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Protein

Lipopolysaccharide-induced tumor necrosis factor-alpha factor

Gene

LITAF

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

Functioni

Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation (PubMed:23166352). 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 (PubMed:23166352). Probably plays a role in regulating protein degradation via its interaction with NEDD4 (PubMed:15776429). May also contribute to the regulation of gene expression in the nucleus (PubMed:10200294, PubMed:15793005). Binds DNA (in vitro) and may play a synergistic role with STAT6 in the nucleus in regulating the expression of various cytokines (PubMed:15793005). May regulate the expression of numerous cytokines, such as TNF, CCL2, CCL5, CXCL1, IL1A and IL10 (PubMed:10200294, PubMed:15793005).1 Publication1 Publication2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi96Zinc2 Publications1
Metal bindingi99Zinc1 Publication1
Metal bindingi148Zinc2 Publications1
Metal bindingi151Zinc1 Publication1

GO - Molecular functioni

  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • signal transducer activity Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • WW domain binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

SIGNORiQ99732

Names & Taxonomyi

Protein namesi
Recommended name:
Lipopolysaccharide-induced tumor necrosis factor-alpha factor1 Publication
Short name:
LPS-induced TNF-alpha factor1 Publication
Alternative name(s):
Small integral membrane protein of lysosome/late endosome1 Publication
p53-induced gene 7 protein1 Publication
Gene namesi
Name:LITAF
Synonyms:PIG72 Publications, SIMPLE1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000189067.12
HGNCiHGNC:16841 LITAF
MIMi603795 gene
neXtProtiNX_Q99732

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

Involvement in diseasei

Charcot-Marie-Tooth disease 1C (CMT1C)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA dominant demyelinating 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). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet.
See also OMIM:601098
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02401549T → M in CMT1C. 1 PublicationCorresponds to variant dbSNP:rs141862602Ensembl.1
Natural variantiVAR_024017112G → S in CMT1C; does not abolish interaction with NEDD4 and TSG101. 5 PublicationsCorresponds to variant dbSNP:rs104894519Ensembl.1
Natural variantiVAR_024018115T → N in CMT1C; does not abolish interaction with NEDD4 and TSG101. 2 PublicationsCorresponds to variant dbSNP:rs104894520Ensembl.1
Natural variantiVAR_024019116W → G in CMT1C; decreases protein stability and association with early endosome membranes; impaired function in targeting endocytosed proteins for lysosomal degradation; does not abolish interaction with NEDD4 and TSG101. 4 PublicationsCorresponds to variant dbSNP:rs104894521Ensembl.1
Natural variantiVAR_024020122L → V in CMT1C. 1 PublicationCorresponds to variant dbSNP:rs104894522Ensembl.1
Defects in LITAF may be involved in extramammary Paget disease (EMPD) carcinogenesis. EMPD is a cancerous disease representing about 8% of all malignant skin cancers; it usually appears in the anogenital area and can be fatal by metastasizing to internal organs when left untreated for a long time. The clinical features are usually those of eczematous eruptions with weeping and crust formation.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi17 – 20PSAP → ASAA: Impaired function in targeting endocytosed proteins for lysosomal degradation. 1 Publication4
Mutagenesisi17 – 19PSA → AGG: Abolishes interaction with TSG101. 1 Publication3
Mutagenesisi23Y → A: Abolishes interaction with NEDD4. 1 Publication1
Mutagenesisi23Y → A: Abolishes interaction with WWOX. Abolishes interaction with NEDD4. Abolishes interaction with NEDD4 and impairs location at endosomes; when associated with A-61. 2 Publications1
Mutagenesisi61Y → A: No effect on interaction with WWOX. No effect on interaction with NEDD4. Abolishes interaction with NEDD4 and impairs location at endosomes; when associated with A-23. 2 Publications1
Mutagenesisi96C → A: Abolishes association with cytoplasmic vesicle membranes. 1 Publication1
Mutagenesisi135P → T: Decreases protein stability and association with early endosome membranes. Impaired function in targeting endocytosed proteins for lysosomal degradation. 2 Publications1
Mutagenesisi144V → M: No effect on location at endosomes, but impairs protein stability. 1 Publication1
Mutagenesisi148C → A: Abolishes association with cytoplasmic vesicle membranes. 1 Publication1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi9516
GeneReviewsiLITAF
MalaCardsiLITAF
MIMi601098 phenotype
OpenTargetsiENSG00000189067
Orphaneti101083 Charcot-Marie-Tooth disease type 1C
PharmGKBiPA134879224

Polymorphism and mutation databases

BioMutaiLITAF
DMDMi83304387

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000844401 – 161Lipopolysaccharide-induced tumor necrosis factor-alpha factorAdd BLAST161

