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Protein

E3 ubiquitin-protein ligase LRSAM1

Gene

LRSAM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.2 Publications
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri675 – 710RING-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • negative regulation of endocytosis Source: UniProtKB
  • positive regulation of autophagosome assembly Source: GO_Central
  • positive regulation of xenophagy Source: GO_Central
  • protein autoubiquitination Source: UniProtKB
  • protein catabolic process Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
  • ubiquitin-dependent endocytosis Source: UniProtKB
  • viral budding Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Autophagy, Protein transport, Transport, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase LRSAM1Curated (EC:6.3.2.-2 Publications)
Alternative name(s):
Leucine-rich repeat and sterile alpha motif-containing protein 11 Publication
Tsg101-associated ligase1 Publication
Short name:
hTAL1 Publication
Gene namesi
Name:LRSAM11 Publication
Synonyms:TAL1 Publication
ORF Names:UNQ6496/PRO21356
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:25135. LRSAM1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 2P (CMT2P)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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. Nerve conduction velocities are normal or slightly reduced.
See also OMIM:614436

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi649 – 664Missing : Abolishes interaction with TSG101. 1 PublicationAdd BLAST16
Mutagenesisi675C → A: Abolishes ubiquitination of TSG101. 1 Publication1
Mutagenesisi692H → A: Abolishes ubiquitination of TSG101. 1 Publication1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi90678.
MalaCardsiLRSAM1.
MIMi614436. phenotype.
OpenTargetsiENSG00000148356.
Orphaneti300319. Autosomal dominant Charcot-Marie-Tooth disease type 2P.
PharmGKBiPA134890010.

Polymorphism and mutation databases

BioMutaiLRSAM1.
DMDMi62511890.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000559231 – 723E3 ubiquitin-protein ligase LRSAM1Add BLAST723

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei234PhosphoserineCombined sources1
Modified residuei604PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitination promoted by PHF23 leads to proteasomal degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ6UWE0.
MaxQBiQ6UWE0.
PaxDbiQ6UWE0.
PeptideAtlasiQ6UWE0.
PRIDEiQ6UWE0.

PTM databases

iPTMnetiQ6UWE0.
PhosphoSitePlusiQ6UWE0.

Expressioni

Tissue specificityi

Highly expressed in adult spinal cord motoneurons as well as in fetal spinal cord and muscle tissue.1 Publication

Gene expression databases

BgeeiENSG00000148356.
CleanExiHS_LRSAM1.
ExpressionAtlasiQ6UWE0. baseline and differential.
GenevisibleiQ6UWE0. HS.

Organism-specific databases

HPAiCAB037304.
HPA021403.
HPA021844.

Interactioni

Subunit structurei

Interacts with TSG101 (PubMed:17556548). Interacts with PHF23 (PubMed:25484098).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF1P542742EBI-720984,EBI-710997
TSG101Q998169EBI-720984,EBI-346882
UBE2NP610883EBI-720984,EBI-1052908

Protein-protein interaction databases

BioGridi124754. 54 interactors.
IntActiQ6UWE0. 39 interactors.
MINTiMINT-1377718.
STRINGi9606.ENSP00000300417.

Structurei

3D structure databases

ProteinModelPortaliQ6UWE0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati30 – 51LRR 1Add BLAST22
Repeati56 – 77LRR 2Add BLAST22
Repeati82 – 103LRR 3Add BLAST22
Repeati105 – 127LRR 4Add BLAST23
Repeati128 – 149LRR 5Add BLAST22
Repeati151 – 172LRR 6Add BLAST22
Domaini569 – 632SAMPROSITE-ProRule annotationAdd BLAST64

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili254 – 380Sequence analysisAdd BLAST127
Coiled coili510 – 562Sequence analysisAdd BLAST53

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi649 – 652PTAP motif 14
Motifi661 – 664PTAP motif 24

Domaini

The coiled coil domains interact with the SB domain of TSG101.1 Publication
The PTAP motifs mediate the binding to UEV domains.1 Publication
The LRR domain is necessary and sufficient for localization to bacterial targets.1 Publication
The RING domain is required for ubiquitination.1 Publication

