# ANLN

## Overview
ANLN is a gene that encodes the protein anillin, an actin-binding protein that plays a critical role in cytokinesis, the process of cell division. Anillin functions as a scaffold protein, coordinating the assembly and stabilization of the contractile ring by interacting with actin, myosin, and other cytoskeletal components. It is characterized by several functional domains, including an N-terminal actin-binding domain, a central pleckstrin homology (PH) domain, and a C-terminal region that interacts with septins and myosin, facilitating its role in cellular processes (Oegema2000Functional; Piekny2008Anillin). The protein is subject to post-translational modifications, such as phosphorylation, which regulate its activity during cell division (Field1995Anillin). ANLN is implicated in various cellular functions beyond cytokinesis, including DNA replication and repair, and its dysregulation is associated with several cancers, making it a potential biomarker and therapeutic target (Tong2024ANLN; Liu2022Pan-cancer).

## Structure
Anillin (ANLN) is a human protein with a complex molecular structure that plays a crucial role in cytokinesis. The protein is composed of 1,125 amino acids and has a predicted molecular mass of 124 kDa, although it appears larger on SDS-PAGE, likely due to post-translational modifications (Oegema2000Functional). The primary structure of anillin includes several key domains: an N-terminal actin-binding domain, a central pleckstrin homology (PH) domain, and a C-terminal region that interacts with septins and myosin (Oegema2000Functional; Piekny2008Anillin).

The PH domain is highly conserved and essential for anillin's localization and function, particularly in membrane targeting and interaction with septins (Paolo2009How; Oegema2000Functional). The actin-binding domain is located in the N-terminal region and is crucial for the protein's role in the cleavage furrow during cell division (Oegema2000Functional). Anillin also contains several nuclear localization sequences and SH3 binding motifs, which may facilitate its interactions with other proteins (Oegema2000Functional).

Post-translational modifications, such as phosphorylation, regulate anillin's activity during cell division (Field1995Anillin). Multiple splice variants of ANLN exist, potentially affecting its interaction with other proteins and cellular localization (Piekny2008Anillin). These structural features enable anillin to function as a scaffold protein, linking actin, myosin, and RhoA during cytokinesis (Piekny2008Anillin).

## Function


## Clinical Significance
Mutations and alterations in the ANLN gene have significant clinical implications, particularly in cancer. ANLN is overexpressed in various cancers, including breast, lung, pancreatic, liver, bladder, and colorectal cancers, and is associated with poor prognosis due to its role in promoting tumor progression (Liu2022Pan-cancer; Shi2022Comprehensive). High ANLN expression is linked to advanced pathological stages and poor overall survival in several cancer types, such as adrenocortical carcinoma, bladder urothelial carcinoma, and lung adenocarcinoma (Liu2022Pan-cancer). 

In pancreatic cancer, high ANLN expression is an independent prognostic factor associated with poor survival and higher tumor grade (Nie2020Anillin). ANLN's role in tumor immune evasion is highlighted by its involvement in T-cell exclusion and interactions with tumor-infiltrating immune cells, particularly in colon adenocarcinoma and liver hepatocellular carcinoma (Liu2022Pan-cancer). 

Additionally, ANLN mutations, such as the missense variant c.G1105A, have been linked to branchio-otic syndrome, a genetic disorder affecting ear and neck development (Deng2018Identification). These findings underscore ANLN's potential as a biomarker for cancer prognosis and a target for therapeutic interventions.

## Interactions
Anillin (ANLN) is a multifunctional protein that interacts with various proteins to regulate cellular processes. It contains several domains that facilitate these interactions. The N-terminal region of anillin includes an actin-binding domain, allowing it to bind multiple actin molecules and interact with non-muscle myosin II (NM II), DIAPH3, and CD2AP, which are crucial for actin polymerization and cytoskeletal regulation (Naydenov2020Anillin). The C-terminal region features an anillin homology domain (AHD) and a pleckstrin homology (PH) domain, which interact with RhoA and septin filaments, respectively. Anillin's interaction with RhoA is essential for actomyosin filament assembly and contractility (Naydenov2020Anillin).

Anillin also interacts with proliferating cell nuclear antigen (PCNA) in the context of DNA replication and repair. It directly binds to the PIP box domain of PCNA, promoting DNA replication and S phase progression in a PCNA-dependent manner. This interaction is crucial for translesion synthesis (TLS) under UV-induced stress, where anillin facilitates PCNA monoubiquitination and recruits the E3 ligase RAD18 (Tong2024ANLN). Additionally, anillin interacts with proteins involved in DNA damage repair, including those in nucleotide excision repair and mismatch repair pathways (Tong2024ANLN).


