TNIP1 explained

TNFAIP3-interacting protein 1, also known as ABIN-1, is a protein that in humans is encoded by the TNIP1 gene.^{[1] [2] [3]}

Association with autoimmune diseases

Genetic variations within the region of the TNIP1 gene have been shown to have association with several autoimmune diseases:

• Systemic Sclerosis

^[4]

• Psoriasis

^[5]

• Psoriatic arthritis

^[6]

• Systemic Lupus Erythematosus^{[7] [8]}
• Type-1 autoimmune hepatitis^[9]
• Lupus nephritis^[10]

TNIP1 dysfunction or deficiency contributes to hyperinflammarion and may predispose healthy cells to the inflammatory response to otherwise innocuous TLR ligand exposure.^[11]

Association with neurodegenerative diseases

A recent genome-wide association study (GWAS) has found that genetic variations in TNIP1 are associated with late-onset sporadic Alzheimer’s disease (LOAD).^[12]

Interactions

TNIP1 contains multiple amino acid sites that are phosphorylated and ubiquitinated,^[13] and has been shown to interact with TNFAIP3,^[14] MAP3K1,^[15] and MAPK1.^[16]

Regulation

TNIP1 was shown to be part of a transcription module controlled by BCL3. BCL3 gen was found to be strongly associated with Aβ42 after conditioning for APOE and was found as upregulated in the brain of patients with LOAD.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T . Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones . DNA Research . 9 . 3 . 99–106 . June 2002 . 12168954 . 10.1093/dnares/9.3.99 . 10.1.1.500.923 .
• Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H . 6 . Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1 . DNA Research . 2 . 1 . 37–43 . 1995 . 7788527 . 10.1093/dnares/2.1.37 . free .
• Loftus SK, Dixon J, Koprivnikar K, Dixon MJ, Wasmuth JJ . Transcriptional map of the Treacher Collins candidate gene region . Genome Research . 6 . 1 . 26–34 . January 1996 . 8681136 . 10.1101/gr.6.1.26 . free .
• Jäkel S, Görlich D . Importin beta, transportin, RanBP5 and RanBP7 mediate nuclear import of ribosomal proteins in mammalian cells . The EMBO Journal . 17 . 15 . 4491–4502 . August 1998 . 9687515 . 1170780 . 10.1093/emboj/17.15.4491 .
• Heyninck K, De Valck D, Vanden Berghe W, Van Criekinge W, Contreras R, Fiers W, Haegeman G, Beyaert R . 6 . The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaB-inhibiting protein ABIN . The Journal of Cell Biology . 145 . 7 . 1471–1482 . June 1999 . 10385526 . 2133159 . 10.1083/jcb.145.7.1471 .
• Zhang S, Fukushi M, Hashimoto S, Gao C, Huang L, Fukuyo Y, Nakajima T, Amagasa T, Enomoto S, Koike K, Miura O, Yamamoto N, Tsuchida N . 6 . A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling . Biochemical and Biophysical Research Communications . 297 . 1 . 17–23 . September 2002 . 12220502 . 10.1016/S0006-291X(02)02086-7 .
• Leonard D, Ajuh P, Lamond AI, Legerski RJ . hLodestar/HuF2 interacts with CDC5L and is involved in pre-mRNA splicing . Biochemical and Biophysical Research Communications . 308 . 4 . 793–801 . September 2003 . 12927788 . 10.1016/S0006-291X(03)01486-4 . 10.1.1.539.8359 .
• Gallagher J, Howlin J, McCarthy C, Murphy EP, Bresnihan B, FitzGerald O, Godson C, Brady HR, Martin F . 6 . Identification of Naf1/ABIN-1 among TNF-alpha-induced expressed genes in human synoviocytes using oligonucleotide microarrays . FEBS Letters . 551 . 1–3 . 8–12 . September 2003 . 12965196 . 10.1016/S0014-5793(03)00823-8 . 2796577 .
• Favre M, Butticaz C, Stevenson B, Jongeneel CV, Telenti A . High frequency of alternative splicing of human genes participating in the HIV-1 life cycle: a model using TSG101, betaTrCP, PPIA, INI1, NAF1, and PML . Journal of Acquired Immune Deficiency Syndromes . 34 . 2 . 127–133 . October 2003 . 14526201 . 10.1097/00126334-200310010-00002 . free .
• Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G . 6 . A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway . Nature Cell Biology . 6 . 2 . 97–105 . February 2004 . 14743216 . 10.1038/ncb1086 . 11683986 .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . 6 . Functional proteomics mapping of a human signaling pathway . Genome Research . 14 . 7 . 1324–1332 . July 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . 6 . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–1718 . September 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Hoareau-Aveilla C, Bonoli M, Caizergues-Ferrer M, Henry Y . hNaf1 is required for accumulation of human box H/ACA snoRNPs, scaRNPs, and telomerase . RNA . 12 . 5 . 832–840 . May 2006 . 16601202 . 1440901 . 10.1261/rna.2344106 .

Notes and References

1. Fukushi M, Dixon J, Kimura T, Tsurutani N, Dixon MJ, Yamamoto N . Identification and cloning of a novel cellular protein Naf1, Nef-associated factor 1, that increases cell surface CD4 expression . FEBS Letters . 442 . 1 . 83–88 . January 1999 . 9923610 . 10.1016/S0014-5793(98)01631-7 . 86298611 . free .
2. Gupta K, Ott D, Hope TJ, Siliciano RF, Boeke JD . A human nuclear shuttling protein that interacts with human immunodeficiency virus type 1 matrix is packaged into virions . Journal of Virology . 74 . 24 . 11811–11824 . December 2000 . 11090181 . 112464 . 10.1128/JVI.74.24.11811-11824.2000 .
3. Web site: Entrez Gene: TNIP1 TNFAIP3 interacting protein 1.
4. Allanore Y, Saad M, Dieudé P, Avouac J, Distler JH, Amouyel P, Matucci-Cerinic M, Riemekasten G, Airo P, Melchers I, Hachulla E, Cusi D, Wichmann HE, Wipff J, Lambert JC, Hunzelmann N, Tiev K, Caramaschi P, Diot E, Kowal-Bielecka O, Valentini G, Mouthon L, Czirják L, Damjanov N, Salvi E, Conti C, Müller M, Müller-Ladner U, Riccieri V, Ruiz B, Cracowski JL, Letenneur L, Dupuy AM, Meyer O, Kahan A, Munnich A, Boileau C, Martinez M . 6 . Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis . PLOS Genetics . 7 . 7 . e1002091 . July 2011 . 21750679 . 3131285 . 10.1371/journal.pgen.1002091 . free .
5. Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, Gudjonsson JE, Li Y, Tejasvi T, Feng BJ, Ruether A, Schreiber S, Weichenthal M, Gladman D, Rahman P, Schrodi SJ, Prahalad S, Guthery SL, Fischer J, Liao W, Kwok PY, Menter A, Lathrop GM, Wise CA, Begovich AB, Voorhees JJ, Elder JT, Krueger GG, Bowcock AM, Abecasis GR . 6 . Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways . Nature Genetics . 41 . 2 . 199–204 . February 2009 . 19169254 . 2745122 . 10.1038/ng.311 .
6. Bowes J, Orozco G, Flynn E, Ho P, Brier R, Marzo-Ortega H, Coates L, McManus R, Ryan AW, Kane D, Korendowych E, McHugh N, FitzGerald O, Packham J, Morgan AW, Bruce IN, Barton A . 6 . Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic arthritis . Annals of the Rheumatic Diseases . 70 . 9 . 1641–1644 . September 2011 . 21623003 . 3147229 . 10.1136/ard.2011.150102 .
7. Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, Ortmann W, Kosoy R, Ferreira RC, Nordmark G, Gunnarsson I, Svenungsson E, Padyukov L, Sturfelt G, Jönsen A, Bengtsson AA, Rantapää-Dahlqvist S, Baechler EC, Brown EE, Alarcón GS, Edberg JC, Ramsey-Goldman R, McGwin G, Reveille JD, Vilá LM, Kimberly RP, Manzi S, Petri MA, Lee A, Gregersen PK, Seldin MF, Rönnblom L, Criswell LA, Syvänen AC, Behrens TW, Graham RR . 6 . A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus . Nature Genetics . 41 . 11 . 1228–1233 . November 2009 . 19838195 . 2925843 . 10.1038/ng.468 .
8. Han JW, Zheng HF, Cui Y, Sun LD, Ye DQ, Hu Z, Xu JH, Cai ZM, Huang W, Zhao GP, Xie HF, Fang H, Lu QJ, Xu JH, Li XP, Pan YF, Deng DQ, Zeng FQ, Ye ZZ, Zhang XY, Wang QW, Hao F, Ma L, Zuo XB, Zhou FS, Du WH, Cheng YL, Yang JQ, Shen SK, Li J, Sheng YJ, Zuo XX, Zhu WF, Gao F, Zhang PL, Guo Q, Li B, Gao M, Xiao FL, Quan C, Zhang C, Zhang Z, Zhu KJ, Li Y, Hu DY, Lu WS, Huang JL, Liu SX, Li H, Ren YQ, Wang ZX, Yang CJ, Wang PG, Zhou WM, Lv YM, Zhang AP, Zhang SQ, Lin D, Li Y, Low HQ, Shen M, Zhai ZF, Wang Y, Zhang FY, Yang S, Liu JJ, Zhang XJ . 6 . Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus . Nature Genetics . 41 . 11 . 1234–1237 . November 2009 . 19838193 . 10.1038/ng.472 . 205356205 .
9. Oka S, Higuchi T, Furukawa H, Nakamura M, Komori A, Abiru S, Nagaoka S, Hashimoto S, Naganuma A, Naeshiro N, Yoshizawa K, Shimada M, Nishimura H, Tomizawa M, Kikuchi M, Makita F, Yamashita H, Ario K, Yatsuhashi H, Tohma S, Kawasaki A, Tsuchiya N, Migita K . 6 . Association of a single nucleotide polymorphism in TNIP1 with type-1 autoimmune hepatitis in the Japanese population . Journal of Human Genetics . 63 . 6 . 739–744 . June 2018 . 29559739 . 10.1038/s10038-018-0440-0 . 4477603 .
10. Brady MP, Korte EA, Caster DJ, Powell DW . TNIP1/ABIN1 and lupus nephritis: review . Lupus Science & Medicine . 7 . 1 . e000437 . October 2020 . 33122334 . 7597513 . 10.1136/lupus-2020-000437 .
11. Shamilov R, Aneskievich BJ . TNIP1 in Autoimmune Diseases: Regulation of Toll-like Receptor Signaling . Journal of Immunology Research . 2018 . 3491269 . 2018-10-03 . 30402506 . 6192141 . 10.1155/2018/3491269 . free .
12. Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, Rongve A, Børte S, Winsvold BS, Drange OK, Martinsen AE, Skogholt AH, Willer C, Bråthen G, Bosnes I, Nielsen JB, Fritsche LG, Thomas LF, Pedersen LM, Gabrielsen ME, Johnsen MB, Meisingset TW, Zhou W, Proitsi P, Hodges A, Dobson R, Velayudhan L, Heilbron K, Auton A, Sealock JM, Davis LK, Pedersen NL, Reynolds CA, Karlsson IK, Magnusson S, Stefansson H, Thordardottir S, Jonsson PV, Snaedal J, Zettergren A, Skoog I, Kern S, Waern M, Zetterberg H, Blennow K, Stordal E, Hveem K, Zwart JA, Athanasiu L, Selnes P, Saltvedt I, Sando SB, Ulstein I, Djurovic S, Fladby T, Aarsland D, Selbæk G, Ripke S, Stefansson K, Andreassen OA, Posthuma D . 6 . A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease . Nature Genetics . 53 . 9 . 1276–1282 . September 2021 . 34493870 . 10.1038/s41588-021-00921-z. 10243600 . 1061-4036 . 237442349 . 1871.1/61f01aa9-6dc7-4213-be2a-d3fe622db488 . free .
13. Web site: TNIP1 (human). 2020-10-31. www.phosphosite.org.
14. Heyninck K, De Valck D, Vanden Berghe W, Van Criekinge W, Contreras R, Fiers W, Haegeman G, Beyaert R . 6 . The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaB-inhibiting protein ABIN . The Journal of Cell Biology . 145 . 7 . 1471–1482 . June 1999 . 10385526 . 2133159 . 10.1083/jcb.145.7.1471 .
15. Charlaftis N, Suddason T, Wu X, Anwar S, Karin M, Gallagher E . The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines . The EMBO Journal . 33 . 21 . 2581–2596 . November 2014 . 25260751 . 4282369 . 10.15252/embj.201488351 .
16. Zhang S, Fukushi M, Hashimoto S, Gao C, Huang L, Fukuyo Y, Nakajima T, Amagasa T, Enomoto S, Koike K, Miura O, Yamamoto N, Tsuchida N . 6 . A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling . Biochemical and Biophysical Research Communications . 297 . 1 . 17–23 . September 2002 . 12220502 . 10.1016/S0006-291X(02)02086-7 .