Sequence similaritiesi

Contains 6 LRR (leucine-rich) repeats.Curated
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri675 – 710RING-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Coiled coil, Leucine-rich repeat, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00840000129676.
HOGENOMiHOG000231972.
HOVERGENiHBG052363.
InParanoidiQ6UWE0.
KOiK10641.
OMAiFGAFATC.
OrthoDBiEOG091G02SW.
PhylomeDBiQ6UWE0.
TreeFamiTF329645.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
3.30.40.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF13855. LRR_8. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 4 hits.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 4 hits.
PS50105. SAM_DOMAIN. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6UWE0-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPLFFRKRKP SEEARKRLEY QMCLAKEAGA DDILDISKCE LSEIPFGAFA
60 70 80 90 100
TCKVLQKKVL IVHTNHLTSL LPKSCSLLSL ATIKVLDLHD NQLTALPDDL
110 120 130 140 150
GQLTALQVLN VERNQLMQLP RSIGNLTQLQ TLNVKDNKLK ELPDTVGELR
160 170 180 190 200
SLRTLNISGN EIQRLPQMLA HVRTLEMLSL DASAMVYPPR EVCGAGTAAI
210 220 230 240 250
LQFLCKESGL EYYPPSQYLL PILEQDGIEN SRDSPDGPTD RFSREELEWQ
260 270 280 290 300
NRFSDYEKRK EQKMLEKLEF ERRLELGQRE HTQLLQQSSS QKDEILQTVK
310 320 330 340 350
EEQSRLEQGL SEHQRHLNAE RQRLQEQLKQ TEQNISSRIQ KLLQDNQRQK
360 370 380 390 400
KSSEILKSLE NERIRMEQLM SITQEETESL RRRDVASAMQ QMLTESCKNR
410 420 430 440 450
LIQMAYESQR QNLVQQACSS MAEMDERFQQ ILSWQQMDQN KAISQILQES
460 470 480 490 500
AMQKAAFEAL QVKKDLMHRQ IRSQIKLIET ELLQLTQLEL KRKSLDTESL
510 520 530 540 550
QEMISEQRWA LSSLLQQLLK EKQQREEELR EILTELEAKS ETRQENYWLI
560 570 580 590 600
QYQRLLNQKP LSLKLQEEGM ERQLVALLEE LSAEHYLPIF AHHRLSLDLL
610 620 630 640 650
SQMSPGDLAK VGVSEAGLQH EILRRVQELL DAARIQPELK PPMGEVVTPT
660 670 680 690 700
APQEPPESVR PSAPPAELEV QASECVVCLE REAQMIFLNC GHVCCCQQCC
710 720
QPLRTCPLCR QDIAQRLRIY HSS
Length:723
Mass (Da):83,594
Last modified:July 5, 2004 - v1
Checksum:i4A59461C92467BB1
GO
Isoform 2 (identifier: Q6UWE0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     474-500: Missing.

Show »
Length:696
Mass (Da):80,428
Checksum:iFA5BF4FF6584DBA0
GO
Isoform 3 (identifier: Q6UWE0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-420: Missing.

Note: No experimental confirmation available.
Show »
Length:303
Mass (Da):35,069
Checksum:iA92853EEC27F0B12
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti385V → F in BAB71119 (PubMed:14702039).Curated1
Sequence conflicti402I → V in BAC03703 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021051318N → D.1 PublicationCorresponds to variant rs1539567dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0126601 – 420Missing in isoform 3. 1 PublicationAdd BLAST420
Alternative sequenceiVSP_012661474 – 500Missing in isoform 2. 1 PublicationAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358830 mRNA. Translation: AAQ89189.1.
AK056203 mRNA. Translation: BAB71119.1.
AK056305 mRNA. Translation: BAB71144.1.
AK091589 mRNA. Translation: BAC03703.1.
AL445222 Genomic DNA. Translation: CAH72930.1.
AL445222 Genomic DNA. Translation: CAH72931.1.
BC009239 mRNA. Translation: AAH09239.1.
CCDSiCCDS55347.1. [Q6UWE0-2]
CCDS6873.1. [Q6UWE0-1]
RefSeqiNP_001005373.1. NM_001005373.3. [Q6UWE0-1]
NP_001005374.1. NM_001005374.3. [Q6UWE0-1]
NP_001177652.1. NM_001190723.2. [Q6UWE0-2]
NP_612370.3. NM_138361.5. [Q6UWE0-1]
XP_016870772.1. XM_017015283.1. [Q6UWE0-1]
UniGeneiHs.495188.

