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FLASH GENE

Symbol

LITAF

contributors: mct - updated : 10-07-2018

HGNC name	lipopolysaccharide-induced TNF factor
HGNC id	16841

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CMT1C Charcot-Marie-Tooth disease, demyelinating, type 1C
Location	16p13.13      Physical location : 11.641.581 - 11.681.322
Synonym name	small integral membrane protein of lysosome/late endosome
	tumor protein p53 inducible protein 7
Synonym symbol(s)	PIG7, CMT1C, SIMPLE, TP53I7, FLJ38636, MGC116698, MGC116700, MGC116701

DNA

TYPE	functioning gene
STRUCTURE	39.74 kb     4 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004862 4 - 2642 NP_004853 - 161 - 2003 12655064 NM_001136472 4 - 2479 NP_001129944 - 161 - 2003 12655064 NM_001136473 5 - 2577 NP_001129945 - 152 - 2003 12655064

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive pharynx       highly Endocrine adrenal gland       highly Lymphoid/Immune spleen       predominantly Nervous nerve spinal nerve     highly Homo sapiens Reproductive female system uterus cervix   highly   male system prostate       Skin/Tegument skin

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous peripherous       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous Schawnn cell Homo sapiens

cell lineage
cell lines
fluid/secretion	blood

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminus containing two PPXY motifs that mediate protein-protein interactions with WW-domain containing proteins
	a PPXY motif
	P(S/T)AP motifs
	a transmembrane domain (TMD) embedded within the cysteine-rich (C-rich) region that anchors LITAF to the membrane
	C-terminus containing a highly conserved domain termed the SIMPLE-like domain (SLD)
	both the N- and C-termini of LITAF are exposed to the cytoplasm

mono polymer

aggregate

HOMOLOGY

interspecies	homolog to murine Litaf
	homolog to xenopus Xl.21754

Homologene

FAMILY	RING finger motif-containing subfamily of E3 ubiquitin ligases
	LITAF family

CATEGORY

regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,organelle,lysosome
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	LITAF mutants A111G, G112S, W116G, and T115N mislocalize from the late endosome/lysosome to the mitochondria while the mutants T49M, L122V, and P135T show partial mislocalization with a portion of the total protein present in the late endosome/lysosome and the remainder of the protein localized to the mitochondria

basic FUNCTION	playing an important role in the regulation of tumor necrosis factor alpha (TNFA)
	may be clathrin adaptor aiding in the retention of ubiquitinated proteins on to the endosomes
	E3 ubiquitin ligase playing a role in protein degradation
	multiple functional molecule whose sequence is identical to the small integral membrane protein of the lysosome/late endosome
	mediates the effect of AMPK by binding to a specific sequence in the promoter region
	may function as a tumor suppressor
	is a post-translationally inserted, C-tail-anchored membrane protein
	transcription factor that mediates TNF1 expression (
	LITAF function is not absolutely required for peripheral nerve development and maintenance
	function of LITAF as a regulator of endosomal trafficking, providing evidence linking dysregulated endosomal trafficking to CMT pathogenesis
	LITAF traffics through the secretory pathway to the late endosome/lysosome
	is a novel player in multivesicular bodies (MVBs) regulation
	is an endosome-associated integral membrane protein important for multivesicular body sorting
	is a monotopic membrane protein whose membrane integration is stabilised by a zinc finger

CELLULAR PROCESS	nucleotide, transcription, regulation
	protein, degradation
	protein, ubiquitin dependent proteolysis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	LITAF forms a complex with human STAT6, which translocates into the nucleus to upregulate cytokine transcription (

INTERACTION

DNA

RNA

small molecule

protein	binding with TNF
	ITCH, a WW-domain containing protein, and LITAF strongly interact and this interaction depends on the two PPXY motifs in the N-terminus of LITAF
	LITAF interacted and colocalized with endosomal
	complex required for transport (ESCRT) components STAM, HGS, and TSG101 on early endosomes and functioned with the ESCRT machinery in the control of endosome-to-lysosome trafficking
	BCL6-mediated transcriptional repression of LITAF may inhibit autophagy in B cells during the germinal centre reaction sorting
	TWIST1-binding sequences associated with CHST11, LITAF, ROR2, and SPATA5 also bound the potential TWIST1 cofactor RREB1

cell & other

REGULATION

activated by	AMPK (AMPK activation upregulates the transcription of LITAF)

induced by

by lipopolysaccharides (lps) or TP53

ASSOCIATED DISORDERS

corresponding disease(s)

CMT1C

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral         silenced by promoter hypermethylation in germinal centre-derived B-cell lymphomas

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS