Q6UWE0 · LRSM1_HUMAN

  • Protein
    E3 ubiquitin-protein ligase LRSAM1
  • Gene
    LRSAM1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral proteins) cargos (PubMed:15256501).
Bacterial recognition protein that defends the cytoplasm from invasive pathogens (PubMed:23245322).
Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (PubMed:23245322, PubMed:25484098).

Catalytic activity

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)

Pathway

Protein modification; protein ubiquitination.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentmembrane
Molecular Functionmetal ion binding
Molecular Functionubiquitin protein ligase activity
Molecular Functionubiquitin-protein transferase activity
Biological Processautophagy
Biological Processnegative regulation of endocytosis
Biological Processpositive regulation of autophagosome assembly
Biological Processpositive regulation of xenophagy
Biological Processprotein autoubiquitination
Biological Processprotein catabolic process
Biological Processprotein polyubiquitination
Biological Processubiquitin-dependent endocytosis
Biological Processviral budding

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    E3 ubiquitin-protein ligase LRSAM1
  • EC number
  • Alternative names
    • Leucine-rich repeat and sterile alpha motif-containing protein 1
    • RING-type E3 ubiquitin transferase LRSAM1
    • Tsg101-associated ligase
      (hTAL
      )

Gene names

    • Name
      LRSAM1
    • Synonyms
      TAL
    • ORF names
      UNQ6496/PRO21356

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q6UWE0
  • Secondary accessions
    • Q5VVV0
    • Q8NB40
    • Q96GT5
    • Q96MX5
    • Q96MZ7

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Note: Displays a punctuate distribution and localizes to a submembranal ring (PubMed:15256501).
Localizes to intracellular bacterial pathogens (PubMed:23245322).

Keywords

Disease & Variants

Involvement in disease

Charcot-Marie-Tooth disease, axonal, 2P (CMT2P)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy.
  • See also
    MIM:614436
Natural variants in CMT2P
Variant IDPosition(s)ChangeDescription
VAR_077460694C>Rin CMT2P; abolishes interaction with FUS; dbSNP:rs759312530
VAR_077461694C>Yin CMT2P; uncertain significance; dbSNP:rs886041051

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_021051318in dbSNP:rs1539567
Mutagenesis649-664Abolishes interaction with TSG101.
Mutagenesis675Abolishes ubiquitination of TSG101.
Mutagenesis692Abolishes ubiquitination of TSG101.
Natural variantVAR_077460694in CMT2P; abolishes interaction with FUS; dbSNP:rs759312530
Natural variantVAR_077461694in CMT2P; uncertain significance; dbSNP:rs886041051

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 961 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
ChainPRO_00000559231-723UniProtE3 ubiquitin-protein ligase LRSAM1
Modified residue (large scale data)231PRIDEPhosphoserine
Modified residue234UniProtPhosphoserine
Modified residue (large scale data)234PRIDEPhosphoserine
Modified residue (large scale data)243PRIDEPhosphoserine
Modified residue (large scale data)289PRIDEPhosphoserine
Modified residue (large scale data)290PRIDEPhosphoserine
Modified residue (large scale data)494PRIDEPhosphoserine
Modified residue (large scale data)562PRIDEPhosphoserine
Modified residue604UniProtPhosphoserine
Modified residue (large scale data)604PRIDEPhosphoserine

Post-translational modification

Ubiquitination promoted by PHF23 leads to proteasomal degradation.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Highly expressed in adult spinal cord motoneurons as well as in fetal spinal cord and muscle tissue.

Gene expression databases

Organism-specific databases

Interaction

Structure

Family & Domains

Features

Showing features for repeat, coiled coil, region, compositional bias, domain, motif, zinc finger.

TypeIDPosition(s)Description
Repeat30-51LRR 1
Repeat56-77LRR 2
Repeat82-103LRR 3
Repeat105-127LRR 4
Repeat128-149LRR 5
Repeat151-172LRR 6
Coiled coil254-380
Region282-314Disordered
Compositional bias295-314Basic and acidic residues
Coiled coil510-562
Domain569-632SAM
Region642-665Disordered
Motif649-652PTAP motif 1
Motif661-664PTAP motif 2
Zinc finger675-710RING-type

Domain

The coiled coil domains interact with the SB domain of TSG101.
The PTAP motifs mediate the binding to UEV domains.
The LRR domain is necessary and sufficient for localization to bacterial targets.
The RING domain is required for ubiquitination.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

This entry describes 3 isoforms produced by Alternative splicing.

Q6UWE0-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    723
  • Mass (Da)
    83,594
  • Last updated
    2004-07-05 v1
  • Checksum
    4A59461C92467BB1
MPLFFRKRKPSEEARKRLEYQMCLAKEAGADDILDISKCELSEIPFGAFATCKVLQKKVLIVHTNHLTSLLPKSCSLLSLATIKVLDLHDNQLTALPDDLGQLTALQVLNVERNQLMQLPRSIGNLTQLQTLNVKDNKLKELPDTVGELRSLRTLNISGNEIQRLPQMLAHVRTLEMLSLDASAMVYPPREVCGAGTAAILQFLCKESGLEYYPPSQYLLPILEQDGIENSRDSPDGPTDRFSREELEWQNRFSDYEKRKEQKMLEKLEFERRLELGQREHTQLLQQSSSQKDEILQTVKEEQSRLEQGLSEHQRHLNAERQRLQEQLKQTEQNISSRIQKLLQDNQRQKKSSEILKSLENERIRMEQLMSITQEETESLRRRDVASAMQQMLTESCKNRLIQMAYESQRQNLVQQACSSMAEMDERFQQILSWQQMDQNKAISQILQESAMQKAAFEALQVKKDLMHRQIRSQIKLIETELLQLTQLELKRKSLDTESLQEMISEQRWALSSLLQQLLKEKQQREEELREILTELEAKSETRQENYWLIQYQRLLNQKPLSLKLQEEGMERQLVALLEELSAEHYLPIFAHHRLSLDLLSQMSPGDLAKVGVSEAGLQHEILRRVQELLDAARIQPELKPPMGEVVTPTAPQEPPESVRPSAPPAELEVQASECVVCLEREAQMIFLNCGHVCCCQQCCQPLRTCPLCRQDIAQRLRIYHSS

Q6UWE0-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q6UWE0-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 17 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A6Q8PFL5A0A6Q8PFL5_HUMANLRSAM1653
A0A6Q8PFI6A0A6Q8PFI6_HUMANLRSAM1420
A0A6Q8PFL1A0A6Q8PFL1_HUMANLRSAM1254
A0A6Q8PG90A0A6Q8PG90_HUMANLRSAM1173
A0A6Q8PFW1A0A6Q8PFW1_HUMANLRSAM1432
A0A6Q8PFT9A0A6Q8PFT9_HUMANLRSAM1663
A0A6Q8PG02A0A6Q8PG02_HUMANLRSAM1704
A0A6Q8PGH9A0A6Q8PGH9_HUMANLRSAM1149
A0A6Q8PGB2A0A6Q8PGB2_HUMANLRSAM1750
A0A6Q8PGF7A0A6Q8PGF7_HUMANLRSAM1708
A0A6Q8PGZ2A0A6Q8PGZ2_HUMANLRSAM1165
A0A6Q8PGT8A0A6Q8PGT8_HUMANLRSAM1638
A0A6Q8PH70A0A6Q8PH70_HUMANLRSAM1428
A0A6Q8PGW1A0A6Q8PGW1_HUMANLRSAM1690
A0A6Q8PEU7A0A6Q8PEU7_HUMANLRSAM185
A0A6Q8PF55A0A6Q8PF55_HUMANLRSAM1236
A0A6Q8PHH6A0A6Q8PHH6_HUMANLRSAM1407

Features

Showing features for alternative sequence, compositional bias, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0126601-420in isoform 3
Compositional bias295-314Basic and acidic residues
Sequence conflict385in Ref. 2; BAB71119
Sequence conflict402in Ref. 2; BAC03703
Alternative sequenceVSP_012661474-500in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AY358830
EMBL· GenBank· DDBJ
AAQ89189.1
EMBL· GenBank· DDBJ
mRNA
AK056203
EMBL· GenBank· DDBJ
BAB71119.1
EMBL· GenBank· DDBJ
mRNA
AK056305
EMBL· GenBank· DDBJ
BAB71144.1
EMBL· GenBank· DDBJ
mRNA
AK091589
EMBL· GenBank· DDBJ
BAC03703.1
EMBL· GenBank· DDBJ
mRNA
AL445222
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC009239
EMBL· GenBank· DDBJ
AAH09239.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp