ID LITAF_HUMAN Reviewed; 161 AA. AC Q99732; D3DUG1; G5E9K0; Q05DW0; Q9C0L6; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 2. DT 24-JAN-2024, entry version 198. DE RecName: Full=Lipopolysaccharide-induced tumor necrosis factor-alpha factor {ECO:0000303|PubMed:10200294}; DE Short=LPS-induced TNF-alpha factor {ECO:0000303|PubMed:10200294}; DE AltName: Full=Small integral membrane protein of lysosome/late endosome {ECO:0000303|PubMed:11274176}; DE AltName: Full=p53-induced gene 7 protein {ECO:0000303|PubMed:11274176}; GN Name=LITAF; GN Synonyms=PIG7 {ECO:0000303|PubMed:11274176, GN ECO:0000303|PubMed:15197774}, SIMPLE {ECO:0000303|PubMed:11274176}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INDUCTION BY TP53. RC TISSUE=Colon cancer; RX PubMed=9305847; DOI=10.1038/38525; RA Polyak K., Xia Y., Zweier J.L., Kinzler K.W., Vogelstein B.; RT "A model for p53-induced apoptosis."; RL Nature 389:300-306(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INDUCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Monocyte; RX PubMed=10200294; DOI=10.1073/pnas.96.8.4518; RA Myokai F., Takashiba S., Lebo R., Amar S.; RT "A novel lipopolysaccharide-induced transcription factor regulating tumor RT necrosis factor alpha gene expression: molecular cloning, sequencing, RT characterization, and chromosomal assignment."; RL Proc. Natl. Acad. Sci. U.S.A. 96:4518-4523(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION, AND RP SUBCELLULAR LOCATION. RC TISSUE=Monocyte; RX PubMed=11274176; DOI=10.1074/jbc.m011660200; RA Moriwaki Y., Begum N.A., Kobayashi M., Matsumoto M., Toyoshima K., Seya T.; RT "Mycobacterium bovis Bacillus Calmette-Guerin and its cell wall complex RT induce a novel lysosomal membrane protein, SIMPLE, that bridges the missing RT link between lipopolysaccharide and p53-inducible gene, LITAF(PIG7), and RT estrogen-inducible gene, EET-1."; RL J. Biol. Chem. 276:23065-23076(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Hair follicle dermal papilla; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Esophageal carcinoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney, Pancreas, PNS, and Skin; 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 [9] RP INTERACTION WITH WWOX, DOMAIN, AND MUTAGENESIS OF TYR-23 AND TYR-61. RX PubMed=15064722; DOI=10.1038/sj.onc.1207680; RA Ludes-Meyers J.H., Kil H., Bednarek A.K., Drake J., Bedford M.T., RA Aldaz C.M.; RT "WWOX binds the specific proline-rich ligand PPXY: identification of RT candidate interacting proteins."; RL Oncogene 23:5049-5055(2004). RN [10] RP INTERACTION WITH NEDD4 AND TSG101, CHARACTERIZATION OF VARIANTS CMT1C RP SER-112; ASN-115 AND GLY-116, AND MUTAGENESIS OF 17-PRO--ALA-19 AND TYR-23. RX PubMed=16118794; DOI=10.1002/jnr.20628; RA Shirk A.J., Anderson S.K., Hashemi S.H., Chance P.F., Bennett C.L.; RT "SIMPLE interacts with NEDD4 and TSG101: evidence for a role in lysosomal RT sorting and implications for Charcot-Marie-Tooth disease."; RL J. Neurosci. Res. 82:43-50(2005). RN [11] RP FUNCTION, INTERACTION WITH STAT6, SUBCELLULAR LOCATION, AND INDUCTION BY RP 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 [12] RP SUBCELLULAR LOCATION. 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 [13] RP SUBCELLULAR LOCATION, MUTAGENESIS OF PRO-135, AND CHARACTERIZATION OF RP VARIANT CMT1C GLY-116. RX PubMed=21896645; DOI=10.1242/jcs.087114; RA Lee S.M., Olzmann J.A., Chin L.S., Li L.; RT "Mutations associated with Charcot-Marie-Tooth disease cause SIMPLE protein RT mislocalization and degradation by the proteasome and aggresome-autophagy RT pathways."; RL J. Cell Sci. 124:3319-3331(2011). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH TSG101; STAM AND RP HGS, PHOSPHORYLATION, MUTAGENESIS OF 17-PRO--PRO-20 AND PRO-135, AND RP CHARACTERIZATION OF VARIANT CMT1C GLY-116. 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). RN [15] RP 3D-STRUCTURE MODELING, NMR SECONDARY STRUCTURE ANALYSIS, SUBCELLULAR RP LOCATION, TOPOLOGY, ZINC-BINDING, SUBUNIT, INTERACTION WITH NEDD4, DOMAIN, RP AND MUTAGENESIS OF TYR-23; TYR-61 AND VAL-144. RX PubMed=27927196; DOI=10.1186/s12915-016-0332-8; RA Ho A.K., Wagstaff J.L., Manna P.T., Wartosch L., Qamar S., Garman E.F., RA Freund S.M., Roberts R.C.; RT "The topology, structure and PE interaction of LITAF underpin a Charcot- RT Marie-Tooth disease type 1C."; RL BMC Biol. 14:109-109(2016). RN [16] RP ZINC-BINDING, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF CYS-96 AND RP CYS-148, AND DOMAIN. RX PubMed=27582497; DOI=10.1042/bcj20160657; RA Qin W., Wunderley L., Barrett A.L., High S., Woodman P.G.; RT "The Charcot Marie Tooth disease protein LITAF is a zinc-binding monotopic RT membrane protein."; RL Biochem. J. 473:3965-3978(2016). RN [17] RP VARIANTS CMT1C SER-112; ASN-115 AND GLY-116. RX PubMed=12525712; DOI=10.1212/wnl.60.1.22; RA Street V.A., Bennett C.L., Goldy J.D., Shirk A.J., Kleopa K.A., RA Tempel B.L., Lipe H.P., Scherer S.S., Bird T.D., Chance P.F.; RT "Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot- RT Marie-Tooth disease 1C."; RL Neurology 60:22-26(2003). RN [18] RP VARIANT EMPD HIS-23. RX PubMed=15197774; DOI=10.1002/ijc.20251; RA Matsumura Y., Matsumura Y., Nishigori C., Horio T., Miyachi Y.; RT "PIG7/LITAF gene mutation and overexpression of its gene product in RT extramammary Paget's disease."; RL Int. J. Cancer 111:218-223(2004). RN [19] RP VARIANT CMT1C SER-112, AND VARIANT VAL-92. RX PubMed=15786462; DOI=10.1002/ana.20434; RA Meggouh F., de Visser M., Arts W.F.M., De Coo R.I.F.M., van Schaik I.N., RA Baas F.; RT "Early onset neuropathy in a compound form of Charcot-Marie-Tooth RT disease."; RL Ann. Neurol. 57:589-591(2005). RN [20] RP VARIANTS CMT1C MET-49; SER-112 AND VAL-122, VARIANT VAL-92, AND PUTATIVE RP FUNCTION. RX PubMed=15776429; DOI=10.1002/humu.20153; RA Saifi G.M., Szigeti K., Wiszniewski W., Shy M.E., Krajewski K., RA Hausmanowa-Petrusewicz I., Kochanski A., Reeser S., Mancias P., Butler I., RA Lupski J.R.; RT "SIMPLE mutations in Charcot-Marie-Tooth disease and the potential role of RT its protein product in protein degradation."; RL Hum. Mutat. 25:372-383(2005). RN [21] RP VARIANT CMT1C SER-112. RX PubMed=24604904; DOI=10.1136/jnnp-2013-306740; RA Klein C.J., Middha S., Duan X., Wu Y., Litchy W.J., Gu W., Dyck P.J., RA Gavrilova R.H., Smith D.I., Kocher J.P., Dyck P.J.; RT "Application of whole exome sequencing in undiagnosed inherited RT polyneuropathies."; RL J. Neurol. Neurosurg. Psych. 85:1265-1272(2014). CC -!- FUNCTION: Plays a role in endosomal protein trafficking and in CC targeting proteins for lysosomal degradation (PubMed:23166352). Plays a CC role in targeting endocytosed EGFR and ERGG3 for lysosomal degradation, CC and thereby helps down-regulate downstream signaling cascades CC (PubMed:23166352). Helps recruit the ESCRT complex components TSG101, CC HGS and STAM to cytoplasmic membranes (PubMed:23166352). Probably plays CC a role in regulating protein degradation via its interaction with NEDD4 CC (PubMed:15776429). May also contribute to the regulation of gene CC expression in the nucleus (PubMed:10200294, PubMed:15793005). Binds DNA CC (in vitro) and may play a synergistic role with STAT6 in the nucleus in CC regulating the expression of various cytokines (PubMed:15793005). May CC regulate the expression of numerous cytokines, such as TNF, CCL2, CCL5, CC CXCL1, IL1A and IL10 (PubMed:10200294, PubMed:15793005). CC {ECO:0000269|PubMed:15793005, ECO:0000269|PubMed:23166352, CC ECO:0000303|PubMed:15776429, ECO:0000305|PubMed:10200294}. CC -!- SUBUNIT: Monomer (PubMed:27927196). Interacts with NEDD4 CC (PubMed:16118794, PubMed:27927196). Interacts (via PSAP motif) with CC TSG101, a component of the ESCRT-I complex (endosomal sorting complex CC required for transport I) (PubMed:16118794). Interacts with WWOX CC (PubMed:15064722). Interacts with STAM, a component of the ESCRT-0 CC complex; the interaction is direct (PubMed:23166352). Identified in a CC complex with STAM and HGS; within this complex, interacts directly with CC STAM, but not with HGS (PubMed:23166352). Interacts with STAT6 CC (PubMed:15793005). {ECO:0000269|PubMed:15064722, CC ECO:0000269|PubMed:16118794, ECO:0000269|PubMed:23166352, CC ECO:0000269|PubMed:27927196, ECO:0000305|PubMed:15793005}. CC -!- INTERACTION: CC Q99732; Q9UKA4: AKAP11; NbExp=3; IntAct=EBI-725647, EBI-1049491; CC Q99732; Q03989: ARID5A; NbExp=3; IntAct=EBI-725647, EBI-948603; CC Q99732; Q9BVU5: ARL17; NbExp=3; IntAct=EBI-725647, EBI-25857117; CC Q99732; O95817: BAG3; NbExp=7; IntAct=EBI-725647, EBI-747185; CC Q99732; P80723: BASP1; NbExp=3; IntAct=EBI-725647, EBI-358583; CC Q99732; Q13137: CALCOCO2; NbExp=7; IntAct=EBI-725647, EBI-739580; CC Q99732; Q9HC96: CAPN10; NbExp=3; IntAct=EBI-725647, EBI-3915761; CC Q99732; P83916: CBX1; NbExp=3; IntAct=EBI-725647, EBI-78129; CC Q99732; Q9BXL8: CDCA4; NbExp=3; IntAct=EBI-725647, EBI-1773949; CC Q99732; Q8NI60: COQ8A; NbExp=3; IntAct=EBI-725647, EBI-745535; CC Q99732; Q92828: CORO2A; NbExp=3; IntAct=EBI-725647, EBI-2835660; CC Q99732; Q02930-3: CREB5; NbExp=3; IntAct=EBI-725647, EBI-10192698; CC Q99732; Q9UN19: DAPP1; NbExp=3; IntAct=EBI-725647, EBI-3918199; CC Q99732; Q15038: DAZAP2; NbExp=5; IntAct=EBI-725647, EBI-724310; CC Q99732; Q9NR30: DDX21; NbExp=3; IntAct=EBI-725647, EBI-357942; CC Q99732; Q92608-2: DOCK2; NbExp=3; IntAct=EBI-725647, EBI-25875570; CC Q99732; Q9Y6I3-3: EPN1; NbExp=3; IntAct=EBI-725647, EBI-12026538; CC Q99732; O95208-2: EPN2; NbExp=5; IntAct=EBI-725647, EBI-12135243; CC Q99732; I6L9I8: EPN3; NbExp=5; IntAct=EBI-725647, EBI-12866582; CC Q99732; Q9NZ52-2: GGA3; NbExp=3; IntAct=EBI-725647, EBI-12075758; CC Q99732; O14964: HGS; NbExp=8; IntAct=EBI-725647, EBI-740220; CC Q99732; O00291: HIP1; NbExp=6; IntAct=EBI-725647, EBI-473886; CC Q99732; P37235: HPCAL1; NbExp=4; IntAct=EBI-725647, EBI-749311; CC Q99732; Q9UM19: HPCAL4; NbExp=6; IntAct=EBI-725647, EBI-744820; CC Q99732; Q96T52-2: IMMP2L; NbExp=3; IntAct=EBI-725647, EBI-25907627; CC Q99732; Q9NZI2-2: KCNIP1; NbExp=3; IntAct=EBI-725647, EBI-22452746; CC Q99732; Q6PIL6: KCNIP4; NbExp=3; IntAct=EBI-725647, EBI-1051469; CC Q99732; P13473-2: LAMP2; NbExp=3; IntAct=EBI-725647, EBI-21591415; CC Q99732; Q8TCE9: LGALS14; NbExp=3; IntAct=EBI-725647, EBI-10274069; CC Q99732; Q99732: LITAF; NbExp=2; IntAct=EBI-725647, EBI-725647; CC Q99732; Q9BYD3: MRPL4; NbExp=3; IntAct=EBI-725647, EBI-721368; CC Q99732; O75113: N4BP1; NbExp=3; IntAct=EBI-725647, EBI-5278391; CC Q99732; P61601: NCALD; NbExp=5; IntAct=EBI-725647, EBI-749635; CC Q99732; P46934: NEDD4; NbExp=6; IntAct=EBI-725647, EBI-726944; CC Q99732; Q96CV9: OPTN; NbExp=3; IntAct=EBI-725647, EBI-748974; CC Q99732; Q96CV9-2: OPTN; NbExp=3; IntAct=EBI-725647, EBI-9091423; CC Q99732; Q7Z3K3: POGZ; NbExp=3; IntAct=EBI-725647, EBI-1389308; CC Q99732; Q9NS23-4: RASSF1; NbExp=3; IntAct=EBI-725647, EBI-438710; CC Q99732; Q86WH2: RASSF3; NbExp=4; IntAct=EBI-725647, EBI-2845202; CC Q99732; Q96HR9: REEP6; NbExp=8; IntAct=EBI-725647, EBI-750345; CC Q99732; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-725647, EBI-14065960; CC Q99732; Q8N8N0: RNF152; NbExp=3; IntAct=EBI-725647, EBI-2129725; CC Q99732; Q96D59: RNF183; NbExp=3; IntAct=EBI-725647, EBI-743938; CC Q99732; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-725647, EBI-751555; CC Q99732; P62979: RPS27A; NbExp=3; IntAct=EBI-725647, EBI-357375; CC Q99732; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-725647, EBI-11528848; CC Q99732; Q99717: SMAD5; NbExp=3; IntAct=EBI-725647, EBI-6391136; CC Q99732; Q9C0H9-4: SRCIN1; NbExp=3; IntAct=EBI-725647, EBI-25907611; CC Q99732; O75886: STAM2; NbExp=11; IntAct=EBI-725647, EBI-373258; CC Q99732; Q86VP1: TAX1BP1; NbExp=3; IntAct=EBI-725647, EBI-529518; CC Q99732; Q96HP8: TMEM176A; NbExp=3; IntAct=EBI-725647, EBI-2800645; CC Q99732; Q15025: TNIP1; NbExp=3; IntAct=EBI-725647, EBI-357849; CC Q99732; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-725647, EBI-2509913; CC Q99732; O60784-2: TOM1; NbExp=3; IntAct=EBI-725647, EBI-12117154; CC Q99732; Q99816: TSG101; NbExp=3; IntAct=EBI-725647, EBI-346882; CC Q99732; P62987: UBA52; NbExp=3; IntAct=EBI-725647, EBI-357304; CC Q99732; O14933: UBE2L6; NbExp=3; IntAct=EBI-725647, EBI-2129974; CC Q99732; Q9UMX0: UBQLN1; NbExp=4; IntAct=EBI-725647, EBI-741480; CC Q99732; Q9UMX0-2: UBQLN1; NbExp=7; IntAct=EBI-725647, EBI-10173939; CC Q99732; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-725647, EBI-947187; CC Q99732; O95231: VENTX; NbExp=3; IntAct=EBI-725647, EBI-10191303; CC Q99732; O15195-2: VILL; NbExp=3; IntAct=EBI-725647, EBI-21845957; CC Q99732; P62760: VSNL1; NbExp=3; IntAct=EBI-725647, EBI-740943; CC Q99732; Q9NZC7: WWOX; NbExp=5; IntAct=EBI-725647, EBI-4320739; CC Q99732; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-725647, EBI-12040603; CC Q99732; O00308: WWP2; NbExp=3; IntAct=EBI-725647, EBI-743923; CC Q99732; Q15915: ZIC1; NbExp=3; IntAct=EBI-725647, EBI-11963196; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15793005}. Nucleus CC {ECO:0000269|PubMed:15793005, ECO:0000269|PubMed:16954198}. Lysosome CC membrane {ECO:0000269|PubMed:11274176, ECO:0000269|PubMed:27582497}; CC Peripheral membrane protein {ECO:0000269|PubMed:11274176}; Cytoplasmic CC side {ECO:0000269|PubMed:11274176}. Early endosome membrane CC {ECO:0000269|PubMed:21896645, ECO:0000269|PubMed:23166352, CC ECO:0000269|PubMed:27582497}. Late endosome membrane CC {ECO:0000269|PubMed:27582497}. Endosome membrane CC {ECO:0000269|PubMed:27927196}; Peripheral membrane protein CC {ECO:0000269|PubMed:27927196}; Cytoplasmic side CC {ECO:0000269|PubMed:27927196}. Cell membrane CC {ECO:0000269|PubMed:16118794, ECO:0000269|PubMed:27582497}; Peripheral CC membrane protein {ECO:0000269|PubMed:27582497}; Cytoplasmic side CC {ECO:0000269|PubMed:27582497}. Golgi apparatus membrane CC {ECO:0000269|PubMed:16118794}. Note=Associated with membranes of CC lysosomes, early and late endosomes (PubMed:11274176, PubMed:27927196, CC PubMed:27582497). Can translocate from the cytoplasm into the nucleus CC (PubMed:15793005). Detected at Schmidt-Lanterman incisures and in nodal CC regions of myelinating Schwann cells (By similarity). CC {ECO:0000250|UniProtKB:Q9JLJ0, ECO:0000269|PubMed:11274176, CC ECO:0000269|PubMed:15793005, ECO:0000269|PubMed:27582497, CC ECO:0000269|PubMed:27927196}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q99732-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99732-2; Sequence=VSP_016461; CC Name=3; CC IsoId=Q99732-3; Sequence=VSP_045701; CC -!- TISSUE SPECIFICITY: Ubiquitously and abundantly expressed. Expressed CC predominantly in the placenta, peripheral blood leukocytes, lymph nodes CC and spleen. {ECO:0000269|PubMed:10200294, ECO:0000269|PubMed:11274176}. CC -!- INDUCTION: Up-regulated by bacterial lipopolysaccharide (LPS) (at CC protein level) (PubMed:15793005). By bacterial lipopolysaccharide (LPS) CC and by p53/TP53 (PubMed:9305847, PubMed:10200294). In monocytes by the CC Bacillus Calmette-Guerin (BCG) (PubMed:11274176). CC {ECO:0000269|PubMed:10200294, ECO:0000269|PubMed:11274176, CC ECO:0000269|PubMed:15793005, ECO:0000269|PubMed:9305847}. CC -!- DOMAIN: The PPxY motif mediates interaction with WWOX and NEDD4. CC {ECO:0000269|PubMed:15064722, ECO:0000269|PubMed:27927196}. CC -!- DOMAIN: The LITAF domain is stabilized by a bound zinc ion CC (PubMed:27927196, PubMed:27582497). The LITAF domain contains an CC amphipathic helix that mediates interaction with lipid membranes CC (PubMed:23166352, PubMed:27927196, PubMed:27582497). It interacts CC specifically with phosphatidylethanolamine lipid headgroups, but not CC with phosphoglycerol, phosphocholine, phosphoserine or CC inositolhexakisphosphate (PubMed:27927196). CC {ECO:0000269|PubMed:23166352, ECO:0000269|PubMed:27582497, CC ECO:0000269|PubMed:27927196}. CC -!- PTM: Phosphorylated on tyrosine residues in response to EGF. CC {ECO:0000269|PubMed:23166352}. CC -!- DISEASE: Charcot-Marie-Tooth disease, demyelinating, 1C (CMT1C) CC [MIM:601098]: A dominant demyelinating form of Charcot-Marie-Tooth CC disease, a disorder of the peripheral nervous system, characterized by CC progressive weakness and atrophy, initially of the peroneal muscles and CC later of the distal muscles of the arms. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathies (designated CMT1 when they are dominantly inherited) and CC primary peripheral axonal neuropathies (CMT2). Demyelinating CC neuropathies are characterized by severely reduced nerve conduction CC velocities (less than 38 m/sec), segmental demyelination and CC remyelination with onion bulb formations on nerve biopsy, slowly CC progressive distal muscle atrophy and weakness, absent deep tendon CC reflexes, and hollow feet. {ECO:0000269|PubMed:12525712, CC ECO:0000269|PubMed:15776429, ECO:0000269|PubMed:15786462, CC ECO:0000269|PubMed:16118794, ECO:0000269|PubMed:21896645, CC ECO:0000269|PubMed:23166352, ECO:0000269|PubMed:24604904}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Note=Defects in LITAF may be involved in extramammary Paget CC disease (EMPD) carcinogenesis. EMPD is a cancerous disease representing CC about 8% of all malignant skin cancers; it usually appears in the CC anogenital area and can be fatal by metastasizing to internal organs CC when left untreated for a long time. The clinical features are usually CC those of eczematous eruptions with weeping and crust formation. CC {ECO:0000269|PubMed:15197774}. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to a frameshift that creates an CC unconventional splicing site. Data inferred from this isoform must be CC interpreted with caution. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the CDIP1/LITAF family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="https://uantwerpen.vib.be/CMTMutations"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF010312; AAC39530.1; -; mRNA. DR EMBL; U77396; AAB36550.1; -; mRNA. DR EMBL; AB034747; BAB32547.1; -; mRNA. DR EMBL; AK095955; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BX537543; CAD97778.1; -; mRNA. DR EMBL; AC007616; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC099489; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471112; EAW85150.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85151.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85152.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85153.1; -; Genomic_DNA. DR EMBL; BC000053; AAH00053.1; -; mRNA. DR EMBL; BC008309; AAH08309.1; -; mRNA. DR EMBL; BC016491; AAH16491.1; -; mRNA. DR EMBL; BC039840; AAH39840.1; -; mRNA. DR EMBL; BC046154; AAH46154.1; -; mRNA. DR EMBL; BC096063; AAH96063.1; -; mRNA. DR EMBL; BC096065; AAH96065.1; -; mRNA. DR EMBL; BC096066; AAH96066.1; -; mRNA. DR EMBL; BC101401; AAI01402.1; -; mRNA. DR EMBL; BC101402; AAI01403.1; -; mRNA. DR EMBL; BC101969; AAI01970.1; -; mRNA. DR CCDS; CCDS32386.1; -. [Q99732-1] DR CCDS; CCDS45411.1; -. [Q99732-3] DR RefSeq; NP_001129944.1; NM_001136472.1. [Q99732-1] DR RefSeq; NP_001129945.1; NM_001136473.1. [Q99732-3] DR RefSeq; NP_004853.2; NM_004862.3. [Q99732-1] DR RefSeq; XP_006721045.1; XM_006720982.2. [Q99732-1] DR RefSeq; XP_006721046.1; XM_006720983.3. [Q99732-1] DR RefSeq; XP_006721047.1; XM_006720984.3. [Q99732-1] DR RefSeq; XP_006721048.1; XM_006720985.3. DR RefSeq; XP_016879385.1; XM_017023896.1. DR AlphaFoldDB; Q99732; -. DR BioGRID; 114893; 79. DR CORUM; Q99732; -. DR IntAct; Q99732; 87. DR STRING; 9606.ENSP00000459533; -. DR BindingDB; Q99732; -. DR iPTMnet; Q99732; -. DR PhosphoSitePlus; Q99732; -. DR SwissPalm; Q99732; -. DR BioMuta; LITAF; -. DR DMDM; 83304387; -. DR jPOST; Q99732; -. DR MassIVE; Q99732; -. DR PaxDb; 9606-ENSP00000459533; -. DR PeptideAtlas; Q99732; -. DR ProteomicsDB; 33961; -. DR ProteomicsDB; 78448; -. [Q99732-1] DR ProteomicsDB; 78449; -. [Q99732-2] DR Pumba; Q99732; -. DR Antibodypedia; 1839; 318 antibodies from 36 providers. DR DNASU; 9516; -. DR Ensembl; ENST00000339430.9; ENSP00000340118.5; ENSG00000189067.14. [Q99732-1] DR Ensembl; ENST00000413364.6; ENSP00000397958.2; ENSG00000189067.14. [Q99732-3] DR Ensembl; ENST00000570904.5; ENSP00000459138.1; ENSG00000189067.14. [Q99732-1] DR Ensembl; ENST00000571688.5; ENSP00000459533.1; ENSG00000189067.14. [Q99732-1] DR Ensembl; ENST00000574763.5; ENSP00000461813.1; ENSG00000189067.14. [Q99732-1] DR Ensembl; ENST00000576036.5; ENSP00000461667.1; ENSG00000189067.14. [Q99732-1] DR Ensembl; ENST00000622633.5; ENSP00000483114.1; ENSG00000189067.14. [Q99732-1] DR GeneID; 9516; -. DR KEGG; hsa:9516; -. DR MANE-Select; ENST00000622633.5; ENSP00000483114.1; NM_001136472.2; NP_001129944.1. DR UCSC; uc002daz.4; human. [Q99732-1] DR AGR; HGNC:16841; -. DR CTD; 9516; -. DR DisGeNET; 9516; -. DR GeneCards; LITAF; -. DR GeneReviews; LITAF; -. DR HGNC; HGNC:16841; LITAF. DR HPA; ENSG00000189067; Low tissue specificity. DR MalaCards; LITAF; -. DR MIM; 601098; phenotype. DR MIM; 603795; gene. DR neXtProt; NX_Q99732; -. DR OpenTargets; ENSG00000189067; -. DR Orphanet; 101083; Charcot-Marie-Tooth disease type 1C. DR PharmGKB; PA134879224; -. DR VEuPathDB; HostDB:ENSG00000189067; -. DR eggNOG; ENOG502S2GM; Eukaryota. DR GeneTree; ENSGT00940000155366; -. DR HOGENOM; CLU_095549_3_0_1; -. DR InParanoid; Q99732; -. DR OMA; VTFYDRP; -. DR OrthoDB; 1383925at2759; -. DR PhylomeDB; Q99732; -. DR TreeFam; TF313294; -. DR PathwayCommons; Q99732; -. DR SignaLink; Q99732; -. DR SIGNOR; Q99732; -. DR BioGRID-ORCS; 9516; 20 hits in 1172 CRISPR screens. DR ChiTaRS; LITAF; human. DR GeneWiki; LITAF; -. DR GenomeRNAi; 9516; -. DR Pharos; Q99732; Tbio. DR PRO; PR:Q99732; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q99732; Protein. DR Bgee; ENSG00000189067; Expressed in blood and 208 other cell types or tissues. DR ExpressionAtlas; Q99732; baseline and differential. DR GO; GO:0098559; C:cytoplasmic side of early endosome membrane; IDA:UniProtKB. DR GO; GO:0098560; C:cytoplasmic side of late endosome membrane; IDA:UniProtKB. DR GO; GO:0098574; C:cytoplasmic side of lysosomal membrane; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005765; C:lysosomal membrane; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IMP:UniProtKB. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:NTNU_SB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0050699; F:WW domain binding; IPI:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; HMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:NTNU_SB. DR GO; GO:0001817; P:regulation of cytokine production; IBA:GO_Central. DR GO; GO:0010935; P:regulation of macrophage cytokine production; IEA:Ensembl. DR InterPro; IPR006629; LITAF. DR InterPro; IPR037519; LITAF_fam. DR PANTHER; PTHR23292; LIPOPOLYSACCHARIDE-INDUCED TUMOR NECROSIS FACTOR-ALPHA FACTOR; 1. DR PANTHER; PTHR23292:SF2; LIPOPOLYSACCHARIDE-INDUCED TUMOR NECROSIS FACTOR-ALPHA FACTOR; 1. DR Pfam; PF10601; zf-LITAF-like; 1. DR SMART; SM00714; LITAF; 1. DR PROSITE; PS51837; LITAF; 1. DR Genevisible; Q99732; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Charcot-Marie-Tooth disease; KW Cytoplasm; Disease variant; DNA-binding; Endosome; Golgi apparatus; KW Lysosome; Membrane; Metal-binding; Neurodegeneration; Neuropathy; Nucleus; KW Phosphoprotein; Reference proteome; Transcription; KW Transcription regulation; Zinc. FT CHAIN 1..161 FT /note="Lipopolysaccharide-induced tumor necrosis factor- FT alpha factor" FT /id="PRO_0000084440" FT DOMAIN 76..160 FT /note="LITAF" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01181" FT REGION 1..22 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 111..134 FT /note="Membrane-binding amphipathic helix" FT /evidence="ECO:0000269|PubMed:27927196" FT MOTIF 17..20 FT /note="PSAP motif; important for interaction with TSG101" FT /evidence="ECO:0000269|PubMed:16118794, FT ECO:0000269|PubMed:23166352" FT MOTIF 20..23 FT /note="PPxY motif" FT /evidence="ECO:0000269|PubMed:15064722, FT ECO:0000269|PubMed:23166352, ECO:0000269|PubMed:27927196" FT COMPBIAS 7..22 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 96 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000305|PubMed:27582497, FT ECO:0000305|PubMed:27927196" FT BINDING 99 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000305|PubMed:27927196" FT BINDING 148 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000305|PubMed:27582497, FT ECO:0000305|PubMed:27927196" FT BINDING 151 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000305|PubMed:27927196" FT VAR_SEQ 127..161 FT /note="CIAGCCFIPFCVDALQDVDHYCPNCRALLGTYKRL -> VHSGLLLHPLLRG FT CPAGRGPLLSQLQSSPGHLQAFVGLSQTWREPGAAGSPFHLSSSFTPGGGSALVVSPLQ FT GAHLHVFFWGEYVAKLTNLQTPEIAAWSRA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10200294, FT ECO:0000303|PubMed:9305847" FT /id="VSP_016461" FT VAR_SEQ 127..161 FT /note="CIAGCCFIPFCVDALQDVDHYCPNCRALLGTYKRL -> QECSGTIVALRSF FT DLLGSCNPPSSAS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045701" FT VARIANT 23 FT /note="Y -> H (in one EMPD primary tumor; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:15197774" FT /id="VAR_024014" FT VARIANT 49 FT /note="T -> M (in CMT1C; dbSNP:rs141862602)" FT /evidence="ECO:0000269|PubMed:15776429" FT /id="VAR_024015" FT VARIANT 92 FT /note="I -> V (in dbSNP:rs4280262)" FT /evidence="ECO:0000269|PubMed:15776429, FT ECO:0000269|PubMed:15786462" FT /id="VAR_024016" FT VARIANT 112 FT /note="G -> S (in CMT1C; does not abolish interaction with FT NEDD4 and TSG101; dbSNP:rs104894519)" FT /evidence="ECO:0000269|PubMed:12525712, FT ECO:0000269|PubMed:15776429, ECO:0000269|PubMed:15786462, FT ECO:0000269|PubMed:16118794, ECO:0000269|PubMed:24604904" FT /id="VAR_024017" FT VARIANT 115 FT /note="T -> N (in CMT1C; does not abolish interaction with FT NEDD4 and TSG101; dbSNP:rs104894520)" FT /evidence="ECO:0000269|PubMed:12525712, FT ECO:0000269|PubMed:16118794" FT /id="VAR_024018" FT VARIANT 116 FT /note="W -> G (in CMT1C; decreases protein stability and FT association with early endosome membranes; impaired FT function in targeting endocytosed proteins for lysosomal FT degradation; does not abolish interaction with NEDD4 and FT TSG101; dbSNP:rs104894521)" FT /evidence="ECO:0000269|PubMed:12525712, FT ECO:0000269|PubMed:16118794, ECO:0000269|PubMed:21896645, FT ECO:0000269|PubMed:23166352" FT /id="VAR_024019" FT VARIANT 122 FT /note="L -> V (in CMT1C; dbSNP:rs104894522)" FT /evidence="ECO:0000269|PubMed:15776429" FT /id="VAR_024020" FT MUTAGEN 17..20 FT /note="PSAP->ASAA: Impaired function in targeting FT endocytosed proteins for lysosomal degradation." FT /evidence="ECO:0000269|PubMed:23166352" FT MUTAGEN 17..19 FT /note="PSA->AGG: Abolishes interaction with TSG101." FT /evidence="ECO:0000269|PubMed:16118794" FT MUTAGEN 23 FT /note="Y->A: Abolishes interaction with NEDD4." FT /evidence="ECO:0000269|PubMed:16118794" FT MUTAGEN 23 FT /note="Y->A: Abolishes interaction with WWOX. Abolishes FT interaction with NEDD4. Abolishes interaction with NEDD4 FT and impairs location at endosomes; when associated with FT A-61." FT /evidence="ECO:0000269|PubMed:15064722, FT ECO:0000269|PubMed:27927196" FT MUTAGEN 61 FT /note="Y->A: No effect on interaction with WWOX. No effect FT on interaction with NEDD4. Abolishes interaction with NEDD4 FT and impairs location at endosomes; when associated with FT A-23." FT /evidence="ECO:0000269|PubMed:15064722, FT ECO:0000269|PubMed:27927196" FT MUTAGEN 96 FT /note="C->A: Abolishes association with cytoplasmic vesicle FT membranes." FT /evidence="ECO:0000269|PubMed:27582497" FT MUTAGEN 135 FT /note="P->T: Decreases protein stability and association FT with early endosome membranes. Impaired function in FT targeting endocytosed proteins for lysosomal degradation." FT /evidence="ECO:0000269|PubMed:21896645, FT ECO:0000269|PubMed:23166352" FT MUTAGEN 144 FT /note="V->M: No effect on location at endosomes, but FT impairs protein stability." FT /evidence="ECO:0000269|PubMed:27927196" FT MUTAGEN 148 FT /note="C->A: Abolishes association with cytoplasmic vesicle FT membranes." FT /evidence="ECO:0000269|PubMed:27582497" FT VARIANT Q99732-2:174 FT /note="A -> S (found as a somatic mutation in a EMPD FT primary tumor)" FT /evidence="ECO:0000305" FT /id="VAR_082859" SQ SEQUENCE 161 AA; 17107 MW; 08D15BF1FDCA16F0 CRC64; MSVPGPYQAA TGPSSAPSAP PSYEETVAVN SYYPTPPAPM PGPTTGLVTG PDGKGMNPPS YYTQPAPIPN NNPITVQTVY VQHPITFLDR PIQMCCPSCN KMIVSQLSYN AGALTWLSCG SLCLLGCIAG CCFIPFCVDA LQDVDHYCPN CRALLGTYKR L //