LITAF_MOUSE
ID LITAF_MOUSE Reviewed; 161 AA.
AC Q9JLJ0; Q9EQI0;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Lipopolysaccharide-induced tumor necrosis factor-alpha factor homolog;
DE Short=LPS-induced TNF-alpha factor homolog;
DE AltName: Full=Estrogen-enhanced transcript protein {ECO:0000303|PubMed:12355436};
DE Short=mEET {ECO:0000303|PubMed:12355436};
DE AltName: Full=LITAF-like protein;
DE AltName: Full=NEDD4 WW domain-binding protein 3;
GN Name=Litaf; Synonyms=N4wbp3, Tbx1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Thymus;
RX PubMed=12355436;
RX DOI=10.1002/1521-4141(2002010)32:10<2837::aid-immu2837>3.0.co;2-v;
RA Xie L.-P., Fu W.-X., Jin C., Dong X.-Y., Chen W.-F.;
RT "Negative regulation of monocyte chemoattractant protein-1 gene expression
RT by a mouse estrogen-enhanced transcript.";
RL Eur. J. Immunol. 32:2837-2846(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND
RP DEVELOPMENTAL STAGE.
RC TISSUE=Heart;
RX PubMed=15025820; DOI=10.1179/096805104225003780;
RA Bolcato-Bellemin A.-L., Mattei M.-G., Fenton M., Amar S.;
RT "Molecular cloning and characterization of mouse LITAF cDNA: role in the
RT regulation of tumor necrosis factor-alpha (TNF-alpha) gene expression.";
RL J. Endotoxin Res. 10:15-23(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Colon, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-130, INTERACTION WITH NEDD4, MUTAGENESIS OF
RP TYR-23 AND TYR-61, AND DOMAIN.
RC TISSUE=Embryo;
RX PubMed=11042109; DOI=10.1042/bj3510557;
RA Jolliffe C.N., Harvey K.F., Haines B.P., Parasivam G., Kumar S.;
RT "Identification of multiple proteins expressed in murine embryos as binding
RT partners for the WW domains of the ubiquitin-protein ligase Nedd4.";
RL Biochem. J. 351:557-565(2000).
RN [6]
RP FUNCTION, INTERACTION WITH STAT6, AND INDUCTION BY LIPOPOLYSACCHARIDE.
RX PubMed=15793005; DOI=10.1073/pnas.0501159102;
RA Tang X., Marciano D.L., Leeman S.E., Amar S.;
RT "LPS induces the interaction of a transcription factor, LPS-induced TNF-
RT alpha factor, and STAT6(B) with effects on multiple cytokines.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:5132-5137(2005).
RN [7]
RP FUNCTION.
RX PubMed=16954198; DOI=10.1073/pnas.0605988103;
RA Tang X., Metzger D., Leeman S., Amar S.;
RT "LPS-induced TNF-alpha factor (LITAF)-deficient mice express reduced LPS-
RT induced cytokine: Evidence for LITAF-dependent LPS signaling pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:13777-13782(2006).
RN [8]
RP FUNCTION.
RX PubMed=21980379; DOI=10.1371/journal.pone.0025083;
RA Tang X., Yang Y., Amar S.;
RT "Novel regulation of CCL2 gene expression by murine LITAF and STAT6B.";
RL PLoS ONE 6:E25083-E25083(2011).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22160695; DOI=10.1073/pnas.1111492108;
RA Merrill J.C., You J., Constable C., Leeman S.E., Amar S.;
RT "Whole-body deletion of LPS-induced TNF-alpha factor (LITAF) markedly
RT improves experimental endotoxic shock and inflammatory arthritis.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:21247-21252(2011).
RN [10]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RX PubMed=22729949; DOI=10.1002/glia.22371;
RA Somandin C., Gerber D., Pereira J.A., Horn M., Suter U.;
RT "LITAF (SIMPLE) regulates Wallerian degeneration after injury but is not
RT essential for peripheral nerve development and maintenance: implications
RT for Charcot-Marie-Tooth disease.";
RL Glia 60:1518-1528(2012).
RN [11]
RP FUNCTION.
RX PubMed=23166352; DOI=10.1083/jcb.201204137;
RA Lee S.M., Chin L.S., Li L.;
RT "Charcot-Marie-Tooth disease-linked protein SIMPLE functions with the ESCRT
RT machinery in endosomal trafficking.";
RL J. Cell Biol. 199:799-816(2012).
CC -!- FUNCTION: Plays a role in endosomal protein trafficking and in
CC targeting proteins for lysosomal degradation. Plays a role in targeting
CC endocytosed EGFR and ERGG3 for lysosomal degradation, and thereby helps
CC down-regulate downstream signaling cascades (PubMed:23166352). Helps
CC recruit the ESCRT complex components TSG101, HGS and STAM to
CC cytoplasmic membranes. Probably plays a role in regulating protein
CC degradation via its interaction with NEDD4 (By similarity). May also
CC contribute to the regulation of gene expression in the nucleus. Binds
CC DNA (in vitro) and may play a synergistic role with STAT6 in the
CC nucleus in regulating the expression of various cytokines
CC (PubMed:15793005, PubMed:21980379). May regulate the expression of
CC numerous cytokines, such as TNF, CCL2, CCL5, CXCL1, IL1A and IL10
CC (PubMed:12355436, PubMed:15025820, PubMed:16954198, PubMed:21980379,
CC PubMed:22160695). {ECO:0000250|UniProtKB:Q99732,
CC ECO:0000269|PubMed:12355436, ECO:0000269|PubMed:15025820,
CC ECO:0000269|PubMed:15793005, ECO:0000269|PubMed:16954198,
CC ECO:0000269|PubMed:21980379, ECO:0000269|PubMed:23166352}.
CC -!- SUBUNIT: Monomer. Interacts with NEDD4 (PubMed:11042109). Interacts
CC (via PSAP motif) with TSG101, a component of the ESCRT-I complex
CC (endosomal sorting complex required for transport I). Interacts with
CC WWOX. Interacts with STAM, a component of the ESCRT-0 complex; the
CC interaction is direct. Identified in a complex with STAM and HGS;
CC within this complex, interacts directly with STAM, but not with HGS.
CC Interacts with STAT6 (PubMed:15793005). {ECO:0000250|UniProtKB:Q99732,
CC ECO:0000269|PubMed:11042109, ECO:0000269|PubMed:15793005}.
CC -!- INTERACTION:
CC Q9JLJ0; P46935: Nedd4; NbExp=5; IntAct=EBI-643664, EBI-773516;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q99732}. Nucleus
CC {ECO:0000250|UniProtKB:Q99732}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q99732}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q99732}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q99732}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q99732}. Late endosome membrane
CC {ECO:0000250|UniProtKB:Q99732}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q99732}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q99732}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q99732}. Cell membrane
CC {ECO:0000250|UniProtKB:Q99732}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q99732}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q99732}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q99732}. Note=Associated with membranes of
CC lysosomes, early and late endosomes. Can translocate from the cytoplasm
CC into the nucleus (By similarity). Detected at Schmidt-Lanterman
CC incisures and in nodal regions of myelinating Schwann cells
CC (PubMed:22729949). {ECO:0000250|UniProtKB:Q99732,
CC ECO:0000269|PubMed:22729949}.
CC -!- TISSUE SPECIFICITY: Detected in brain, heart, lung, liver, spleen and
CC bone marrow (PubMed:22160695). Detected in myelinating Schwann cells in
CC sciatic nerve and in bone marrow-derived macrophages (at protein level)
CC (PubMed:22729949). Widely expressed. Highly expressed in liver.
CC {ECO:0000269|PubMed:12355436, ECO:0000269|PubMed:15025820,
CC ECO:0000269|PubMed:22160695, ECO:0000269|PubMed:22729949}.
CC -!- DEVELOPMENTAL STAGE: Expression in sciatic nerve is low in neonates,
CC culminates seven days after birth and decreases rapidly thereafter (at
CC protein level) (PubMed:22729949). Strong expression is detected at E.7
CC and drops at 11 dpc. {ECO:0000269|PubMed:15025820,
CC ECO:0000269|PubMed:22729949}.
CC -!- INDUCTION: Up-regulated in macrophages exposed to lipopolysaccharide
CC (LPS) (at protein level) (PubMed:15793005). By estrogen and
CC lipopolysaccharides (LPS). {ECO:0000269|PubMed:12355436,
CC ECO:0000269|PubMed:15025820, ECO:0000269|PubMed:15793005}.
CC -!- DOMAIN: The PPxY motif mediates interaction with WWOX and NEDD4.
CC {ECO:0000250|UniProtKB:Q99732}.
CC -!- DOMAIN: The LITAF domain is stabilized by a bound zinc ion. The LITAF
CC domain contains an amphipathic helix that mediates interaction with
CC lipid membranes. It interacts specifically with
CC phosphatidylethanolamine lipid headgroups, but not with
CC phosphoglycerol, phosphocholine, phosphoserine or
CC inositolhexakisphosphate. {ECO:0000250|UniProtKB:Q99732}.
CC -!- PTM: Phosphorylated on tyrosine residues in response to EGF.
CC {ECO:0000250|UniProtKB:Q99732}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are born at the
CC expected Mendelian rate and are fertile. Mutant mice display altered
CC responses to nerve crush injury, with higher numbers of macrophages in
CC injured nerves five days after nerve crush injury, but at later time
CC points macrophage numbers in injured nerves are normal. Bone marrow-
CC derived macrophages from mutant mice display increased migration in
CC response to CCL3, but not in the absence of CCL3 (PubMed:22729949).
CC Mutant mice show dramatically increased survival in response to a dose
CC of lipopolysaccharide (LPS) that causes rapid death of 40% of wild-type
CC mice (PubMed:22160695). {ECO:0000269|PubMed:22160695,
CC ECO:0000269|PubMed:22729949}.
