SPATA2

Last update 08 May 2025

Basic Info

Synonyms

KIAA0757, PD1, PPP1R145

+ [4]

Introduction

Bridging factor that mediates the recruitment of CYLD to the LUBAC complex, thereby regulating TNF-alpha-induced necroptosis (PubMed:27307491, PubMed:27458237, PubMed:27545878, PubMed:27591049). Acts as a direct binding intermediate that bridges RNF31/HOIP, the catalytic subunit of the LUBAC complex, and the deubiquitinase (CYLD), thereby recruiting CYLD to the TNF-R1 signaling complex (TNF-RSC) (PubMed:27458237, PubMed:27545878, PubMed:27591049). Required to activate the 'Met-1'- (linear) and 'Lys-63'-linked deubiquitinase activities of CYLD (PubMed:27458237, PubMed:27591049). Controls the kinase activity of RIPK1 and TNF-alpha-induced necroptosis by promoting 'Met-1'-linked deubiquitination of RIPK1 by CYLD (By similarity).

100 Clinical Results associated with SPATA2

100 Translational Medicine associated with SPATA2

0 Patents (Medical) associated with SPATA2

Literatures (Medical) associated with SPATA2

01 May 2025·International Journal of Biological Macromolecules

Whole genome sequencing revealed genetic structure, domestication, and selection of Chinese indigenous ducks

Article

Author: Xiong, Rui ; Li, Jiawei ; Zhu, Yihao ; Tan, Hongli ; Huang, Yuxuan ; Gong, Yujie ; Fang, Xinyan ; Min, Huang ; Jing, Zhou ; Ouyang, Jing ; Hao, Chen ; Zheng, Sumei ; Wang, Yanan ; Wu, Liping ; Miao, Junjie ; Wu, Yan ; Yan, Xueming ; Tang, Hongbo ; Wang, Lei ; Xuan, Rui ; Luo, Keyi

The genetic architecture and domestication history of Chinese indigenous ducks, particularly those with distinct traits like the Longsheng duck (LSD), are not well characterized. This study used whole-genome resequencing data from 540 ducks across 30 populations to explore the genetic diversity and structure of these ducks. Our findings suggest extensive interspecific hybridization between mallard and spot-billed duck. Comparing with other Chinese ducks, LSD is a distinct breed with moderate genetic diversity. Selective signal analysis identified several key genes impacting neural development, fat metabolism, immunity, and circadian rhythms like SLC25A20 and PER2. These genes showed strong selective pressures that parallelled other domestication processes. Additionally, EDNRB2 was identified as a potential gene influencing the unique coloration of LSD's plumage, bill, and webbed feet, associated with distinct mutations in non-coding regions. Comparative analysis with other indigenous breeds further pinpointed genes associated with LSD-specific traits, including plumage color, reproductive capabilities, and fat deposition, such as MITF, SPATA2, EIF2S2, PLIN3, ATP1B1, and CCDC80. Our findings clarify the population genetics of Chinese indigenous ducks. They also highlight key genes and mutations that shape the unique characteristics of LSD. These insights pave the way for further research into the genetic resources and domestication patterns of Chinese ducks.

01 Apr 2025·Actas Dermo-Sifiliográficas

Genetic polymorphisms in psoriasis: investigating genetic variations for precise profiling of response to brodalumab in real-life clinical practice

Article

Author: Armesto, S ; Sahuquillo-Torralba, A ; Ruiz-Villaverde, R ; Ovejero-Benito, M C ; Roustan, G ; Novalbos, Jesús ; Daudén, E ; Navares, M ; Llamas-Velasco, M ; Pujol-Montcusí, J ; Palomar-Moreno, C ; de la Cueva, P ; Abad-Santos, F ; Butrón-Bris, B ; Martínez-López, A ; Vilarrasa-Rull, E ; Ferrán-Farrés, M ; de la Fuente, H ; Romero-Maté, A

BACKGROUNDNumerous studies have investigated the association that exists between genetic variants and the efficacy profile of biologic therapies for the management of psoriasis. However, as far as we know, data on this association for brodalumab are lacking in the currently available scientific literature.OBJECTIVESTo analyze the association of 180 polymorphisms with an optimal response to brodalumab in real-world clinical practice.METHODSA total of 119 patients with plaque psoriasis on a 24-regimen of brodalumab recruited from 11 Spanish hospitals were genotyped for 180 polymorphisms. Optimal response was evaluated as absolute (PASI) ≤ 1 at 6 and 12 months. Polymorphisms with false discovery rates < 0.25 were included in a multiple regression model.RESULTSA total of 68% and 62% of patients achieved PASI ≤ 1 at 6 and 12 months, respectively. Patient weight, history of biological therapy, disease-modifying anti-rheumatic drugs, and psoriatic arthritis were identified as risk factors for failing to achieve PASI ≤1. At 12 months, polymorphisms rs495337 (SPATA2), rs6311 (HTR2A), and rs4085613 (LCE3D) were associated with achieving a PASI ≤1 regardless of previous use of biologics and DMARDs, psoriatic arthritis, or weight. The genotypes CT-TT for rs6311 (HTR2A) and GT for rs4085613 (LCE3D) were identified as risk factors for lack of optimal response at 12 months, while genotypes AG-AA for rs495337 (SPATA2) increase the probability of response. No polymorphism was associated to brodalumab response at 6 months.CONCLUSIONSThis study identified genetic variations associated with the ability to achieve an optimal response to brodalumab, providing potential insights into its efficacy profile for treating plaque psoriasis.

01 Apr 2025·Journal of Cellular and Molecular Medicine

Unravelling Cancer Immunity: Coagulation.Sig and BIRC2 as Predictive Immunotherapeutic Architects

Article

Author: Zhang, Xiang ; Yao, Ziang ; Bai, Yucheng ; Zhang, Renquan ; Fan, Jun ; Xue, Lei ; He, Jiakai

ABSTRACTImmune checkpoint inhibitors (ICIs) represent a groundbreaking advancement in cancer therapy, substantially improving patient survival rates. Our comprehensive research reveals a significant positive correlation between coagulation scores and immune‐related gene expression across 30 diverse cancer types. Notably, tumours exhibiting high coagulation scores demonstrated enhanced infiltration of cytotoxic immune cells, including CD8+ T cells, natural killer (NK) cells, and macrophages. Leveraging the TCGA pan‐cancer database, we developed the Coagulation.Sig model, a sophisticated predictive framework utilising a coagulation‐related genes (CRGs) to forecast immunotherapy outcomes. Through rigorous analysis of ten ICI‐treated cohorts, we identified and validated seven critical CRGs: BIRC2, HMGB1, STAT2, IFNAR1, BID, SPATA2, IL33 and IFNG, which form the foundation of our predictive model. Functional analyses revealed that low‐risk tumours characterised by higher immune cell populations, particularly CD8+ T cells, demonstrated superior ICI responses. These tumours also exhibited increased mutation rates, elevated neoantigen loads, and greater TCR/BCR diversity. Conversely, high‐risk tumours displayed pronounced intratumor heterogeneity (ITH) and elevated NRF2 pathway activity, mechanisms strongly associated with immune evasion. Experimental validation highlighted BIRC2 as a promising therapeutic target. Targeted BIRC2 knockdown, when combined with anti‐PD‐1 therapy, significantly suppressed tumour growth, enhanced CD8+ T cell infiltration, and amplified IFN‐γ and TNF‐α secretion in tumour models. Our findings position the Coagulation.Sig model as a novel, comprehensive approach to personalised cancer treatment, with BIRC2 emerging as both a predictive biomarker and a potential therapeutic intervention point.

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SPATA2

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