TFIP8_HUMAN
ID TFIP8_HUMAN Reviewed; 198 AA.
AC O95379; B3KMH1; B3KMI2; B7Z713; Q9P1Q1; Q9UER5; Q9UP47;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Tumor necrosis factor alpha-induced protein 8;
DE Short=TNF alpha-induced protein 8;
DE AltName: Full=Head and neck tumor and metastasis-related protein;
DE AltName: Full=MDC-3.13;
DE AltName: Full=NF-kappa-B-inducible DED-containing protein;
DE Short=NDED;
DE AltName: Full=SCC-S2;
DE AltName: Full=TNF-induced protein GG2-1;
GN Name=TNFAIP8;
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 3), AND TISSUE SPECIFICITY.
RC TISSUE=Umbilical vein;
RX PubMed=10233894;
RA Horrevoets A.J.G., Fontijn R.D., van Zonneveld A.J., de Vries C.J.M.,
RA ten Cate J.W., Pannekoek H.;
RT "Vascular endothelial genes that are responsive to tumor necrosis factor-
RT alpha in vitro are expressed in atherosclerotic lesions, including
RT inhibitor of apoptosis protein-1, stannin, and two novel genes.";
RL Blood 93:3418-3431(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Nietfeld W., Meyerhans A.F.;
RT "Identification of cellular factors involved in the differentiation of
RT dendritic cells.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Placenta;
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 GENOMIC DNA].
RC TISSUE=Stomach;
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Urinary bladder;
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 [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 99-198 (ISOFORM 3), IDENTIFICATION, FUNCTION,
RP INDUCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Heart;
RX PubMed=10644768; DOI=10.1074/jbc.275.4.2973;
RA Kumar D., Whiteside T.L., Kasid U.;
RT "Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-
RT S2, containing the consensus sequence of a death effector domain of fas-
RT associated death domain-like interleukin-1beta-converting enzyme-inhibitory
RT protein.";
RL J. Biol. Chem. 275:2973-2978(2000).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=11346652; DOI=10.1074/jbc.m102464200;
RA You Z., Ouyang H., Lopatin D., Polver P.J., Wang C.-Y.;
RT "Nuclear factor-kappa B-inducible death effector domain-containing protein
RT suppresses tumor necrosis factor-mediated apoptosis by inhibiting caspase-8
RT activity.";
RL J. Biol. Chem. 276:26398-26404(2001).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=14724590; DOI=10.1038/sj.onc.1207123;
RA Kumar D., Gokhale P., Broustas C., Chakravarty D., Ahmad I., Kasid U.;
RT "Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced
RT proliferation and tumorigenicity of MDA-MB 435 cells.";
RL Oncogene 23:612-616(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Acts as a negative mediator of apoptosis and may play a role
CC in tumor progression. Suppresses the TNF-mediated apoptosis by
CC inhibiting caspase-8 activity but not the processing of procaspase-8,
CC subsequently resulting in inhibition of BID cleavage and caspase-3
CC activation. {ECO:0000269|PubMed:10644768, ECO:0000269|PubMed:11346652,
CC ECO:0000269|PubMed:14724590}.
CC -!- INTERACTION:
CC O95379; Q86V38: ATN1; NbExp=3; IntAct=EBI-1049336, EBI-11954292;
CC O95379; Q96JC9: EAF1; NbExp=3; IntAct=EBI-1049336, EBI-769261;
CC O95379; Q56P03: EAPP; NbExp=3; IntAct=EBI-1049336, EBI-748732;
CC O95379; Q8NBZ0: INO80E; NbExp=3; IntAct=EBI-1049336, EBI-769401;
CC O95379; Q9NPJ6: MED4; NbExp=7; IntAct=EBI-1049336, EBI-394607;
CC O95379; Q96S99: PLEKHF1; NbExp=3; IntAct=EBI-1049336, EBI-745767;
CC O95379; Q9H8W4: PLEKHF2; NbExp=4; IntAct=EBI-1049336, EBI-742388;
CC O95379; Q9NZ81: PRR13; NbExp=6; IntAct=EBI-1049336, EBI-740924;
CC O95379; O00560: SDCBP; NbExp=6; IntAct=EBI-1049336, EBI-727004;
CC O95379; Q96CG3: TIFA; NbExp=3; IntAct=EBI-1049336, EBI-740711;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14724590}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O95379-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95379-2; Sequence=VSP_024899;
CC Name=3;
CC IsoId=O95379-3; Sequence=VSP_024898;
CC Name=4;
CC IsoId=O95379-4; Sequence=VSP_054827;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the spleen, lymph node,
CC thymus, thyroid, bone marrow and placenta. Expressed at high levels
CC both in various tumor tissues, unstimulated and cytokine-activated
CC cultured cells. Expressed at low levels in the spinal cord, ovary,
CC lung, adrenal glands, heart, brain, testis and skeletal muscle.
CC {ECO:0000269|PubMed:10233894, ECO:0000269|PubMed:10644768,
CC ECO:0000269|PubMed:14724590}.
CC -!- DEVELOPMENTAL STAGE: Expressed at high levels in the fetal liver, lung
CC and kidney. {ECO:0000269|PubMed:10644768}.
CC -!- INDUCTION: By nuclear factor-KB (NF-KB) and TNF. Induction by TNF
CC depends upon activation of NF-KB. {ECO:0000269|PubMed:10644768,
CC ECO:0000269|PubMed:11346652}.
CC -!- SIMILARITY: Belongs to the TNFAIP8 family. {ECO:0000305}.
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DR EMBL; AF070671; AAC83229.1; -; mRNA.
DR EMBL; AF099935; AAC72975.1; -; mRNA.
DR EMBL; AF099936; AAC72976.1; -; mRNA.
DR EMBL; CR457137; CAG33418.1; -; mRNA.
DR EMBL; AK001850; BAG50983.1; -; mRNA.
DR EMBL; AK001931; BAG50994.1; -; mRNA.
DR EMBL; AK301281; BAH13449.1; -; mRNA.
DR EMBL; AC008475; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC027320; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC035144; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471086; EAW48914.1; -; Genomic_DNA.
DR EMBL; BC005352; AAH05352.1; -; mRNA.
DR EMBL; BC007014; AAH07014.1; -; mRNA.
DR EMBL; AF098933; AAF29435.1; -; mRNA.
DR CCDS; CCDS47257.1; -. [O95379-3]
DR CCDS; CCDS47258.1; -. [O95379-1]
DR CCDS; CCDS68933.1; -. [O95379-4]
DR RefSeq; NP_001071122.1; NM_001077654.2. [O95379-3]
DR RefSeq; NP_001273742.1; NM_001286813.1. [O95379-1]
DR RefSeq; NP_001273743.1; NM_001286814.1. [O95379-4]
DR RefSeq; NP_001273744.1; NM_001286815.1.
DR RefSeq; NP_001273746.1; NM_001286817.1.
DR RefSeq; NP_055165.2; NM_014350.3. [O95379-1]
DR AlphaFoldDB; O95379; -.
DR SMR; O95379; -.
DR BioGRID; 117344; 31.
DR IntAct; O95379; 14.
DR MINT; O95379; -.
DR STRING; 9606.ENSP00000427424; -.
DR iPTMnet; O95379; -.
DR PhosphoSitePlus; O95379; -.
DR BioMuta; TNFAIP8; -.
DR EPD; O95379; -.
DR jPOST; O95379; -.
DR MassIVE; O95379; -.
DR MaxQB; O95379; -.
DR PaxDb; O95379; -.
DR PeptideAtlas; O95379; -.
DR PRIDE; O95379; -.
DR ProteomicsDB; 50831; -. [O95379-1]
DR ProteomicsDB; 50832; -. [O95379-2]
DR ProteomicsDB; 50833; -. [O95379-3]
DR ProteomicsDB; 6823; -.
DR Antibodypedia; 25539; 268 antibodies from 32 providers.
DR DNASU; 25816; -.
DR Ensembl; ENST00000274456.6; ENSP00000274456.6; ENSG00000145779.8. [O95379-3]
DR Ensembl; ENST00000503646.1; ENSP00000421848.1; ENSG00000145779.8. [O95379-1]
DR Ensembl; ENST00000504771.3; ENSP00000422245.1; ENSG00000145779.8. [O95379-1]
DR Ensembl; ENST00000513374.1; ENSP00000427424.1; ENSG00000145779.8. [O95379-4]
DR GeneID; 25816; -.
DR KEGG; hsa:25816; -.
DR MANE-Select; ENST00000504771.3; ENSP00000422245.1; NM_014350.4; NP_055165.2.
DR UCSC; uc003ksg.5; human. [O95379-1]
DR CTD; 25816; -.
DR DisGeNET; 25816; -.
DR GeneCards; TNFAIP8; -.
DR HGNC; HGNC:17260; TNFAIP8.
DR HPA; ENSG00000145779; Tissue enhanced (lymphoid).
DR MIM; 612111; gene.
DR neXtProt; NX_O95379; -.
DR OpenTargets; ENSG00000145779; -.
DR PharmGKB; PA134957136; -.
DR VEuPathDB; HostDB:ENSG00000145779; -.
DR eggNOG; ENOG502S00N; Eukaryota.
DR GeneTree; ENSGT00390000003488; -.
DR HOGENOM; CLU_085918_1_0_1; -.
DR InParanoid; O95379; -.
DR OMA; FYELEFS; -.
DR OrthoDB; 1284744at2759; -.
DR PhylomeDB; O95379; -.
DR TreeFam; TF323415; -.
DR PathwayCommons; O95379; -.
DR Reactome; R-HSA-1483255; PI Metabolism.
DR SignaLink; O95379; -.
DR SIGNOR; O95379; -.
DR BioGRID-ORCS; 25816; 9 hits in 1077 CRISPR screens.
DR ChiTaRS; TNFAIP8; human.
DR GeneWiki; TNFAIP8; -.
DR GenomeRNAi; 25816; -.
DR Pharos; O95379; Tbio.
DR PRO; PR:O95379; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O95379; protein.
DR Bgee; ENSG00000145779; Expressed in cartilage tissue and 172 other tissues.
DR ExpressionAtlas; O95379; baseline and differential.
DR Genevisible; O95379; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR Gene3D; 1.20.1440.160; -; 1.
DR InterPro; IPR008477; TNFAIP8-like.
DR InterPro; IPR038355; TNFAIP8_sf.
DR PANTHER; PTHR12757; PTHR12757; 1.
DR Pfam; PF05527; DUF758; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Coiled coil; Cytoplasm;
KW Reference proteome.
FT CHAIN 1..198
FT /note="Tumor necrosis factor alpha-induced protein 8"
FT /id="PRO_0000285718"
FT COILED 49..83
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..11
FT /note="MHSEAEESKEV -> M (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10233894,
FT ECO:0000303|PubMed:10644768, ECO:0000303|PubMed:14702039"
FT /id="VSP_024898"
FT VAR_SEQ 1..10
FT /note="MHSEAEESKE -> MA (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2, ECO:0000303|Ref.3"
FT /id="VSP_024899"
FT VAR_SEQ 1..10
FT /note="MHSEAEESKE -> MTLPRYCEVVLLIAHGEKMLKL (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054827"
FT VARIANT 151
FT /note="S -> C (in dbSNP:rs3203922)"
FT /id="VAR_032047"
SQ SEQUENCE 198 AA; 23003 MW; D9B8F6FCF9AFC2C3 CRC64;
MHSEAEESKE VATDVFNSKN LAVQAQKKIL GKMVSKSIAT TLIDDTSSEV LDELYRVTRE
YTQNKKEAEK IIKNLIKTVI KLAILYRNNQ FNQDELALME KFKKKVHQLA MTVVSFHQVD
YTFDRNVLSR LLNECREMLH QIIQRHLTAK SHGRVNNVFD HFSDCEFLAA LYNPFGNFKP
HLQKLCDGIN KMLDEENI
