TNIP1_MOUSE
ID TNIP1_MOUSE Reviewed; 647 AA.
AC Q9WUU8; Q922A9; Q922F7; Q9EPP8; Q9R0X3;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=TNFAIP3-interacting protein 1;
DE AltName: Full=A20-binding inhibitor of NF-kappa-B activation 1;
DE Short=ABIN;
DE Short=ABIN-1;
DE AltName: Full=Nef-associated factor 1;
DE Short=Naf1;
DE AltName: Full=Virion-associated nuclear shuttling protein;
DE Short=VAN;
DE Short=mVAN;
GN Name=Tnip1; Synonyms=Abin, Naf1;
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] (ISOFORMS 1 AND 2).
RX PubMed=10385526; DOI=10.1083/jcb.145.7.1471;
RA Heyninck K., De Valck D., Vanden Berghe W., Van Criekinge W., Contreras R.,
RA Fiers W., Haegeman G., Beyaert R.;
RT "The zinc finger protein A20 inhibits TNF-induced NF-B-dependent gene
RT expression by interfering with an RIP- or TRAF2-mediated transactivation
RT signal and directly binds to a novel NF-B-inhibiting protein ABIN.";
RL J. Cell Biol. 145:1471-1482(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 97-647 (ISOFORM 3).
RX PubMed=11090181; DOI=10.1128/jvi.74.24.11811-11824.2000;
RA Gupta K., Ott D., Hope T.J., Siliciano R.F., Boeke J.D.;
RT "A human nuclear shuttling protein that interacts with human
RT immunodeficiency virus type 1 matrix is packaged into virions.";
RL J. Virol. 74:11811-11824(2000).
RN [4]
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 [5]
RP FUNCTION, INTERACTION WITH TNFAIP3, AND MUTAGENESIS OF 477-GLN-GLN-478;
RP 485-ASP-PHE-486 AND 493-ARG-GLU-494.
RX PubMed=12586352; DOI=10.1016/s0014-5793(03)00041-3;
RA Heyninck K., Kreike M.M., Beyaert R.;
RT "Structure-function analysis of the A20-binding inhibitor of NF-kappa B
RT activation, ABIN-1.";
RL FEBS Lett. 536:135-140(2003).
RN [6]
RP INTERACTION WITH IKBKG, UBIQUITIN-BINDING, AND MUTAGENESIS OF
RP 485-ASP-PHE-486 AND 489-GLU-ARG-490.
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 [7]
RP FUNCTION, UBIQUITIN-BINDING, AND MUTAGENESIS OF ASP-485.
RX PubMed=21606507; DOI=10.1084/jem.20102177;
RA Nanda S.K., Venigalla R.K., Ordureau A., Patterson-Kane J.C., Powell D.W.,
RA Toth R., Arthur J.S., Cohen P.;
RT "Polyubiquitin binding to ABIN1 is required to prevent autoimmunity.";
RL J. Exp. Med. 208:1215-1228(2011).
RN [8]
RP FUNCTION, INTERACTION WITH MYD88, AND DISRUPTION PHENOTYPE.
RX PubMed=22011580; DOI=10.1073/pnas.1106232108;
RA Zhou J., Wu R., High A.A., Slaughter C.A., Finkelstein D., Rehg J.E.,
RA Redecke V., Hacker H.;
RT "A20-binding inhibitor of NF-kappaB (ABIN1) controls Toll-like receptor-
RT mediated CCAAT/enhancer-binding protein beta activation and protects from
RT inflammatory disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:E998-1006(2011).
RN [9]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-584, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-
CC dependent gene expression by regulating A20/TNFAIP3-mediated
CC deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to
CC ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2
CC signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-
CC dependent transcription. Increases cell surface CD4(T4) antigen
CC expression. Involved in the anti-inflammatory response of macrophages
CC and positively regulates TLR-induced activation of CEBPB. Involved in
CC the prevention of autoimmunity; this function implicates binding to
CC polyubiquitin. Involved in leukocyte integrin activation during
CC inflammation; this function is mediated by association with SELPLG and
CC dependent on phosphorylation by SRC-family kinases.
CC {ECO:0000269|PubMed:12586352, ECO:0000269|PubMed:21606507,
CC ECO:0000269|PubMed:22011580}.
CC -!- SUBUNIT: Interacts with TNFAIP3 and IKBKG (polyubiquitinated);
CC facilitates TNFAIP3-mediated de-ubiquitination of NEMO/IKBKG. Interacts
CC with polyubiquitin. Interacts with MAPK1, SELPLG and PIK3CD. Interacts
CC with IRAK1 (polyubiquitinated). Interacts with MYD88; the interaction
CC is indicative for participation in an activated TLR-signaling complex.
CC {ECO:0000269|PubMed:11389905, ECO:0000269|PubMed:12586352,
CC ECO:0000269|PubMed:18212736, ECO:0000269|PubMed:22011580}.
CC -!- INTERACTION:
CC Q9WUU8; P22366: Myd88; NbExp=3; IntAct=EBI-6126152, EBI-525108;
CC Q9WUU8; Q60769: Tnfaip3; NbExp=4; IntAct=EBI-6126152, EBI-646595;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Shuttles between the nucleus and cytoplasm in a CRM1-dependent
CC manner. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=ABINl;
CC IsoId=Q9WUU8-1; Sequence=Displayed;
CC Name=2; Synonyms=ABINs;
CC IsoId=Q9WUU8-2; Sequence=VSP_003914;
CC Name=3;
CC IsoId=Q9WUU8-3; Sequence=VSP_003915;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Abundant in heart and skeletal muscle
CC and expressed at lower levels in thymus, liver, kidney, brain and
CC intestinal tract.
CC -!- PTM: Phosphorylation at Tyr-565 by SRC-family kinases recruits
CC phosphoinositide-3-kinase (PI3K) PIK3CD:p85 heterodimer which results
CC in integrin activation and leukocyte adhesion to activated endothelium
CC during inflammation. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal. Mice develop an inflammatory
CC disease with characteristics of human systemic lupus erythematosus
CC (SLE), including the appearance of immature granulocytes in the
CC peripheral blood and development of autoreactive antibodies and
CC glomerulonephrititis. {ECO:0000269|PubMed:22011580}.
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DR EMBL; AJ242777; CAB44239.1; -; mRNA.
DR EMBL; AJ242778; CAB44240.1; -; mRNA.
DR EMBL; BC008186; AAH08186.1; -; mRNA.
DR EMBL; BC008665; AAH08665.1; -; mRNA.
DR EMBL; AX011241; CAC07546.1; -; Unassigned_DNA.
DR EMBL; AY012159; AAG42155.2; -; mRNA.
DR CCDS; CCDS24704.1; -. [Q9WUU8-1]
DR CCDS; CCDS56769.1; -. [Q9WUU8-2]
DR CCDS; CCDS70188.1; -. [Q9WUU8-3]
DR RefSeq; NP_001186205.1; NM_001199276.2. [Q9WUU8-2]
DR RefSeq; NP_001258384.1; NM_001271455.1. [Q9WUU8-2]
DR RefSeq; XP_006533910.1; XM_006533847.3. [Q9WUU8-2]
DR RefSeq; XP_011247465.1; XM_011249163.2. [Q9WUU8-2]
DR PDB; 6N5M; X-ray; 3.01 A; B/D=463-532.
DR PDB; 6N6R; X-ray; 1.95 A; B/D=463-532.
DR PDB; 6N6S; X-ray; 3.00 A; A/B/C/D=463-532.
DR PDBsum; 6N5M; -.
DR PDBsum; 6N6R; -.
DR PDBsum; 6N6S; -.
DR AlphaFoldDB; Q9WUU8; -.
DR SMR; Q9WUU8; -.
DR BioGRID; 208329; 6.
DR DIP; DIP-59199N; -.
DR IntAct; Q9WUU8; 6.
DR STRING; 10090.ENSMUSP00000018482; -.
DR iPTMnet; Q9WUU8; -.
DR PhosphoSitePlus; Q9WUU8; -.
DR EPD; Q9WUU8; -.
DR MaxQB; Q9WUU8; -.
DR PaxDb; Q9WUU8; -.
DR PRIDE; Q9WUU8; -.
DR ProteomicsDB; 258793; -. [Q9WUU8-1]
DR ProteomicsDB; 258794; -. [Q9WUU8-2]
DR ProteomicsDB; 258795; -. [Q9WUU8-3]
DR Antibodypedia; 28121; 307 antibodies from 28 providers.
DR DNASU; 57783; -.
DR Ensembl; ENSMUST00000108885; ENSMUSP00000104513; ENSMUSG00000020400. [Q9WUU8-2]
DR Ensembl; ENSMUST00000108886; ENSMUSP00000104514; ENSMUSG00000020400. [Q9WUU8-2]
DR GeneID; 57783; -.
DR KEGG; mmu:57783; -.
DR UCSC; uc007iyn.2; mouse. [Q9WUU8-1]
DR CTD; 10318; -.
DR MGI; MGI:1926194; Tnip1.
DR VEuPathDB; HostDB:ENSMUSG00000020400; -.
DR eggNOG; ENOG502QPYT; Eukaryota.
DR GeneTree; ENSGT00510000046908; -.
DR InParanoid; Q9WUU8; -.
DR PhylomeDB; Q9WUU8; -.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR BioGRID-ORCS; 57783; 12 hits in 73 CRISPR screens.
DR ChiTaRS; Tnip1; mouse.
DR PRO; PR:Q9WUU8; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9WUU8; protein.
DR Bgee; ENSMUSG00000020400; Expressed in small intestine Peyer's patch and 258 other tissues.
DR ExpressionAtlas; Q9WUU8; baseline and differential.
DR Genevisible; Q9WUU8; 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:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISS:UniProtKB.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0009101; P:glycoprotein biosynthetic process; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:1903003; P:positive regulation of protein deubiquitination; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR033372; TNIP1.
DR PANTHER; PTHR31882:SF3; PTHR31882:SF3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW Inflammatory response; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..647
FT /note="TNFAIP3-interacting protein 1"
FT /id="PRO_0000096692"
FT REGION 61..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..425
FT /note="Interaction with Nef"
FT REGION 444..601
FT /note="Required for inhibitory activity of TNF-induced NF-
FT kappa-B activation"
FT REGION 465..523
FT /note="Ubiquitin-binding domain (UBD)"
FT REGION 613..647
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 39..72
FT /evidence="ECO:0000255"
FT COILED 209..270
FT /evidence="ECO:0000255"
FT COILED 311..551
FT /evidence="ECO:0000255"
FT MOTIF 537..543
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 96..154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15025"
FT MOD_RES 297
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15025"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15025"
FT MOD_RES 455
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15025"
FT MOD_RES 565
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q15025"
FT MOD_RES 584
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 612
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q15025"
FT MOD_RES 612
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q15025"
FT MOD_RES 638
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15025"
FT VAR_SEQ 1..53
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10385526"
FT /id="VSP_003914"
FT VAR_SEQ 638..647
FT /note="SADNDCDGPQ -> PADLRLPKV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11090181,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_003915"
FT MUTAGEN 477..478
FT /note="QQ->EE: Loss of inhibitory activity on TNF-induced
FT NF-kappa-B activation; no effect on interaction with
FT TNFAIP3."
FT /evidence="ECO:0000269|PubMed:12586352"
FT MUTAGEN 485..486
FT /note="DF->NA: Abolishes ubiquitin binding; loss of
FT inhibitory activity on TNF-induced NF-kappa-B activation;
FT no effect on interaction with TNFAIP3."
FT /evidence="ECO:0000269|PubMed:12586352,
FT ECO:0000269|PubMed:18212736"
FT MUTAGEN 485
FT /note="D->N: Abolishes interaction with polyubiquitinated
FT IRAK1."
FT /evidence="ECO:0000269|PubMed:21606507"
FT MUTAGEN 489..490
FT /note="ER->AA: Abolishes ubiquitin binding; loss of
FT inhibitory activity on NF-kappa-B activation."
FT /evidence="ECO:0000269|PubMed:18212736"
FT MUTAGEN 493..494
FT /note="RE->AQ: Loss of inhibitory activity on TNF-induced
FT NF-kappa-B activation; no effect on interaction with
FT TNFAIP3."
FT /evidence="ECO:0000269|PubMed:12586352"
FT CONFLICT 97..98
FT /note="VQ -> TR (in Ref. 3; AAG42155)"
FT /evidence="ECO:0000305"
FT CONFLICT 308
FT /note="A -> V (in Ref. 2; AAH08186)"
FT /evidence="ECO:0000305"
FT CONFLICT 533
FT /note="A -> V (in Ref. 2; AAH08186)"
FT /evidence="ECO:0000305"
FT HELIX 465..529
FT /evidence="ECO:0007829|PDB:6N6R"
SQ SEQUENCE 647 AA; 73050 MW; 4280879A8C24A16E CRC64;
MEGRGPYRIY DPGGSTPLGE VSAAFERLVE ENTRLKGKMQ GIKMLGELLE ESQMEASRLR
QKAEELVKDS ELSPPTSAPS LVSFDDLAEL TGQDTKVQVH PATSTAATTT ATATTGNSME
KPEPASKSPS NGASSDFEVV PTEEQNSPET GSHPTNMMDL GPPPPEDSNL KLHLQRLETT
LSVCAEEPDH SQLFTHLGRM ALEFNRLASK VHKNEQRTSI LQTLCEQLRQ ENEALKAKLD
KGLEQRDLAA ERLREENTEL KKLLMNSSCK EGLCGQPSSP KPEGAGKKGV AGQQQASVMA
SKVPEAGAFG AAEKKVKLLE QQRMELLEVN KQWDQHFRSM KQQYEQKITE LRQKLVDLQK
QVTELEAERE QKQRDFDRKL LLAKSKIEME ETDKEQLTAE AKELRQKVRY LQDQLSPLTR
QREYQEKEIQ RLNKALEEAL SIQASPSSPP AAFGSPEGVG GHLRKQELVT QNELLKQQVK
IFEEDFQRER SDRERMNEEK EELKKQVEKL QAQVTLTNAQ LKTLKEEEKA KEALKQQKRK
AKASGERYHM EPHPEHVCGA YPYAYPPMPA MVPHHAYKDW SQIRYPPPPV PMEHPPPHPN
SRLFHLPEYT WRPPCAGIRN QSSQVMDPPP DRPAEPESAD NDCDGPQ
