TNIP2_MOUSE
ID TNIP2_MOUSE Reviewed; 430 AA.
AC Q99JG7; Q3TVF3;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=TNFAIP3-interacting protein 2;
DE AltName: Full=A20-binding inhibitor of NF-kappa-B activation 2;
DE Short=ABIN-2;
GN Name=Tnip2 {ECO:0000312|MGI:MGI:2386643}; Synonyms=Abin2;
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] {ECO:0000305, ECO:0000312|EMBL:CAC34841.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND INTERACTION
RP WITH TNFAIP3.
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:0000312|EMBL:BAE35666.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE35666.1};
RC TISSUE=Pancreas {ECO:0000312|EMBL:BAE35666.1};
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 [3]
RP FUNCTION.
RX PubMed=16633345; DOI=10.1038/ni1334;
RA Papoutsopoulou S., Symons A., Tharmalingham T., Belich M.P., Kaiser F.,
RA Kioussis D., O'Garra A., Tybulewicz V., Ley S.C.;
RT "ABIN-2 is required for optimal activation of Erk MAP kinase in innate
RT immune responses.";
RL Nat. Immunol. 7:606-615(2006).
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:11390377,
CC ECO:0000269|PubMed:16633345}.
CC -!- SUBUNIT: Interacts with STK11/LKB1, TNFAIP3, IKBKG, NFKB1, MAP3K8, TEK,
CC RIPK1, CHUK, IKBKB and SMARCD1. Interacts with polyubiquitin (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8NFZ5}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in all tissues examined.
CC {ECO:0000269|PubMed:11390377}.
CC -!- PTM: In vitro phosphorylated by CHUK. {ECO:0000250}.
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:0000250}.
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DR EMBL; AJ304865; CAC34841.1; -; mRNA.
DR EMBL; AK160165; BAE35666.1; -; mRNA.
DR CCDS; CCDS19214.1; -.
DR RefSeq; NP_620703.1; NM_139064.2.
DR AlphaFoldDB; Q99JG7; -.
DR SMR; Q99JG7; -.
DR BioGRID; 231088; 4.
DR IntAct; Q99JG7; 2.
DR STRING; 10090.ENSMUSP00000085030; -.
DR iPTMnet; Q99JG7; -.
DR PhosphoSitePlus; Q99JG7; -.
DR EPD; Q99JG7; -.
DR MaxQB; Q99JG7; -.
DR PaxDb; Q99JG7; -.
DR PRIDE; Q99JG7; -.
DR ProteomicsDB; 259141; -.
DR Antibodypedia; 22391; 230 antibodies from 27 providers.
DR Ensembl; ENSMUST00000087737; ENSMUSP00000085030; ENSMUSG00000059866.
DR GeneID; 231130; -.
DR KEGG; mmu:231130; -.
DR UCSC; uc008xcj.1; mouse.
DR CTD; 79155; -.
DR MGI; MGI:2386643; Tnip2.
DR VEuPathDB; HostDB:ENSMUSG00000059866; -.
DR eggNOG; ENOG502QUCD; Eukaryota.
DR GeneTree; ENSGT00510000046908; -.
DR HOGENOM; CLU_039735_0_1_1; -.
DR InParanoid; Q99JG7; -.
DR OMA; LRCPHCM; -.
DR OrthoDB; 882290at2759; -.
DR PhylomeDB; Q99JG7; -.
DR TreeFam; TF332167; -.
DR Reactome; R-MMU-5684264; MAP3K8 (TPL2)-dependent MAPK1/3 activation.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR BioGRID-ORCS; 231130; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Tnip2; mouse.
DR PRO; PR:Q99JG7; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q99JG7; protein.
DR Bgee; ENSMUSG00000059866; Expressed in retinal neural layer and 158 other tissues.
DR ExpressionAtlas; Q99JG7; baseline and differential.
DR Genevisible; Q99JG7; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0023035; P:CD40 signaling pathway; IMP:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0050871; P:positive regulation of B cell activation; IMP:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP: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; IMP:UniProtKB.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; IMP:UniProtKB.
DR InterPro; IPR032419; CC2-LZ_dom.
DR InterPro; IPR022008; EABR.
DR InterPro; IPR034735; NEMO_ZF.
DR Pfam; PF16516; CC2-LZ; 1.
DR Pfam; PF12180; EABR; 1.
DR PROSITE; PS51801; ZF_CCHC_NOA; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Coiled coil; Cytoplasm; Inflammatory response; Metal-binding;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..430
FT /note="TNFAIP3-interacting protein 2"
FT /id="PRO_0000322584"
FT ZN_FING 398..430
FT /note="CCHC NOA-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT REGION 183..202
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..348
FT /note="Ubiquitin-binding domain (UBD)"
FT REGION 373..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 30..139
FT /evidence="ECO:0000255"
FT COILED 198..227
FT /evidence="ECO:0000255"
FT COILED 256..344
FT /evidence="ECO:0000255"
FT BINDING 406
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 409
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 424
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT BINDING 428
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01142"
FT MOD_RES 8
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NFZ5"
FT CONFLICT 164
FT /note="H -> N (in Ref. 2; BAE35666)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 430 AA; 49094 MW; 35F533967072512D CRC64;
MSSGDPRSGR QDGAPRAAAA LCGLYHEAGQ QLQRLKDQLA ARDALIASLR TRLAALEGHT
APSLVDALLD QVERFREQLR RQEEGASETQ LRQEVERLTE RLEEKEREMQ QLMSQPQHEQ
EKEVVLLRRS VAEKEKARAA SDVLCRSLAD ETHQLRRTLA ATAHMCQHLA KCLDERQCAQ
GDAGEKSPAE LEQTSSDASG QSVIKKLQEE NRLLKQKVTH VEDLNAKWQR YDASRDEYVK
GLHAQLKRRQ VPLEPELMKK EISRLNRQLE EKISDCAEAN QELTAMRMSR DTALERVQML
EQQILAYKDD FKSERADRER AHSRIQELEE KIMSLMYQVS QRQDSREPGP CRIHTGNKTA
KYLEMDALEH VTPGGWRPES RSQQMEPSAE GGHVCTAQRG QGDLQCPHCL RCFSDEQGEA
FLRHLSECCQ
