# FABP7

## Overview
Fatty acid binding protein 7 (FABP7) is a gene that encodes a member of the fatty acid-binding protein family, specifically known as brain fatty acid-binding protein. This protein is categorized as a cytoplasmic lipid-binding protein and is primarily involved in the transport and metabolism of long-chain fatty acids within the brain. FABP7 is predominantly expressed in astrocytes and neural stem cells, where it plays a crucial role in maintaining synaptic homeostasis, influencing neurodevelopmental processes, and supporting cognitive functions. The protein's structure is characterized by a beta-barrel motif that facilitates the binding of hydrophobic molecules, which is essential for its function in cellular signaling and energy metabolism. FABP7's interactions with other proteins, such as ATP-citrate lyase and peroxisome proliferator-activated receptor gamma, underscore its involvement in regulating gene expression and lipid metabolism. Clinically, alterations in FABP7 expression have been linked to various neurodegenerative diseases, cancers, and psychiatric disorders, highlighting its significance as a potential therapeutic target (Islam2019FABP7; Ebrahimi2015Astrocyte‐expressed; Kagawa2020FABP7).

## Structure
FABP7, also known as brain fatty acid-binding protein, is a member of the fatty acid-binding protein family. Its primary structure consists of 131 amino acid residues, with a molecular weight of approximately 14.7 kDa (Oeemig2009Backbone). The secondary structure of FABP7 is characterized by a beta-barrel composed of ten antiparallel beta-strands, forming a compact structure with a helix-turn-helix motif at the N-terminus, which acts as a 'lid' on top of the beta-barrel (Rademacher2002Solution; Oeemig2009Backbone). This beta-barrel encloses a large cavity that serves as the ligand-binding site (Rademacher2002Solution).

The tertiary structure of FABP7 is highly conserved among the FABP family, featuring a globular form that facilitates the binding and transport of hydrophobic molecules like long-chain fatty acids (Lenz2021FABP7). The quaternary structure involves interactions with fatty acid micelles and membranes, where FABP7 binds through specific residues located on helices and turns, such as the H3 helix and the βCD turn (Lenz2021FABP7).

FABP7 may undergo post-translational modifications, although specific modifications are not detailed in the provided context. The protein can exist in different isoforms due to alternative splicing, which may affect its function and interactions.

## Function
FABP7, or fatty acid binding protein 7, plays a critical role in the transport and metabolism of fatty acids within cells, particularly in the brain. It is primarily expressed in astrocytes and neural stem cells, where it facilitates the uptake and intracellular transport of long-chain fatty acids, influencing cell signaling, energy metabolism, and gene expression (Islam2019FABP7; Ebrahimi2015Astrocyte‐expressed). FABP7 is involved in maintaining synaptic homeostasis and complex behavioral processes by regulating dendritic morphology and excitatory synaptic function in cortical neurons. It supports the development of dendritic arbors and synaptogenesis, likely through the secretion of humoral factors such as growth factors that promote neurite extension and synaptic maturation (Ebrahimi2015Astrocyte‐expressed).

In astrocytes, FABP7 is crucial for maintaining cellular homeostasis under oxidative stress conditions. It promotes lipid droplet formation, which is essential for protecting astrocytes from reactive oxygen species (ROS) toxicity. This protective role is achieved by enhancing antioxidant defense mechanisms and modulating apoptotic signaling pathways, thereby safeguarding astrocyte integrity and supporting neuronal function (Islam2019FABP7). FABP7's activity is primarily localized in the cytoplasm, where it influences various neurodevelopmental processes and cognitive functions (Islam2019FABP7).

## Clinical Significance
Alterations in the expression of the FABP7 gene have been implicated in several diseases, particularly neurodegenerative and cancerous conditions. In the context of amyotrophic lateral sclerosis (ALS), FABP7 is upregulated in astrocytes of symptomatic ALS mouse models, contributing to a pro-inflammatory and neurotoxic environment that affects motor neuron survival (Killoy2020FABP7). This suggests that FABP7 could be a potential therapeutic target to mitigate astrocyte-mediated motor neuron toxicity in ALS.

In cancer, FABP7 is associated with various malignancies. In melanoma, FABP7 is involved in cell proliferation and invasion, and its down-regulation reduces the invasive ability of certain melanoma cell lines (Goto2006A). In glioblastoma multiforme, FABP7 is highly expressed in glioma stem-like cells, promoting tumor progression and treatment resistance (De2012A). FABP7 overexpression in clear cell renal cell carcinoma (ccRCC) is linked to higher tumor volume, advanced clinical stages, and poor prognosis, with its expression potentially regulated by DNA methylation (Zhou2015Overexpression).