CC -!- SIMILARITY: Belongs to the CDIP1/LITAF family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG44246.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF171100; AAF27312.1; -; mRNA.
DR EMBL; AF230522; AAO49168.1; -; mRNA.
DR EMBL; AK018578; BAB31289.1; -; mRNA.
DR EMBL; AK076162; BAC36228.1; -; mRNA.
DR EMBL; AK151053; BAE30070.1; -; mRNA.
DR EMBL; AK159533; BAE35161.1; -; mRNA.
DR EMBL; BC018559; AAH18559.1; -; mRNA.
DR EMBL; AF220207; AAG44246.1; ALT_INIT; mRNA.
DR CCDS; CCDS27958.1; -.
DR RefSeq; NP_064364.1; NM_019980.2.
DR RefSeq; XP_006522490.1; XM_006522427.1.
DR AlphaFoldDB; Q9JLJ0; -.
DR BioGRID; 208144; 2.
DR IntAct; Q9JLJ0; 2.
DR STRING; 10090.ENSMUSP00000023143; -.
DR iPTMnet; Q9JLJ0; -.
DR PhosphoSitePlus; Q9JLJ0; -.
DR SwissPalm; Q9JLJ0; -.
DR PaxDb; Q9JLJ0; -.
DR PRIDE; Q9JLJ0; -.
DR ProteomicsDB; 292265; -.
DR Antibodypedia; 1839; 297 antibodies from 36 providers.
DR DNASU; 56722; -.
DR Ensembl; ENSMUST00000023143; ENSMUSP00000023143; ENSMUSG00000022500.
DR Ensembl; ENSMUST00000117360; ENSMUSP00000112667; ENSMUSG00000022500.
DR GeneID; 56722; -.
DR KEGG; mmu:56722; -.
DR UCSC; uc007yen.2; mouse.
DR CTD; 9516; -.
DR MGI; MGI:1929512; Litaf.
DR VEuPathDB; HostDB:ENSMUSG00000022500; -.
DR eggNOG; ENOG502S2GM; Eukaryota.
DR GeneTree; ENSGT00940000155366; -.
DR HOGENOM; CLU_095549_3_0_1; -.
DR InParanoid; Q9JLJ0; -.
DR OMA; SCMDVHH; -.
DR OrthoDB; 354219at2759; -.
DR PhylomeDB; Q9JLJ0; -.
DR TreeFam; TF313294; -.
DR BioGRID-ORCS; 56722; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Litaf; mouse.
DR PRO; PR:Q9JLJ0; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9JLJ0; protein.
DR Bgee; ENSMUSG00000022500; Expressed in granulocyte and 275 other tissues.
DR ExpressionAtlas; Q9JLJ0; baseline and differential.
DR Genevisible; Q9JLJ0; MM.
DR GO; GO:0098559; C:cytoplasmic side of early endosome membrane; ISS:UniProtKB.
DR GO; GO:0098560; C:cytoplasmic side of late endosome membrane; ISS:UniProtKB.
DR GO; GO:0098574; C:cytoplasmic side of lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005765; C:lysosomal membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0050699; F:WW domain binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:MGI.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0001817; P:regulation of cytokine production; IBA:GO_Central.
DR GO; GO:0010935; P:regulation of macrophage cytokine production; IMP:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI.
DR InterPro; IPR006629; LITAF.
DR InterPro; IPR037519; LITAF_fam.
DR PANTHER; PTHR23292; PTHR23292; 1.
DR Pfam; PF10601; zf-LITAF-like; 1.
DR SMART; SM00714; LITAF; 1.
DR PROSITE; PS51837; LITAF; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; DNA-binding; Endosome; Golgi apparatus; Lysosome;
KW Membrane; Metal-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..161
FT /note="Lipopolysaccharide-induced tumor necrosis factor-
FT alpha factor homolog"
FT /id="PRO_0000084441"
FT DOMAIN 76..160
FT /note="LITAF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01181"
FT REGION 111..134
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000305"
FT MOTIF 20..23
FT /note="PPxY motif"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q99732"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q99732"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q99732"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q99732"
FT MUTAGEN 23
FT /note="Y->A: Abolishes interaction with NEDD4."
FT /evidence="ECO:0000269|PubMed:11042109"
FT MUTAGEN 61
FT /note="Y->A: No effect on interaction with NEDD4."
FT /evidence="ECO:0000269|PubMed:11042109"
SQ SEQUENCE 161 AA; 16946 MW; 7397F79C5AD0CD79 CRC64;
MSAPGPYQAA AGPSVVPTAP PTYEETVGVN SYYPTPPAPM PGPATGLITG PDGKGMNPPS
YYTQPVPVPN ANAIAVQTVY VQQPVSFYDR PVQMCCPSCS KMIVTQLSYN AGALTWLSCG
SLCLLGCVAG CCFIPFCVDA LQDVDHYCPN CKALLGTYKR L
