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Protein

Lipopolysaccharide-induced tumor necrosis factor-alpha factor homolog

Gene

Litaf

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation. Plays a role in targeting endocytosed EGFR and ERGG3 for lysosomal degradation, and thereby helps downregulate downstream signaling cascades (PubMed:23166352). Helps recruit the ESCRT complex components TSG101, HGS and STAM to cytoplasmic membranes. Probably plays a role in regulating protein degradation via its interaction with NEDD4 (By similarity). May also contribute to the regulation of gene expression in the nucleus. Binds DNA (in vitro) and may play a synergistic role with STAT6 in the nucleus in regulating the expression of various cytokines (PubMed:15793005, PubMed:21980379). May regulate the expression of numerous cytokines, such as TNF, CCL2, CCL5, CXCL1, IL1A and IL10 (PubMed:12355436, PubMed:15025820, PubMed:16954198, PubMed:21980379, PubMed:22160695).By similarity6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi96ZincBy similarity1
Metal bindingi99ZincBy similarity1
Metal bindingi148ZincBy similarity1
Metal bindingi151ZincBy similarity1

GO - Molecular functioni

GO - Biological processi

  • aging Source: Ensembl
  • cellular response to lipopolysaccharide Source: MGI
  • negative regulation of NF-kappaB import into nucleus Source: MGI
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • regulation of cytokine production Source: MGI
  • response to lipopolysaccharide Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionDNA-binding
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Lipopolysaccharide-induced tumor necrosis factor-alpha factor homolog
Short name:
LPS-induced TNF-alpha factor homolog
Alternative name(s):
Estrogen-enhanced transcript protein1 Publication
Short name:
mEET1 Publication
LITAF-like protein
NEDD4 WW domain-binding protein 3
Gene namesi
Name:Litaf
Synonyms:N4wbp3, Tbx1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 16

Organism-specific databases

MGIiMGI:1929512. Litaf.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Golgi apparatus, Lysosome, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice are born at the expected Mendelian rate and are fertile. Mutant mice display altered responses to nerve crush injury, with higher numbers of macrophages in injured nerves five days after nerve crush injury, but at later time points macrophage numbers in injured nerves are normal. Bone marrow-derived macrophages from mutant mice display increased migration in response to CCL3, but not in the absence of CCL3 (PubMed:22729949). Mutant mice show dramatically increased survival in response to a dose of lipopolysaccharide (LPS) that causes rapid death of 40% of wild-type mice (PubMed:22160695).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23Y → A: Abolishes interaction with NEDD4. 1 Publication1
Mutagenesisi61Y → A: No effect on interaction with NEDD4. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000844411 – 161Lipopolysaccharide-induced tumor necrosis factor-alpha factor homologAdd BLAST161

Post-translational modificationi

Phosphorylated on tyrosine residues in response to EGF.By similarity

Proteomic databases

PaxDbiQ9JLJ0.
PRIDEiQ9JLJ0.

PTM databases

iPTMnetiQ9JLJ0.
PhosphoSitePlusiQ9JLJ0.

Expressioni

Tissue specificityi

Detected in brain, heart, lung, liver, spleen and bone marrow (PubMed:22160695). Detected in myelinating Schwann cells in sciatic nerve and in bone marrow-derived macrophages (at protein level) (PubMed:22729949). Widely expressed. Highly expressed in liver.4 Publications

Developmental stagei

Expression in sciatic nerve is low in neonates, culminates seven days after birth and decreases rapidly thereafter (at protein level) (PubMed:22729949). Strong expression is detected at E.7 and drops at E11.2 Publications

Inductioni

Up-regulated in macrophages exposed to lipopolysaccharide (LPS) (at protein level) (PubMed:15793005). By estrogen and lipopolysaccharides (LPS).3 Publications

Gene expression databases

BgeeiENSMUSG00000022500.
CleanExiMM_LITAF.
MM_TBX1.
ExpressionAtlasiQ9JLJ0. baseline and differential.
GenevisibleiQ9JLJ0. MM.

Interactioni

Subunit structurei

Monomer. Interacts with NEDD4 (PubMed:11042109). Interacts (via PSAP motif) with TSG101, a component of the ESCRT-I complex (endosomal sorting complex required for transport I). Interacts with WWOX. Interacts with STAM, a component of the ESCRT-0 complex; the interaction is direct. Identified in a complex with STAM and HGS; within this complex, interacts directly with STAM, but not with HGS. Interacts with STAT6 (PubMed:15793005).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Nedd4P469355EBI-643664,EBI-773516

GO - Molecular functioni

Protein-protein interaction databases

BioGridi208144. 2 interactors.
IntActiQ9JLJ0. 2 interactors.
MINTiMINT-147796.
STRINGi10090.ENSMUSP00000023143.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini76 – 160LITAFPROSITE-ProRule annotationAdd BLAST85

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni111 – 134Membrane-binding amphipathic helixCuratedAdd BLAST24

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi20 – 23PPxY motif4

Domaini

The PPxY motif mediates interaction with WWOX and NEDD4.By similarity
The LITAF domain is stabilized by a bound zinc ion. The LITAF domain contains an amphiphatic helix that mediates interaction with lipid membranes. It interacts specifically with phosphatidylethanolamine lipid headgroups, but not with phosphoglycerol, phosphocholine, phosphoserine or inositolhexakisphosphate.By similarity

Sequence similaritiesi

Belongs to the CDIP1/LITAF family.Curated

Phylogenomic databases

eggNOGiENOG410IVVU. Eukaryota.
ENOG41122PJ. LUCA.
GeneTreeiENSGT00540000071542.
HOGENOMiHOG000039585.
HOVERGENiHBG006272.
InParanoidiQ9JLJ0.
KOiK19363.
OMAiHCHAEID.
OrthoDBiEOG091G0XNM.
PhylomeDBiQ9JLJ0.
TreeFamiTF313294.

Family and domain databases

InterProiView protein in InterPro
IPR006629. LITAF.
PfamiView protein in Pfam
PF10601. zf-LITAF-like. 1 hit.
SMARTiView protein in SMART
SM00714. LITAF. 1 hit.
PROSITEiView protein in PROSITE
PS51837. LITAF. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9JLJ0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAPGPYQAA AGPSVVPTAP PTYEETVGVN SYYPTPPAPM PGPATGLITG
60 70 80 90 100
PDGKGMNPPS YYTQPVPVPN ANAIAVQTVY VQQPVSFYDR PVQMCCPSCS
110 120 130 140 150
KMIVTQLSYN AGALTWLSCG SLCLLGCVAG CCFIPFCVDA LQDVDHYCPN
160
CKALLGTYKR L
Length:161
Mass (Da):16,946
Last modified:October 1, 2000 - v1
Checksum:i7397F79C5AD0CD79
GO

Sequence cautioni

The sequence AAG44246 differs from that shown. Reason: Erroneous initiation.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF171100 mRNA. Translation: AAF27312.1.
AF230522 mRNA. Translation: AAO49168.1.
AK018578 mRNA. Translation: BAB31289.1.
AK076162 mRNA. Translation: BAC36228.1.
AK151053 mRNA. Translation: BAE30070.1.
AK159533 mRNA. Translation: BAE35161.1.
BC018559 mRNA. Translation: AAH18559.1.
AF220207 mRNA. Translation: AAG44246.1. Different initiation.
CCDSiCCDS27958.1.
RefSeqiNP_064364.1. NM_019980.2.
XP_006522490.1. XM_006522427.1.
UniGeneiMm.294753.

Genome annotation databases

EnsembliENSMUST00000023143; ENSMUSP00000023143; ENSMUSG00000022500.
ENSMUST00000117360; ENSMUSP00000112667; ENSMUSG00000022500.
GeneIDi56722.
KEGGimmu:56722.
UCSCiuc007yen.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiLITAF_MOUSE
AccessioniPrimary (citable) accession number: Q9JLJ0
Secondary accession number(s): Q9EQI0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: October 1, 2000
Last modified: November 22, 2017
This is version 116 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families