Post-translational modificationi

Phosphorylated on tyrosine residues in response to EGF.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ99732
PeptideAtlasiQ99732
PRIDEiQ99732

PTM databases

iPTMnetiQ99732
PhosphoSitePlusiQ99732

Expressioni

Tissue specificityi

Ubiquitously and abundantly expressed. Expressed predominantly in the placenta, peripheral blood leukocytes, lymph nodes and spleen.2 Publications

Inductioni

Up-regulated by bacterial lipopolysaccharide (LPS) (at protein level) (PubMed:15793005). By bacterial lipopolysaccharide (LPS) and by p53/TP53 (PubMed:9305847, PubMed:10200294). In monocytes by the Bacillus Calmette-Guerin (BCG) (PubMed:11274176).4 Publications

Gene expression databases

BgeeiENSG00000189067
CleanExiHS_LITAF
ExpressionAtlasiQ99732 baseline and differential
GenevisibleiQ99732 HS

Organism-specific databases

HPAiHPA006960

Interactioni

Subunit structurei

Monomer (PubMed:27927196). Interacts with NEDD4 (PubMed:16118794, PubMed:27927196). Interacts (via PSAP motif) with TSG101, a component of the ESCRT-I complex (endosomal sorting complex required for transport I) (PubMed:16118794). Interacts with WWOX (PubMed:15064722). Interacts with STAM, a component of the ESCRT-0 complex; the interaction is direct (PubMed:23166352). Identified in a complex with STAM and HGS; within this complex, interacts directly with STAM, but not with HGS (PubMed:23166352). Interacts with STAT6 (PubMed:15793005).1 Publication4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • WW domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114893, 41 interactors
IntActiQ99732, 34 interactors
STRINGi9606.ENSP00000340118

Structurei

3D structure databases

ProteinModelPortaliQ99732
ModBaseiSearch...
MobiDBiSearch...

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 helix1 PublicationAdd BLAST24

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi17 – 20PSAP motif; important for interaction with TSG1012 Publications4
Motifi20 – 23PPxY motif3 Publications4

Domaini

The PPxY motif mediates interaction with WWOX and NEDD4.2 Publications
The LITAF domain is stabilized by a bound zinc ion (PubMed:27927196, PubMed:27582497). The LITAF domain contains an amphiphatic helix that mediates interaction with lipid membranes (PubMed:23166352, PubMed:27927196, PubMed:27582497). It interacts specifically with phosphatidylethanolamine lipid headgroups, but not with phosphoglycerol, phosphocholine, phosphoserine or inositolhexakisphosphate (PubMed:27927196).3 Publications

Sequence similaritiesi

Belongs to the CDIP1/LITAF family.Curated

Phylogenomic databases

eggNOGiENOG410IVVU Eukaryota
ENOG41122PJ LUCA
GeneTreeiENSGT00540000071542
HOGENOMiHOG000039585
HOVERGENiHBG006272
InParanoidiQ99732
KOiK19363
OMAiTMAINSH
OrthoDBiEOG091G0XNM
PhylomeDBiQ99732
TreeFamiTF313294

Family and domain databases

InterProiView protein in InterPro
IPR006629 LITAF
IPR037519 LITAF_fam
PANTHERiPTHR23292 PTHR23292, 1 hit
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

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q99732-1) [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
MSVPGPYQAA TGPSSAPSAP PSYEETVAVN SYYPTPPAPM PGPTTGLVTG
60 70 80 90 100
PDGKGMNPPS YYTQPAPIPN NNPITVQTVY VQHPITFLDR PIQMCCPSCN
110 120 130 140 150
KMIVSQLSYN AGALTWLSCG SLCLLGCIAG CCFIPFCVDA LQDVDHYCPN
160
CRALLGTYKR L
Length:161
Mass (Da):17,107
Last modified:December 6, 2005 - v2
Checksum:i08D15BF1FDCA16F0
GO
Isoform 2 (identifier: Q99732-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     127-161: CIAGCCFIPFCVDALQDVDHYCPNCRALLGTYKRL → VHSGLLLHPL...TPEIAAWSRA

Note: May be due to a frameshift that creates an unconventional splicing site. Data inferred from this isoform must be interpreted with caution.
Show »
Length:228
Mass (Da):23,903
Checksum:i2672B55AD96FC4B5
GO
Isoform 3 (identifier: Q99732-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     127-161: CIAGCCFIPFCVDALQDVDHYCPNCRALLGTYKRL → QECSGTIVALRSFDLLGSCNPPSSAS

Note: No experimental confirmation available.
Show »
Length:152
Mass (Da):15,824
Checksum:iE2270BD322D63344
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02401423Y → H in one EMPD primary tumor; somatic mutation. 1 Publication1
Natural variantiVAR_02401549T → M in CMT1C. 1 PublicationCorresponds to variant dbSNP:rs141862602Ensembl.1
Natural variantiVAR_02401692I → V2 PublicationsCorresponds to variant dbSNP:rs4280262Ensembl.1
Natural variantiVAR_024017112G → S in CMT1C; does not abolish interaction with NEDD4 and TSG101. 5 PublicationsCorresponds to variant dbSNP:rs104894519Ensembl.1
Natural variantiVAR_024018115T → N in CMT1C; does not abolish interaction with NEDD4 and TSG101. 2 PublicationsCorresponds to variant dbSNP:rs104894520Ensembl.1
Natural variantiVAR_024019116W → G in CMT1C; decreases protein stability and association with early endosome membranes; impaired function in targeting endocytosed proteins for lysosomal degradation; does not abolish interaction with NEDD4 and TSG101. 4 PublicationsCorresponds to variant dbSNP:rs104894521Ensembl.1
Natural variantiVAR_024020122L → V in CMT1C. 1 PublicationCorresponds to variant dbSNP:rs104894522Ensembl.1
Isoform 2 (identifier: Q99732-2)
Natural varianti174A → S Found as a somatic mutation in a EMPD primary tumor. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_016461127 – 161CIAGC…TYKRL → VHSGLLLHPLLRGCPAGRGP LLSQLQSSPGHLQAFVGLSQ TWREPGAAGSPFHLSSSFTP GGGSALVVSPLQGAHLHVFF WGEYVAKLTNLQTPEIAAWS RA in isoform 2. 2 PublicationsAdd BLAST35
Alternative sequenceiVSP_045701127 – 161CIAGC…TYKRL → QECSGTIVALRSFDLLGSCN PPSSAS in isoform 3. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF010312 mRNA Translation: AAC39530.1
U77396 mRNA Translation: AAB36550.1
AB034747 mRNA Translation: BAB32547.1
AK095955 mRNA No translation available.
BX537543 mRNA Translation: CAD97778.1
AC007616 Genomic DNA No translation available.
AC099489 Genomic DNA No translation available.
CH471112 Genomic DNA Translation: EAW85150.1
CH471112 Genomic DNA Translation: EAW85151.1
CH471112 Genomic DNA Translation: EAW85152.1
CH471112 Genomic DNA Translation: EAW85153.1
BC000053 mRNA Translation: AAH00053.1
BC008309 mRNA Translation: AAH08309.1
BC016491 mRNA Translation: AAH16491.1
BC039840 mRNA Translation: AAH39840.1
BC046154 mRNA Translation: AAH46154.1
BC096063 mRNA Translation: AAH96063.1
BC096065 mRNA Translation: AAH96065.1
BC096066 mRNA Translation: AAH96066.1
BC101401 mRNA Translation: AAI01402.1
BC101402 mRNA Translation: AAI01403.1
BC101969 mRNA Translation: AAI01970.1
CCDSiCCDS32386.1 [Q99732-1]
CCDS45411.1 [Q99732-3]
RefSeqiNP_001129944.1, NM_001136472.1 [Q99732-1]
NP_001129945.1, NM_001136473.1 [Q99732-3]
NP_004853.2, NM_004862.3 [Q99732-1]
XP_006721045.1, XM_006720982.2 [Q99732-1]
XP_006721046.1, XM_006720983.3 [Q99732-1]
XP_006721047.1, XM_006720984.3 [Q99732-1]
XP_006721048.1, XM_006720985.3 [Q99732-1]
XP_016879385.1, XM_017023896.1 [Q99732-1]
UniGeneiHs.459940

Genome annotation databases

EnsembliENST00000339430; ENSP00000340118; ENSG00000189067 [Q99732-1]
ENST00000381810; ENSP00000371231; ENSG00000189067 [Q99732-2]
ENST00000413364; ENSP00000397958; ENSG00000189067 [Q99732-3]
ENST00000570904; ENSP00000459138; ENSG00000189067 [Q99732-1]
ENST00000571688; ENSP00000459533; ENSG00000189067 [Q99732-1]
ENST00000574763; ENSP00000461813; ENSG00000189067 [Q99732-1]
ENST00000576036; ENSP00000461667; ENSG00000189067 [Q99732-1]
ENST00000620789; ENSP00000481589; ENSG00000189067 [Q99732-3]
ENST00000622633; ENSP00000483114; ENSG00000189067 [Q99732-1]
GeneIDi9516
KEGGihsa:9516
UCSCiuc002daz.4 human [Q99732-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLITAF_HUMAN
AccessioniPrimary (citable) accession number: Q99732
Secondary accession number(s): D3DUG1
, G5E9K0, Q05DW0, Q9C0L6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: December 6, 2005
Last modified: March 28, 2018
This is version 163 of the entry and version 2 of the sequence. See 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
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Main funding by: National Institutes of Health