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Protein

Lipopolysaccharide-induced tumor necrosis factor-alpha factor

Gene

LITAF

Organism
Homo sapiens (Human)
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 (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

  • signal transducer activity Source: UniProtKB
  • WW domain binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

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

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

HGNCiHGNC:16841. LITAF.

Subcellular locationi

GO - Cellular componenti

  • cytoplasmic side of early endosome membrane Source: UniProtKB
  • cytoplasmic side of late endosome membrane Source: UniProtKB
  • cytoplasmic side of lysosomal membrane Source: UniProtKB
  • cytoplasmic side of plasma membrane Source: UniProtKB
  • cytosol Source: HPA
  • Golgi apparatus Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • lysosomal membrane Source: MGI
  • nucleoplasm Source: HPA
  • plasma membrane Source: UniProtKB

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 1C (CMT1C)6 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. 4 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.
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

EPDiQ99732.
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. 40 interactors.
IntActiQ99732. 34 interactors.
MINTiMINT-1391850.
STRINGi9606.ENSP00000340118.

Structurei

3D structure databases

ProteinModelPortaliQ99732.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini90 – 159LITAFCuratedAdd BLAST70

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 – 23WW-binding3 Publications4

Domaini

The WW-binding 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.
OMAiVYVQPGL.
OrthoDBiEOG091G0XNM.
PhylomeDBiQ99732.
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.

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. 4 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

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.

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: July 5, 2017
This is version 155 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

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. SIMILARITY comments
    Index of protein domains and families