CPLM-012463

Genbank Nucleotide ID

TNFAIP3-interacting protein 1

Protein Synonyms/Alias

A20-binding inhibitor of NF-kappa-B activation 1; ABIN-1; HIV-1 Nef-interacting protein; Nef-associated factor 1; Naf1; Nip40-1; Virion-associated nuclear shuttling protein; VAN; hVAN

Homo sapiens (Human)

Position	Peptide	Type	References
257	LLMSNGNKEGASGRP	acetylation	[1]
496	ELKKQVEKLQAQVTL	ubiquitination	[2]

[1] Regulation of cellular metabolism by protein lysine acetylation.
Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
[2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]

Functional Description

Interacts with zinc finger protein A20/TNFAIP3 and inhibits TNF-induced NF-kappa-B-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal; however, binding to A20/TNFAIP3 seems not to be required for this function (By similarity). Inhibits NF-kappa-B activation by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcricption. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosohorylation by SRC-family kinases. Interacts with HIV-1 matrix protein and is packaged into virions and overexpression can inhibit viral replication. May regulate matrix nuclear localization, both nuclear import of PIC (Preintegration complex) and export of GAG polyprotein and viral genomic RNA during virion production. In case of infection, promotes association of IKBKG with Shigella flexneri E3 ubiquitin-protein ligase ipah9.8 p which in turn promotes polyubiquitination of IKBKG leading to its proteasome-dependent degradation and thus is perturbing NF-kappa-B activation during bacterial infection.

REGION 94 412 Interacts with Nef.
REGION 351 367 Interaction with Shigella flexneri
REGION 431 588 Required for inhibitory activity of TNF-
REGION 452 510 Ubiquitin-binding domain (UBD).
MOTIF 524 530 Nuclear localization signal (Potential).
MOD_RES 403 403 Phosphoserine.
MOD_RES 438 438 Phosphothreonine.
MOD_RES 442 442 Phosphoserine.
MOD_RES 552 552 Phosphotyrosine.

Alternative splicing; Coiled coil; Complete proteome; Cytoplasm; Inflammatory response; Nucleus; Phosphoprotein; Polymorphism; Reference proteome.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IDA:HPA.
GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO:0051019; F:mitogen-activated protein kinase binding; IDA:UniProtKB.
GO:0006952; P:defense response; TAS:ProtInc.
GO:0009101; P:glycoprotein biosynthetic process; IDA:UniProtKB.
GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO:0007159; P:leukocyte cell-cell adhesion; IMP:UniProtKB.
GO:0085032; P:modulation by symbiont of host I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; ISS:UniProtKB.
GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; IDA:UniProtKB.
GO:0045071; P:negative regulation of viral genome replication; TAS:UniProtKB.
GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
GO:0006412; P:translation; TAS:ProtInc.