TNIP2_HUMAN
ID TNIP2_HUMAN Reviewed; 429 AA.
AC Q8NFZ5; B1AKS4; B3KTY8; D3DVQ9; Q7L5L2; Q9BQR6; Q9H682;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=TNFAIP3-interacting protein 2;
DE AltName: Full=A20-binding inhibitor of NF-kappa-B activation 2;
DE Short=ABIN-2;
DE AltName: Full=Fetal liver LKB1-interacting protein;
GN Name=TNIP2 {ECO:0000312|EMBL:EAW82514.1};
GN Synonyms=ABIN2, FLIP1 {ECO:0000312|EMBL:AAM21315.1};
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] {ECO:0000305, ECO:0000312|EMBL:CAC34835.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11390377; DOI=10.1074/jbc.m100048200;
RA Van Huffel S.C., Delaei F., Heyninck K., De Valck D., Beyaert R.;
RT "Identification of a novel A20-binding inhibitor of nuclear factor-kappaB
RT activation termed ABIN-2.";
RL J. Biol. Chem. 276:30216-30223(2001).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAM21315.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND INTERACTION WITH STK11/LKB1.
RX PubMed=12595760; DOI=10.1007/bf02256059;
RA Liu W.-K., Chien C.-Y., Chou C.-K., Su J.-Y.;
RT "An LKB1-interacting protein negatively regulates TNFalpha-induced NF-
RT kappaB activation.";
RL J. Biomed. Sci. 10:242-252(2003).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAB15382.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP VAL-396.
RC TISSUE=Kidney epithelium {ECO:0000312|EMBL:BAB15382.1};
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 [4] {ECO:0000305, ECO:0000312|EMBL:EAW82514.1}
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6] {ECO:0000305, ECO:0000312|EMBL:AAH02740.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-396.
RC TISSUE=Uterus {ECO:0000312|EMBL:AAH02740.2};
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 [7]
RP INTERACTION WITH TNFAIP3.
RX PubMed=11389905; DOI=10.1016/s0014-5793(01)02504-2;
RA Klinkenberg M., Van Huffel S., Heyninck K., Beyaert R.;
RT "Functional redundancy of the zinc fingers of A20 for inhibition of NF-
RT kappaB activation and protein-protein interactions.";
RL FEBS Lett. 498:93-97(2001).
RN [8]
RP FUNCTION.
RX PubMed=12933576; DOI=10.1182/blood-2003-05-1602;
RA Tadros A., Hughes D.P., Dunmore B.J., Brindle N.P.;
RT "ABIN-2 protects endothelial cells from death and has a role in the
RT antiapoptotic effect of angiopoietin-1.";
RL Blood 102:4407-4409(2003).
RN [9]
RP INTERACTION WITH TEK.
RX PubMed=12609966; DOI=10.1161/01.res.0000063422.38690.dc;
RA Hughes D.P., Marron M.B., Brindle N.P.;
RT "The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a
RT novel nuclear factor-kappaB inhibitor ABIN-2.";
RL Circ. Res. 92:630-636(2003).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SMARCD1.
RX PubMed=12753905; DOI=10.1016/s0014-5793(03)00401-0;
RA Chien C.Y., Liu W.K., Chou C.K., Su J.Y.;
RT "The A20-binding protein ABIN-2 exerts unexpected function in mediating
RT transcriptional coactivation.";
RL FEBS Lett. 543:55-60(2003).
RN [11] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH IKBKG.
RX PubMed=14653779; DOI=10.1042/bj20031736;
RA Liu W.-K., Yen P.-F., Chien C.-Y., Fann M.-J., Su J.-Y., Chou C.-K.;
RT "The inhibitor ABIN-2 disrupts the interaction of receptor-interacting
RT protein with the kinase subunit IKKgamma to block activation of the
RT transcription factor NF-kappaB and potentiate apoptosis.";
RL Biochem. J. 378:867-876(2004).
RN [12] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH NFKB1; MAP3K8 AND TNFAIP3.
RX PubMed=15169888; DOI=10.1128/mcb.24.12.5235-5248.2004;
RA Lang V., Symons A., Watton S.J., Janzen J., Soneji Y., Beinke S.,
RA Howell S., Ley S.C.;
RT "ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is
RT essential for TPL-2 protein stability.";
RL Mol. Cell. Biol. 24:5235-5248(2004).
RN [13]
RP UBIQUITIN-BINDING, AND MUTAGENESIS OF 309-ASP-PHE-310 AND 313-GLU-ARG-314.
RX PubMed=18212736; DOI=10.1038/sj.onc.1211042;
RA Wagner S., Carpentier I., Rogov V., Kreike M., Ikeda F., Lohr F., Wu C.J.,
RA Ashwell J.D., Dotsch V., Dikic I., Beyaert R.;
RT "Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN
RT proteins.";
RL Oncogene 27:3739-3745(2008).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CHUK AND IKBKB,
RP UBIQUITINATION, PHOSPHORYLATION, AND MUTAGENESIS OF SER-62 AND SER-146.
RX PubMed=21784860; DOI=10.1074/jbc.m111.236448;
RA Leotoing L., Chereau F., Baron S., Hube F., Valencia H.J., Bordereaux D.,
RA Demmers J.A., Strouboulis J., Baud V.;
RT "A20-binding inhibitor of nuclear factor-kappaB (NF-kappaB)-2 (ABIN-2) is
RT an activator of inhibitor of NF-kappaB (IkappaB) kinase alpha (IKKalpha)-
RT mediated NF-kappaB transcriptional activity.";
RL J. Biol. Chem. 286:32277-32288(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP INTERACTION WITH SFTSV VIRUS NSS (MICROBIAL INFECTION).
RX PubMed=30617349; DOI=10.1038/s41564-018-0329-x;
RA Choi Y., Park S.J., Sun Y., Yoo J.S., Pudupakam R.S., Foo S.S., Shin W.J.,
RA Chen S.B., Tsichlis P.N., Lee W.J., Lee J.S., Li W., Brennan B., Choi Y.K.,
RA Jung J.U.;
RT "Severe fever with thrombocytopenia syndrome phlebovirus non-structural
RT protein activates TPL2 signalling pathway for viral immunopathogenesis.";
RL Nat. Microbiol. 4:429-437(2019).
RN [18]
RP VARIANTS HIS-249 AND LYS-255, INTERACTION WITH TNFAIP3, AND
RP CHARACTERIZATION OF VARIANT LYS-255.
RX PubMed=21266526; DOI=10.1158/1078-0432.ccr-10-1859;
RA Dong G., Chanudet E., Zeng N., Appert A., Chen Y.W., Au W.Y., Hamoudi R.A.,
RA Watkins A.J., Ye H., Liu H., Gao Z., Chuang S.S., Srivastava G., Du M.Q.;
RT "A20, ABIN-1/2, and CARD11 mutations and their prognostic value in
RT gastrointestinal diffuse large B-cell lymphoma.";
RL Clin. Cancer Res. 17:1440-1451(2011).
CC -!- FUNCTION: Inhibits NF-kappa-B activation by blocking the interaction of
CC RIPK1 with its downstream effector NEMO/IKBKG. Forms a ternary complex
CC with NFKB1 and MAP3K8 but appears to function upstream of MAP3K8 in the
CC TLR4 signaling pathway that regulates MAP3K8 activation. Involved in
CC activation of the MEK/ERK signaling pathway during innate immune
CC response; this function seems to be stimulus- and cell type specific.
CC Required for stability of MAP3K8. Involved in regulation of apoptosis
CC in endothelial cells; promotes TEK agonist-stimulated endothelial
CC survival. May act as transcriptional coactivator when translocated to
CC the nucleus. Enhances CHUK-mediated NF-kappa-B activation involving NF-
CC kappa-B p50-p65 and p50-c-Rel complexes. {ECO:0000269|PubMed:12595760,
CC ECO:0000269|PubMed:12753905, ECO:0000269|PubMed:12933576,
CC ECO:0000269|PubMed:14653779, ECO:0000269|PubMed:15169888,
CC ECO:0000269|PubMed:21784860}.
CC -!- SUBUNIT: Interacts with STK11/LKB1, TNFAIP3, IKBKG, NFKB1, MAP3K8, TEK,
CC RIPK1, CHUK, IKBKB and SMARCD1. Interacts with polyubiquitin.
CC {ECO:0000269|PubMed:11389905, ECO:0000269|PubMed:12595760,
CC ECO:0000269|PubMed:12609966, ECO:0000269|PubMed:12753905,
CC ECO:0000269|PubMed:14653779, ECO:0000269|PubMed:15169888,
CC ECO:0000269|PubMed:21266526, ECO:0000269|PubMed:21784860}.
CC -!- SUBUNIT: (Microbial infection) Interacts with severe fever with
CC thrombocytopenia syndrome virus (SFTSV) NSs; this interaction promotes
CC TPL2 complex formation and signaling activity leading to IL-10
CC production. {ECO:0000269|PubMed:30617349}.
CC -!- INTERACTION:
CC Q8NFZ5; Q9Y6K9: IKBKG; NbExp=8; IntAct=EBI-359372, EBI-81279;
CC Q8NFZ5; P41279: MAP3K8; NbExp=10; IntAct=EBI-359372, EBI-354900;
CC Q8NFZ5; P19838: NFKB1; NbExp=7; IntAct=EBI-359372, EBI-300010;
CC Q8NFZ5; P19838-1: NFKB1; NbExp=8; IntAct=EBI-359372, EBI-1452239;
CC Q8NFZ5; Q04864: REL; NbExp=2; IntAct=EBI-359372, EBI-307352;
CC Q8NFZ5; Q15831: STK11; NbExp=5; IntAct=EBI-359372, EBI-306838;
CC Q8NFZ5; P21580: TNFAIP3; NbExp=4; IntAct=EBI-359372, EBI-527670;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12595760}. Nucleus
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:11390377, ECO:0000269|PubMed:12595760,
CC ECO:0000269|PubMed:15489334};
CC IsoId=Q8NFZ5-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:14702039};
CC IsoId=Q8NFZ5-2; Sequence=VSP_052701;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues examined.
CC {ECO:0000269|PubMed:12595760}.
CC -!- PTM: In vitro phosphorylated by CHUK. {ECO:0000269|PubMed:21784860}.
CC -!- PTM: Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination
CC probably leading to constitutive proteasomal degradation which can be
CC impaired by IKK-A/CHUK or IKBKB probably involving deubiquitination.
CC {ECO:0000269|PubMed:21784860}.
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DR EMBL; AJ304866; CAC34835.1; -; mRNA.
DR EMBL; AF372839; AAM21315.1; -; mRNA.
DR EMBL; AK026176; BAB15382.1; -; mRNA.
DR EMBL; AK096296; BAG53250.1; -; mRNA.
DR EMBL; CH471131; EAW82514.1; -; Genomic_DNA.
DR EMBL; AL121750; CAM28233.1; -; Genomic_DNA.
DR EMBL; AL110117; CAM28233.1; JOINED; Genomic_DNA.
DR EMBL; CH471131; EAW82516.1; -; Genomic_DNA.
DR EMBL; BC002740; AAH02740.2; -; mRNA.
DR CCDS; CCDS3362.1; -. [Q8NFZ5-1]
DR CCDS; CCDS54714.1; -. [Q8NFZ5-2]
DR RefSeq; NP_001154999.1; NM_001161527.1. [Q8NFZ5-2]
DR RefSeq; NP_001278945.1; NM_001292016.1.
DR RefSeq; NP_077285.3; NM_024309.3. [Q8NFZ5-1]
DR PDB; 5H07; X-ray; 2.59 A; C/D=257-344.
DR PDBsum; 5H07; -.
DR AlphaFoldDB; Q8NFZ5; -.
DR SMR; Q8NFZ5; -.
DR BioGRID; 122573; 950.
DR CORUM; Q8NFZ5; -.
DR DIP; DIP-27617N; -.
DR IntAct; Q8NFZ5; 94.
DR MINT; Q8NFZ5; -.
DR STRING; 9606.ENSP00000321203; -.
DR iPTMnet; Q8NFZ5; -.
DR PhosphoSitePlus; Q8NFZ5; -.
DR BioMuta; TNIP2; -.
DR DMDM; 74715616; -.
DR EPD; Q8NFZ5; -.
DR jPOST; Q8NFZ5; -.
DR MassIVE; Q8NFZ5; -.
DR MaxQB; Q8NFZ5; -.
DR PaxDb; Q8NFZ5; -.
DR PeptideAtlas; Q8NFZ5; -.
DR PRIDE; Q8NFZ5; -.
DR ProteomicsDB; 73398; -. [Q8NFZ5-1]
DR ProteomicsDB; 73399; -. [Q8NFZ5-2]
DR Antibodypedia; 22391; 230 antibodies from 27 providers.
DR DNASU; 79155; -.
DR Ensembl; ENST00000315423.12; ENSP00000321203.7; ENSG00000168884.15. [Q8NFZ5-1]
DR Ensembl; ENST00000510267.5; ENSP00000427613.1; ENSG00000168884.15. [Q8NFZ5-2]
DR GeneID; 79155; -.
DR KEGG; hsa:79155; -.
DR MANE-Select; ENST00000315423.12; ENSP00000321203.7; NM_024309.4; NP_077285.3.
DR UCSC; uc003gff.3; human. [Q8NFZ5-1]
DR CTD; 79155; -.
DR DisGeNET; 79155; -.
DR GeneCards; TNIP2; -.
DR HGNC; HGNC:19118; TNIP2.
DR HPA; ENSG00000168884; Low tissue specificity.
DR MIM; 610669; gene.
DR neXtProt; NX_Q8NFZ5; -.
DR OpenTargets; ENSG00000168884; -.
DR PharmGKB; PA134957006; -.
DR VEuPathDB; HostDB:ENSG00000168884; -.
DR eggNOG; ENOG502QUCD; Eukaryota.
DR GeneTree; ENSGT00510000046908; -.
DR HOGENOM; CLU_039735_1_0_1; -.
DR InParanoid; Q8NFZ5; -.
DR OMA; LRCPHCM; -.
DR OrthoDB; 882290at2759; -.
DR PhylomeDB; Q8NFZ5; -.
DR TreeFam; TF332167; -.
DR PathwayCommons; Q8NFZ5; -.
DR Reactome; R-HSA-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR SignaLink; Q8NFZ5; -.
DR SIGNOR; Q8NFZ5; -.
DR BioGRID-ORCS; 79155; 18 hits in 1089 CRISPR screens.
DR ChiTaRS; TNIP2; human.
DR GeneWiki; TNIP2; -.
DR GenomeRNAi; 79155; -.
DR Pharos; Q8NFZ5; Tbio.
DR PRO; PR:Q8NFZ5; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8NFZ5; protein.
DR Bgee; ENSG00000168884; Expressed in tendon of biceps brachii and 199 other tissues.
DR ExpressionAtlas; Q8NFZ5; baseline and differential.
DR Genevisible; Q8NFZ5; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0023035; P:CD40 signaling pathway; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0050871; P:positive regulation of B cell activation; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0043032; P:positive regulation of macrophage activation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR InterPro; IPR022008; EABR.
DR InterPro; IPR034735; NEMO_ZF.
DR Pfam; PF12180; EABR; 1.
DR PROSITE; PS51801; ZF_CCHC_NOA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Coiled coil; Cytoplasm;
KW Host-virus interaction; Inflammatory response; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..429
FT /note="TNFAIP3-interacting protein 2"
FT /id="PRO_0000322583"
FT ZN_FING 397..429
FT /note="CCHC NOA-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT REGION 177..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..347
FT /note="Ubiquitin-binding domain (UBD)"
FT REGION 372..400
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 29..117
FT /evidence="ECO:0000255"
FT COILED 196..226
FT /evidence="ECO:0000255"
FT COILED 255..340
FT /evidence="ECO:0000255"
FT COMPBIAS 177..192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 405
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 408
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 423
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 427
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..107
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_052701"
FT VARIANT 249
FT /note="Q -> H (found in patients with gastrointestinal
FT diffuse large cell lymphoma; impairs inhibitory activity on
FT CARD11-induced NF-kappa-B activation; dbSNP:rs116129895)"
FT /evidence="ECO:0000269|PubMed:21266526"
FT /id="VAR_067969"
FT VARIANT 255
FT /note="E -> K (found in patients with gastrointestinal
FT diffuse large cell lymphoma; somatic mutation; impairs
FT inhibitory activity on CARD11-induced NF-kappa-B activation
FT and impairs interaction with TNFAIP3; dbSNP:rs116412781)"
FT /evidence="ECO:0000269|PubMed:21266526"
FT /id="VAR_067970"
FT VARIANT 396
FT /note="A -> V (in dbSNP:rs2269495)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_039463"
FT MUTAGEN 62
FT /note="S->A: Reduces phosphorylation."
FT /evidence="ECO:0000269|PubMed:21784860"
FT MUTAGEN 146
FT /note="S->A: Reduces phosphorylation; reduces CHUK-mediated
FT NF-kappa-B activation."
FT /evidence="ECO:0000269|PubMed:21784860"
FT MUTAGEN 309..310
FT /note="DF->NA: Abolishes ubiquitin binding."
FT /evidence="ECO:0000269|PubMed:18212736"
FT MUTAGEN 313..314
FT /note="ER->AA: Abolishes ubiquitin binding; loss of
FT inhibitory activity on NF-kappa-B activation."
FT /evidence="ECO:0000269|PubMed:18212736"
FT CONFLICT 153
FT /note="Q -> H (in Ref. 1; CAC34835)"
FT /evidence="ECO:0000305"
FT HELIX 263..273
FT /evidence="ECO:0007829|PDB:5H07"
FT HELIX 276..336
FT /evidence="ECO:0007829|PDB:5H07"
SQ SEQUENCE 429 AA; 48700 MW; 0F6B049C2B3483DC CRC64;
MSRDPGSGGW EEAPRAAAAL CTLYHEAGQR LRRLQDQLAA RDALIARLRA RLAALEGDAA
PSLVDALLEQ VARFREQLRR QEGGAAEAQM RQEIERLTER LEEKEREMQQ LLSQPQHERE
KEVVLLRRSM AEGERARAAS DVLCRSLANE THQLRRTLTA TAHMCQHLAK CLDERQHAQR
NVGERSPDQS EHTDGHTSVQ SVIEKLQEEN RLLKQKVTHV EDLNAKWQRY NASRDEYVRG
LHAQLRGLQI PHEPELMRKE ISRLNRQLEE KINDCAEVKQ ELAASRTARD AALERVQMLE
QQILAYKDDF MSERADRERA QSRIQELEEK VASLLHQVSW RQDSREPDAG RIHAGSKTAK
YLAADALELM VPGGWRPGTG SQQPEPPAEG GHPGAAQRGQ GDLQCPHCLQ CFSDEQGEEL
LRHVAECCQ