Genome annotation databases

EnsembliENST00000300417; ENSP00000300417; ENSG00000148356. [Q6UWE0-1]
ENST00000323301; ENSP00000322937; ENSG00000148356. [Q6UWE0-1]
ENST00000373322; ENSP00000362419; ENSG00000148356. [Q6UWE0-1]
ENST00000373324; ENSP00000362421; ENSG00000148356. [Q6UWE0-2]
GeneIDi90678.
KEGGihsa:90678.
UCSCiuc004brb.2. human. [Q6UWE0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358830 mRNA. Translation: AAQ89189.1.
AK056203 mRNA. Translation: BAB71119.1.
AK056305 mRNA. Translation: BAB71144.1.
AK091589 mRNA. Translation: BAC03703.1.
AL445222 Genomic DNA. Translation: CAH72930.1.
AL445222 Genomic DNA. Translation: CAH72931.1.
BC009239 mRNA. Translation: AAH09239.1.
CCDSiCCDS55347.1. [Q6UWE0-2]
CCDS6873.1. [Q6UWE0-1]
RefSeqiNP_001005373.1. NM_001005373.3. [Q6UWE0-1]
NP_001005374.1. NM_001005374.3. [Q6UWE0-1]
NP_001177652.1. NM_001190723.2. [Q6UWE0-2]
NP_612370.3. NM_138361.5. [Q6UWE0-1]
XP_016870772.1. XM_017015283.1. [Q6UWE0-1]
UniGeneiHs.495188.

3D structure databases

ProteinModelPortaliQ6UWE0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124754. 54 interactors.
IntActiQ6UWE0. 39 interactors.
MINTiMINT-1377718.
STRINGi9606.ENSP00000300417.

PTM databases

iPTMnetiQ6UWE0.
PhosphoSitePlusiQ6UWE0.

Polymorphism and mutation databases

BioMutaiLRSAM1.
DMDMi62511890.

Proteomic databases

EPDiQ6UWE0.
MaxQBiQ6UWE0.
PaxDbiQ6UWE0.
PeptideAtlasiQ6UWE0.
PRIDEiQ6UWE0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000300417; ENSP00000300417; ENSG00000148356. [Q6UWE0-1]
ENST00000323301; ENSP00000322937; ENSG00000148356. [Q6UWE0-1]
ENST00000373322; ENSP00000362419; ENSG00000148356. [Q6UWE0-1]
ENST00000373324; ENSP00000362421; ENSG00000148356. [Q6UWE0-2]
GeneIDi90678.
KEGGihsa:90678.
UCSCiuc004brb.2. human. [Q6UWE0-1]

Organism-specific databases

CTDi90678.
DisGeNETi90678.
GeneCardsiLRSAM1.
GeneReviewsiLRSAM1.
HGNCiHGNC:25135. LRSAM1.
HPAiCAB037304.
HPA021403.
HPA021844.
MalaCardsiLRSAM1.
MIMi610933. gene.
614436. phenotype.
neXtProtiNX_Q6UWE0.
OpenTargetsiENSG00000148356.
Orphaneti300319. Autosomal dominant Charcot-Marie-Tooth disease type 2P.
PharmGKBiPA134890010.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00840000129676.
HOGENOMiHOG000231972.
HOVERGENiHBG052363.
InParanoidiQ6UWE0.
KOiK10641.
OMAiFGAFATC.
OrthoDBiEOG091G02SW.
PhylomeDBiQ6UWE0.
TreeFamiTF329645.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

ChiTaRSiLRSAM1. human.
GeneWikiiLRSAM1.
GenomeRNAii90678.
PROiQ6UWE0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000148356.
CleanExiHS_LRSAM1.
ExpressionAtlasiQ6UWE0. baseline and differential.
GenevisibleiQ6UWE0. HS.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
3.30.40.10. 1 hit.
3.80.10.10. 1 hit.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF13855. LRR_8. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 4 hits.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 4 hits.
PS50105. SAM_DOMAIN. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLRSM1_HUMAN
AccessioniPrimary (citable) accession number: Q6UWE0
Secondary accession number(s): Q5VVV0
, Q8NB40, Q96GT5, Q96MX5, Q96MZ7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 2005
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 135 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.