ID   LRSM1_MOUSE             Reviewed;         727 AA.
AC   Q80ZI6;
DT   01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   27-MAR-2024, entry version 164.
DE   RecName: Full=E3 ubiquitin-protein ligase LRSAM1 {ECO:0000250|UniProtKB:Q6UWE0};
DE            EC=2.3.2.27 {ECO:0000250|UniProtKB:Q6UWE0};
DE   AltName: Full=Leucine-rich repeat and sterile alpha motif-containing protein 1 {ECO:0000250|UniProtKB:Q6UWE0};
DE   AltName: Full=RING-type E3 ubiquitin transferase LRSAM1 {ECO:0000305};
DE   AltName: Full=Tsg101-associated ligase {ECO:0000250|UniProtKB:Q6UWE0};
GN   Name=Lrsam1 {ECO:0000250|UniProtKB:Q6UWE0};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Olfactory epithelium;
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   [2]
RP   TISSUE SPECIFICITY.
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   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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 (viral proteins)
CC       cargos (By similarity). Bacterial recognition protein that defends the
CC       cytoplasm from invasive pathogens (By similarity). Localizes to several
CC       intracellular bacterial pathogens and generates the bacteria-associated
CC       ubiquitin signal leading to autophagy-mediated intracellular bacteria
CC       degradation (xenophagy) (By similarity).
CC       {ECO:0000250|UniProtKB:Q6UWE0}.
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:0000250|UniProtKB:Q6UWE0};
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC       {ECO:0000250|UniProtKB:Q6UWE0}.
CC   -!- SUBUNIT: Interacts with TSG101. Interacts with PHF23. Interacts with
CC       FUS. {ECO:0000250|UniProtKB:Q6UWE0}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q6UWE0}.
CC       Note=Displays a punctuate distribution and localizes to a submembranal
CC       ring (PubMed:15256501). Localizes to intracellular bacterial pathogens
CC       (By similarity). {ECO:0000250|UniProtKB:Q6UWE0}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:15256501}.
CC   -!- DOMAIN: The coiled coil domains interact with the SB domain of TSG101.
CC       {ECO:0000250|UniProtKB:Q6UWE0}.
CC   -!- DOMAIN: The PTAP motifs mediate the binding to UEV domains.
CC       {ECO:0000250|UniProtKB:Q6UWE0}.
CC   -!- DOMAIN: The LRR domain is necessary and sufficient for localization to
CC       bacterial targets. {ECO:0000250|UniProtKB:Q6UWE0}.
CC   -!- DOMAIN: The RING domain is required for ubiquitination.
CC       {ECO:0000250|UniProtKB:Q6UWE0}.
CC   -!- PTM: Ubiquitination promoted by PHF23 leads to proteasomal degradation.
CC       {ECO:0000250|UniProtKB:Q6UWE0}.
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; BC049146; AAH49146.1; -; mRNA.
DR   CCDS; CCDS15935.1; -.
DR   RefSeq; NP_955006.1; NM_199302.2.
DR   RefSeq; XP_006498032.1; XM_006497969.3.
DR   RefSeq; XP_006498033.1; XM_006497970.3.
DR   RefSeq; XP_006498034.1; XM_006497971.3.
DR   RefSeq; XP_006498035.1; XM_006497972.3.
DR   AlphaFoldDB; Q80ZI6; -.
DR   SMR; Q80ZI6; -.
DR   BioGRID; 230680; 4.
DR   IntAct; Q80ZI6; 2.
DR   STRING; 10090.ENSMUSP00000108825; -.
DR   iPTMnet; Q80ZI6; -.
DR   PhosphoSitePlus; Q80ZI6; -.
DR   SwissPalm; Q80ZI6; -.
DR   EPD; Q80ZI6; -.
DR   MaxQB; Q80ZI6; -.
DR   PaxDb; 10090-ENSMUSP00000108825; -.
DR   PeptideAtlas; Q80ZI6; -.
DR   ProteomicsDB; 292118; -.
DR   Pumba; Q80ZI6; -.
DR   Antibodypedia; 16985; 199 antibodies from 27 providers.
DR   DNASU; 227738; -.
DR   Ensembl; ENSMUST00000028132.14; ENSMUSP00000028132.8; ENSMUSG00000026792.17.
DR   Ensembl; ENSMUST00000113200.8; ENSMUSP00000108825.2; ENSMUSG00000026792.17.
DR   GeneID; 227738; -.
DR   KEGG; mmu:227738; -.
DR   UCSC; uc008jhd.2; mouse.
DR   AGR; MGI:2684789; -.
DR   MGI; MGI:2684789; Lrsam1.
DR   VEuPathDB; HostDB:ENSMUSG00000026792; -.
DR   eggNOG; KOG0619; Eukaryota.
DR   GeneTree; ENSGT00930000151044; -.
DR   HOGENOM; CLU_022990_0_0_1; -.
DR   InParanoid; Q80ZI6; -.
DR   OMA; DFWLLQY; -.
DR   OrthoDB; 1043058at2759; -.
DR   PhylomeDB; Q80ZI6; -.
DR   TreeFam; TF329645; -.
DR   Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 227738; 2 hits in 78 CRISPR screens.
DR   ChiTaRS; Lrsam1; mouse.
DR   PRO; PR:Q80ZI6; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q80ZI6; Protein.
DR   Bgee; ENSMUSG00000026792; Expressed in embryonic brain and 76 other cell types or tissues.
DR   ExpressionAtlas; Q80ZI6; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:GO_Central.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR   GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR   GO; GO:0045806; P:negative regulation of endocytosis; ISS:UniProtKB.
DR   GO; GO:2000786; P:positive regulation of autophagosome assembly; ISS:GO_Central.
DR   GO; GO:1904417; P:positive regulation of xenophagy; ISS:GO_Central.
DR   GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR   GO; GO:0030163; P:protein catabolic process; ISS:UniProtKB.
DR   GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR   GO; GO:0070086; P:ubiquitin-dependent endocytosis; ISS:UniProtKB.
DR   GO; GO:0046755; P:viral budding; ISS:UniProtKB.
DR   CDD; cd16515; RING-HC_LRSAM1; 1.
DR   CDD; cd09523; SAM_TAL; 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; 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:SF46; LEUCINE RICH REPEAT AND STERILE ALPHA MOTIF CONTAINING 1; 1.
DR   Pfam; PF13855; LRR_8; 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   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.
DR   Genevisible; Q80ZI6; MM.
PE   1: Evidence at protein level;
KW   Autophagy; Coiled coil; Cytoplasm; Leucine-rich repeat; Metal-binding;
KW   Phosphoprotein; Protein transport; Reference proteome; Repeat; Transferase;
KW   Transport; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..727
FT                   /note="E3 ubiquitin-protein ligase LRSAM1"
FT                   /id="PRO_0000055924"
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..126
FT                   /note="LRR 4"
FT   REPEAT          128..150
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         679..714
FT                   /note="RING-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   REGION          227..248
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          241..382
FT                   /evidence="ECO:0000255"
FT   COILED          469..547
FT                   /evidence="ECO:0000255"
FT   MOTIF           653..656
FT                   /note="PTAP motif 1"
FT   MOTIF           665..668
FT                   /note="PTAP motif 2"
FT   MOD_RES         234
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6UWE0"
FT   MOD_RES         604
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6UWE0"
SQ   SEQUENCE   727 AA;  83976 MW;  561B6FE6F730ADAE CRC64;
     MPLFFRKRKP SEEARKRLEY QMCLAKEAGA DDILDISKCE LSEIPFGAFA TCKVLQKKVL
     IVHTNHLTSL LPKSCSLLSL VTIKVLDLHE NQLTALPDDM GQLTVLQVLN VERNQLTHLP
     RSIGNLLQLQ TLNVKDNKLK ELPDTLGELR SLRTLDISEN EIQRLPQMLA HVRTLETLSL
     NALAMVYPPP EVCGAGTAAV QQFLCKESGL DYYPPSQYLL PVLEQDGAEN TQDSPDGPAS
     RFSREEAEWQ NRFSDYEKRK EQKMLEKLEF ERRLDLGQRE HAELLQQSHS HKDEILQTVK
     QEQTRLEQDL SERQRCLDAE RQQLQEQLKQ TEQSIASRIQ RLLQDNQRQK KSSEILKSLE
     NERIRMEQLM SITQEETENL RQREIAAAMQ QMLTESCKSR LIQMAYESQR QSLAQQACSS
     MAEMDKRFQQ ILSWQQMDQN KAISQILQES VMQKAAFEAL QVKKDLMHRQ IRNQIRLIET
     ELLQLTQLEL KRKSLDTETL QEMVSEQRWA LSNLLQQLLK EKKQREEELH GILAELEAKS
     ETKQENYWLI QYQRLLNQKP LSLKLQEEGM ERRLVALLVE LSAEHYLPLF AHHRISLDML
     SRMSPGDLAK VGVSEAGLQH EILRRAQDLL AVPRVQPELK PLENEVLGAL EPPTAPRELQ
     ESVRPSAPPA ELDMPTSECV VCLEREAQMV FLTCGHVCCC QQCCQPLRTC PLCRQEISQR
     LRIYHSS
//