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Reviewed, UniProtKB/Swiss-Prot Q99732 (LITAF_HUMAN)

Last modified June 16, 2009. Version 75. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Lipopolysaccharide-induced tumor necrosis factor-alpha factor
      Short name=LPS-induced TNF-alpha factor
Alternative name(s):
    p53-induced gene 7 protein
    Small integral membrane protein of lysosome/late endosome
Gene names
Name: LITAF
Synonyms: PIG7, SIMPLE
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length161 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Probable role in regulating transcription of specific genes. May regulate through NFKB1 the expression of the CCL2/MCP-1 chemokine. May play a role in tumor necrosis factor alpha (TNF-alpha) gene expression.

Subunit structure

Interacts with NEDD4 By similarity. Interacts with WWOX. Isoform 2 may interact with STAT6.

Subcellular location

Lysosome membrane; Peripheral membrane protein; Cytoplasmic side. Note: Associated with membranes of lysosomes. Ref.3

Tissue specificity

Ubiquitously and abundantly expressed. Expressed predominantly in the placenta, peripheral blood leukocytes, lymph nodes and spleen. Ref.3 Ref.2

Induction

By lipopolysaccharides (LPS) or TP53/p53. In monocytes by the Bacillus Calmette-Guerin (BCG). Ref.3 Ref.2 Ref.1

Domain

The WW-binding motif mediates interaction with WWOX and, probably NEDD4. Ref.6

Involvement in disease

Defects in LITAF are the cause of Charcot-Marie-Tooth disease type 1C (CMT1C) [MIM:601098]. CMT1C is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT1 group 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. Ref.8 Ref.10 Ref.11

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. Ref.9

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q99732-1)

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.
Isoform 2 (identifier: Q99732-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Natural variant1741A → S Found as a somatic mutation in a EMPD primary tumor.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 161161Lipopolysaccharide-induced tumor necrosis factor-alpha factor
PRO_0000084440

Regions

Motif20 – 234WW-binding

Natural variations

Alternative sequence127 – 16135CIAGC…TYKRL → VHSGLLLHPLLRGCPAGRGP LLSQLQSSPGHLQAFVGLSQ TWREPGAAGSPFHLSSSFTP GGGSALVVSPLQGAHLHVFF WGEYVAKLTNLQTPEIAAWS RA in isoform 2.
VSP_016461
Natural variant231Y → H in one EMPD primary tumor; somatic mutation. Ref.9
VAR_024014
Natural variant491T → M in CMT1C. Ref.11
VAR_024015
Natural variant921I → V: dbSNP rs4280262. Ref.10 Ref.11
VAR_024016
Natural variant1121G → S in CMT1C. Ref.8 Ref.10 Ref.11
VAR_024017
Natural variant1151T → N in CMT1C. Ref.8
VAR_024018
Natural variant1161W → G in CMT1C. Ref.8
VAR_024019
Natural variant1221L → V in CMT1C. Ref.11
VAR_024020

Experimental info

Mutagenesis231Y → A: Abolishes interactions with WWOX. Ref.6
Mutagenesis611Y → A: No effect on interaction with WWOX. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 6, 2005. Version 2.
Checksum: 08D15BF1FDCA16F0

FASTA16117,107
        10         20         30         40         50         60 
MSVPGPYQAA TGPSSAPSAP PSYEETVAVN SYYPTPPAPM PGPTTGLVTG PDGKGMNPPS 

        70         80         90        100        110        120 
YYTQPAPIPN NNPITVQTVY VQHPITFLDR PIQMCCPSCN KMIVSQLSYN AGALTWLSCG 

       130        140        150        160 
SLCLLGCIAG CCFIPFCVDA LQDVDHYCPN CRALLGTYKR L 

« Hide

Isoform 2.

Checksum: 2672B55AD96FC4B5
Show »

FASTA22823,903

References

« Hide 'large scale' references
[1]"A model for p53-induced apoptosis."
Polyak K., Xia Y., Zweier J.L., Kinzler K.W., Vogelstein B.
Nature 389:300-306(1997) [PubMed: 9305847] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION BY TP53.
Tissue: Colon cancer.
[2]"A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha gene expression: molecular cloning, sequencing, characterization, and chromosomal assignment."
Myokai F., Takashiba S., Lebo R., Amar S.
Proc. Natl. Acad. Sci. U.S.A. 96:4518-4523(1999) [PubMed: 10200294] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INDUCTION, TISSUE SPECIFICITY.
Tissue: Monocyte.
[3]"Mycobacterium bovis Bacillus Calmette-Guerin and its cell wall complex induce a novel lysosomal membrane protein, SIMPLE, that bridges the missing link between lipopolysaccharide and p53-inducible gene, LITAF(PIG7), and estrogen-inducible gene, EET-1."
Moriwaki Y., Begum N.A., Kobayashi M., Matsumoto M., Toyoshima K., Seya T.
J. Biol. Chem. 276:23065-23076(2001) [PubMed: 11274176] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION, SUBCELLULAR LOCATION.
Tissue: Monocyte.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Oesophageal carcinoma.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Kidney, Pancreas, PNS and Skin.
[6]"WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins."
Ludes-Meyers J.H., Kil H., Bednarek A.K., Drake J., Bedford M.T., Aldaz C.M.
Oncogene 23:5049-5055(2004) [PubMed: 15064722] [Abstract]
Cited for: INTERACTION WITH WWOX, DOMAIN, MUTAGENESIS OF TYR-23 AND TYR-61.
[7]"LPS induces the interaction of a transcription factor, LPS-induced TNF-alpha factor, and STAT6(B) with effects on multiple cytokines."
Tang X., Marciano D.L., Leeman S.E., Amar S.
Proc. Natl. Acad. Sci. U.S.A. 102:5132-5137(2005) [PubMed: 15793005] [Abstract]
Cited for: INTERACTION WITH STAT6.
[8]"Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C."
Street V.A., Bennett C.L., Goldy J.D., Shirk A.J., Kleopa K.A., Tempel B.L., Lipe H.P., Scherer S.S., Bird T.D., Chance P.F.
Neurology 60:22-26(2003) [PubMed: 12525712] [Abstract]
Cited for: VARIANTS CMT1C SER-112; ASN-115 AND GLY-116.
[9]"PIG7/LITAF gene mutation and overexpression of its gene product in extramammary Paget's disease."
Matsumura Y., Matsumura Y., Nishigori C., Horio T., Miyachi Y.
Int. J. Cancer 111:218-223(2004) [PubMed: 15197774] [Abstract]
Cited for: VARIANT EMPD HIS-23.
[10]"Early onset neuropathy in a compound form of Charcot-Marie-Tooth disease."
Meggouh F., de Visser M., Arts W.F.M., De Coo R.I.F.M., van Schaik I.N., Baas F.
Ann. Neurol. 57:589-591(2005) [PubMed: 15786462] [Abstract]
Cited for: VARIANT CMT1C SER-112, VARIANT VAL-92.
[11]"SIMPLE mutations in Charcot-Marie-Tooth disease and the potential role of its protein product in protein degradation."
Saifi G.M., Szigeti K., Wiszniewski W., Shy M.E., Krajewski K., Hausmanowa-Petrusewicz I., Kochanski A., Reeser S., Mancias P., Butler I., Lupski J.R.
Hum. Mutat. 25:372-383(2005) [PubMed: 15776429] [Abstract]
Cited for: VARIANTS CMT1C MET-49; SER-112 AND VAL-122, VARIANT VAL-92.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF010312 mRNA. Translation: AAC39530.1.
U77396 mRNA. Translation: AAB36550.1.
AB034747 mRNA. Translation: BAB32547.1.
BX537543 mRNA. Translation: CAD97778.1.
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.
IPIIPI00017762.
IPI00645256.
RefSeqNP_001129944.1.
NP_001129945.1.
NP_004853.2.
UniGeneHs.459940

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

IntActQ99732. 2 interactions.

PTM databases

PhosphoSiteQ99732.

Genome annotation databases

EnsemblENSG00000189067. Homo sapiens. [Contig view]
GeneID9516.
KEGGhsa:9516.

Organism-specific databases

GeneCardsGC16M011549.
H-InvDBHIX0012818.
HIX0042981.
HGNCHGNC:16841. LITAF.
HPAHPA006960.
MIM601098. phenotype.
603795. gene.
Orphanet65753. Charcot-Marie-Tooth disease, type 1.
101083. Charcot-Marie-Tooth disease, type 1C.
PharmGKBPA134879224.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ99732.
OMAQ99732. HLQAFVG.

Gene expression databases

ArrayExpressQ99732.
BgeeQ99732.
CleanExHS_LITAF.
GermOnlineENSG00000189067. Homo sapiens.

Family and domain databases

InterProIPR006629. LITAF.
IPR019584. Znf_LITAF-like.
[Graphical view]
PfamPF10601. zf-LITAF-like. 1 hit.
[Graphical view]
SMARTSM00714. LITAF. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio35662.
SOURCESearch...

Entry information

Entry nameLITAF_HUMAN
AccessionPrimary (citable) accession number: Q99732
Secondary accession number(s): Q05DW0, Q9C0L6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: December 6, 2005
Last modified: June 16, 2009
This is version 75 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents