LRSM1_HUMAN
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 03-AUG-2022, entry version 180.
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; 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 2P (CMT2P) [MIM:614436]: An axonal
CC form of Charcot-Marie-Tooth disease, a disorder of the peripheral
CC nervous system, characterized by progressive weakness and atrophy,
CC initially of the peroneal muscles and later of the distal muscles of
CC the arms. Charcot-Marie-Tooth disease is classified in two main groups
CC on the basis of electrophysiologic properties and histopathology:
CC primary peripheral demyelinating neuropathies (designated CMT1 when
CC they are dominantly inherited) and primary peripheral axonal
CC neuropathies (CMT2). Neuropathies of the CMT2 group are characterized
CC by signs of axonal degeneration in the absence of obvious myelin
CC alterations, normal or slightly reduced nerve conduction velocities,
CC 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.
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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_001005373.3. [Q6UWE0-1]
DR RefSeq; NP_001005374.1; NM_001005374.3. [Q6UWE0-1]
DR RefSeq; NP_001177652.1; NM_001190723.2. [Q6UWE0-2]
DR RefSeq; NP_612370.3; NM_138361.5. [Q6UWE0-1]
DR RefSeq; XP_016870772.1; XM_017015283.1.
DR AlphaFoldDB; Q6UWE0; -.
DR SMR; Q6UWE0; -.
DR BioGRID; 124754; 79.
DR ELM; Q6UWE0; -.
DR IntAct; Q6UWE0; 101.
DR MINT; Q6UWE0; -.
DR STRING; 9606.ENSP00000322937; -.
DR MoonDB; Q6UWE0; Predicted.
DR iPTMnet; Q6UWE0; -.
DR MetOSite; Q6UWE0; -.
DR PhosphoSitePlus; Q6UWE0; -.
DR BioMuta; LRSAM1; -.
DR DMDM; 62511890; -.
DR EPD; Q6UWE0; -.
DR jPOST; Q6UWE0; -.
DR MassIVE; Q6UWE0; -.
DR MaxQB; Q6UWE0; -.
DR PaxDb; Q6UWE0; -.
DR PeptideAtlas; Q6UWE0; -.
DR PRIDE; Q6UWE0; -.
DR ProteomicsDB; 67465; -. [Q6UWE0-1]
DR ProteomicsDB; 67466; -. [Q6UWE0-2]
DR ProteomicsDB; 67467; -. [Q6UWE0-3]
DR Antibodypedia; 16985; 177 antibodies from 27 providers.
DR DNASU; 90678; -.
DR Ensembl; ENST00000300417.11; ENSP00000300417.6; ENSG00000148356.15. [Q6UWE0-1]
DR Ensembl; ENST00000323301.8; ENSP00000322937.4; ENSG00000148356.15. [Q6UWE0-1]
DR Ensembl; ENST00000373322.1; ENSP00000362419.1; ENSG00000148356.15. [Q6UWE0-1]
DR Ensembl; ENST00000373324.8; ENSP00000362421.4; ENSG00000148356.15. [Q6UWE0-2]
DR Ensembl; ENST00000675448.1; ENSP00000502167.1; ENSG00000148356.15. [Q6UWE0-1]
DR Ensembl; ENST00000675883.1; ENSP00000501592.1; ENSG00000148356.15. [Q6UWE0-2]
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 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 neXtProt; NX_Q6UWE0; -.
DR OpenTargets; ENSG00000148356; -.
DR Orphanet; 300319; Charcot-Marie-Tooth disease type 2P.
DR PharmGKB; PA134890010; -.
DR VEuPathDB; HostDB:ENSG00000148356; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00930000151044; -.
DR HOGENOM; CLU_022990_0_0_1; -.
DR InParanoid; Q6UWE0; -.
DR OMA; KSLENEX; -.
DR PhylomeDB; Q6UWE0; -.
DR TreeFam; TF329645; -.
DR PathwayCommons; Q6UWE0; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q6UWE0; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 90678; 16 hits in 1119 CRISPR screens.
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 122 other tissues.
DR ExpressionAtlas; Q6UWE0; baseline and differential.
DR Genevisible; Q6UWE0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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: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 Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF07647; SAM_2; 1.
DR SMART; SM00369; LRR_TYP; 4.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 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 Reference proteome; Repeat; Transferase; Transport; Ubl conjugation;
KW 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 295..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; unknown pathological 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
