR; 4. DR PROSITE; PS50105; SAM_DOMAIN; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Autophagy; Charcot-Marie-Tooth disease; Coiled coil; KW Cytoplasm; Disease variant; Leucine-rich repeat; Metal-binding; KW Neurodegeneration; Neuropathy; Phosphoprotein; Protein transport; KW Proteomics identification; Reference proteome; Repeat; Transferase; KW Transport; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..723 FT /note="E3 ubiquitin-protein ligase LRSAM1" FT /id="PRO_0000055923" FT REPEAT 30..51 FT /note="LRR 1" FT REPEAT 56..77 FT /note="LRR 2" FT REPEAT 82..103 FT /note="LRR 3" FT REPEAT 105..127 FT /note="LRR 4" FT REPEAT 128..149 FT /note="LRR 5" FT REPEAT 151..172 FT /note="LRR 6" FT DOMAIN 569..632 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT ZN_FING 675..710 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 282..314 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 642..665 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 254..380 FT /evidence="ECO:0000255" FT COILED 510..562 FT /evidence="ECO:0000255" FT MOTIF 649..652 FT /note="PTAP motif 1" FT MOTIF 661..664 FT /note="PTAP motif 2" FT COMPBIAS 291..314 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 234 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 604 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT VAR_SEQ 1..420 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_012660" FT VAR_SEQ 474..500 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_012661" FT VARIANT 318 FT /note="N -> D (in dbSNP:rs1539567)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_021051" FT VARIANT 694 FT /note="C -> R (in CMT2P; abolishes interaction with FUS; FT dbSNP:rs759312530)" FT /evidence="ECO:0000269|PubMed:27615052" FT /id="VAR_077460" FT VARIANT 694 FT /note="C -> Y (in CMT2P; uncertain significance; FT dbSNP:rs886041051)" FT /evidence="ECO:0000269|PubMed:27686364" FT /id="VAR_077461" FT MUTAGEN 649..664 FT /note="Missing: Abolishes interaction with TSG101." FT /evidence="ECO:0000269|PubMed:15256501" FT MUTAGEN 675 FT /note="C->A: Abolishes ubiquitination of TSG101." FT /evidence="ECO:0000269|PubMed:15256501" FT MUTAGEN 692 FT /note="H->A: Abolishes ubiquitination of TSG101." FT /evidence="ECO:0000269|PubMed:15256501" FT CONFLICT 385 FT /note="V -> F (in Ref. 2; BAB71119)" FT /evidence="ECO:0000305" FT CONFLICT 402 FT /note="I -> V (in Ref. 2; BAC03703)" FT /evidence="ECO:0000305" SQ SEQUENCE 723 AA; 83594 MW; 4A59461C92467BB1 CRC64; MPLFFRKRKP SEEARKRLEY QMCLAKEAGA DDILDISKCE LSEIPFGAFA TCKVLQKKVL IVHTNHLTSL LPKSCSLLSL ATIKVLDLHD NQLTALPDDL GQLTALQVLN VERNQLMQLP RSIGNLTQLQ TLNVKDNKLK ELPDTVGELR SLRTLNISGN EIQRLPQMLA HVRTLEMLSL DASAMVYPPR EVCGAGTAAI LQFLCKESGL EYYPPSQYLL PILEQDGIEN SRDSPDGPTD RFSREELEWQ NRFSDYEKRK EQKMLEKLEF ERRLELGQRE HTQLLQQSSS QKDEILQTVK EEQSRLEQGL SEHQRHLNAE RQRLQEQLKQ TEQNISSRIQ KLLQDNQRQK KSSEILKSLE NERIRMEQLM SITQEETESL RRRDVASAMQ QMLTESCKNR LIQMAYESQR QNLVQQACSS MAEMDERFQQ ILSWQQMDQN KAISQILQES AMQKAAFEAL QVKKDLMHRQ IRSQIKLIET ELLQLTQLEL KRKSLDTESL QEMISEQRWA LSSLLQQLLK EKQQREEELR EILTELEAKS ETRQENYWLI QYQRLLNQKP LSLKLQEEGM ERQLVALLEE LSAEHYLPIF AHHRLSLDLL SQMSPGDLAK VGVSEAGLQH EILRRVQELL DAARIQPELK PPMGEVVTPT APQEPPESVR PSAPPAELEV QASECVVCLE REAQMIFLNC GHVCCCQQCC QPLRTCPLCR QDIAQRLRIY HSS //