## References


[1. (Piekny2008Anillin) Alisa J. Piekny and Michael Glotzer. Anillin is a scaffold protein that links rhoa, actin, and myosin during cytokinesis. Current Biology, 18(1):30–36, January 2008. URL: http://dx.doi.org/10.1016/j.cub.2007.11.068, doi:10.1016/j.cub.2007.11.068. This article has 477 citations and is from a highest quality peer-reviewed journal.](https://doi.org/10.1016/j.cub.2007.11.068)

[2. (Nie2020Anillin) Yuanhua Nie, Zhiqiang Zhao, Minxue Chen, Fulin Ma, Yong Fan, Yingxin Kang, Boxiong Kang, and Chen Wang. Anillin is a prognostic factor and is correlated with genovariation in pancreatic cancer based on databases analysis. Oncology Letters, December 2020. URL: http://dx.doi.org/10.3892/ol.2020.12368, doi:10.3892/ol.2020.12368. This article has 4 citations and is from a peer-reviewed journal.](https://doi.org/10.3892/ol.2020.12368)

[3. (Field1995Anillin) C M Field and B M Alberts. Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex. The Journal of cell biology, 131(1):165–178, October 1995. URL: http://dx.doi.org/10.1083/jcb.131.1.165, doi:10.1083/jcb.131.1.165. This article has 340 citations.](https://doi.org/10.1083/jcb.131.1.165)

[4. (Oegema2000Functional) Karen Oegema, Matthew S. Savoian, Timothy J. Mitchison, and Christine M. Field. Functional analysis of a human homologue of the drosophila actin binding protein anillin suggests a role in cytokinesis. The Journal of Cell Biology, 150(3):539–552, August 2000. URL: http://dx.doi.org/10.1083/jcb.150.3.539, doi:10.1083/jcb.150.3.539. This article has 251 citations.](https://doi.org/10.1083/jcb.150.3.539)

[5. (Paolo2009How) Pier Paolo D’Avino. How to scaffold the contractile ring for a safe cytokinesis – lessons from anillin-related proteins. Journal of Cell Science, 122(8):1071–1079, April 2009. URL: http://dx.doi.org/10.1242/jcs.034785, doi:10.1242/jcs.034785. This article has 98 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1242/jcs.034785)

[6. (Naydenov2020Anillin) Nayden G. Naydenov, Jennifer E. Koblinski, and Andrei I. Ivanov. Anillin is an emerging regulator of tumorigenesis, acting as a cortical cytoskeletal scaffold and a nuclear modulator of cancer cell differentiation. Cellular and Molecular Life Sciences, 78(2):621–633, September 2020. URL: http://dx.doi.org/10.1007/s00018-020-03605-9, doi:10.1007/s00018-020-03605-9. This article has 27 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1007/s00018-020-03605-9)

7. (Tong2024ANLN) ANLN directly interacts with PCNA to regulate UV induced translesion synthesis. This article has 0 citations.

[8. (Deng2018Identification) Lisha Deng, Yuanzhen Liu, Wenjun Xia, Jiongjiong Hu, and Zhaoxin Ma. Identification of anln as a new likely pathogenic gene of branchio‐otic syndrome in a three‐generation chinese family. Molecular Genetics & Genomic Medicine, December 2018. URL: http://dx.doi.org/10.1002/mgg3.525, doi:10.1002/mgg3.525. This article has 3 citations.](https://doi.org/10.1002/mgg3.525)

[9. (Liu2022Pan-cancer) Kejun Liu, Lei Cui, Cunquan Li, Chaofeng Tang, Yiming Niu, Ji Hao, Yang Bu, and Bendong Chen. Pan-cancer analysis of the prognostic and immunological role of anln: an onco-immunological biomarker. Frontiers in Genetics, August 2022. URL: http://dx.doi.org/10.3389/fgene.2022.922472, doi:10.3389/fgene.2022.922472. This article has 9 citations and is from a peer-reviewed journal.](https://doi.org/10.3389/fgene.2022.922472)

[10. (Shi2022Comprehensive) Yanlong Shi, Xinyu Ma, Menglu Wang, Sheng Lan, Haokun Jian, Yue Wang, Qian Wei, and Fei Zhong. Comprehensive analyses reveal the carcinogenic and immunological roles of anln in human cancers. Cancer Cell International, May 2022. URL: http://dx.doi.org/10.1186/s12935-022-02610-1, doi:10.1186/s12935-022-02610-1. This article has 5 citations and is from a peer-reviewed journal.](https://doi.org/10.1186/s12935-022-02610-1)