FABP7 has also been associated with psychiatric disorders. A nominal association between a missense polymorphism in FABP7 and schizophrenia has been identified, suggesting a potential role in the pathophysiology of psychiatric conditions (Iwayama2010Association).

## Interactions
FABP7, or fatty acid binding protein 7, is involved in several interactions with other proteins and nucleic acids, playing a significant role in cellular processes. One of its key interactions is with ATP-citrate lyase (ACLY) in the nucleus of astrocytes. This interaction is crucial for regulating acetyl-CoA metabolism, which in turn affects histone acetylation and gene expression, including the regulation of caveolin-1, a component of lipid rafts (Kagawa2020FABP7). FABP7 enhances ACLY activity through its ligand-binding capacity, impacting acetyl-CoA levels without altering ACLY protein expression or localization (Kagawa2020FABP7).

FABP7 also interacts with peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor that acts as a transcription factor. This interaction is involved in the regulation of gene expression related to lipid metabolism and inflammation. The FABP7-PPARγ complex is influenced by docosahexaenoic acid (DHA), which enhances the interaction and affects the expression of glial fibrillary acidic protein (GFAP) in astrocytes (Tripathi2016Docosahexaenoic). These interactions highlight FABP7's role in modulating cellular activities through its involvement in lipid transport and gene regulation.


## References


[1. (Zhou2015Overexpression) Jiancheng Zhou, Zhuo Deng, Yule Chen, Yang Gao, Dapeng Wu, Guodong Zhu, Lei Li, Wenbin Song, Xinyang Wang, Kaijie Wu, and Dalin He. Overexpression of fabp7 promotes cell growth and predicts poor prognosis of clear cell renal cell carcinoma1contributed equally. Urologic Oncology: Seminars and Original Investigations, 33(3):113.e9-113.e17, March 2015. URL: http://dx.doi.org/10.1016/j.urolonc.2014.08.001, doi:10.1016/j.urolonc.2014.08.001. This article has 30 citations and is from a peer-reviewed journal.](https://doi.org/10.1016/j.urolonc.2014.08.001)

[2. (De2012A) Antonella De Rosa, Serena Pellegatta, Marco Rossi, Patrizia Tunici, Letizia Magnoni, Maria Carmela Speranza, Federico Malusa, Vincenzo Miragliotta, Elisa Mori, Gaetano Finocchiaro, and Annette Bakker. A radial glia gene marker, fatty acid binding protein 7 (fabp7), is involved in proliferation and invasion of glioblastoma cells. PLoS ONE, 7(12):e52113, December 2012. URL: http://dx.doi.org/10.1371/journal.pone.0052113, doi:10.1371/journal.pone.0052113. This article has 93 citations and is from a peer-reviewed journal.](https://doi.org/10.1371/journal.pone.0052113)

[3. (Ebrahimi2015Astrocyte‐expressed) Majid Ebrahimi, Yui Yamamoto, Kazem Sharifi, Hiroyuki Kida, Yoshiteru Kagawa, Yuki Yasumoto, Ariful Islam, Hirofumi Miyazaki, Chie Shimamoto, Motoko Maekawa, Dai Mitsushima, Takeo Yoshikawa, and Yuji Owada. Astrocyte‐expressed <scp>fabp</scp>7 regulates dendritic morphology and excitatory synaptic function of cortical neurons. Glia, 64(1):48–62, August 2015. URL: http://dx.doi.org/10.1002/glia.22902, doi:10.1002/glia.22902. This article has 94 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1002/glia.22902)

[4. (Kagawa2020FABP7) Yoshiteru Kagawa, Banlanjo Abdulaziz Umaru, Hiroki Shima, Ryo Ito, Ryo Zama, Ariful Islam, Shin-ichiro Kanno, Akira Yasui, Shun Sato, Kosuke Jozaki, Subrata Kumar Shil, Hirofumi Miyazaki, Shuhei Kobayashi, Yui Yamamoto, Hiroshi Kogo, Chie Shimamoto-Mitsuyama, Akira Sugawara, Norihiro Sugino, Masayuki Kanamori, Teiji Tominaga, Takeo Yoshikawa, Kohji Fukunaga, Kazuhiko Igarashi, and Yuji Owada. Fabp7 regulates acetyl-coa metabolism through the interaction with acly in the nucleus of astrocytes. Molecular Neurobiology, 57(12):4891–4910, August 2020. URL: http://dx.doi.org/10.1007/s12035-020-02057-3, doi:10.1007/s12035-020-02057-3. This article has 15 citations and is from a peer-reviewed journal.](https://doi.org/10.1007/s12035-020-02057-3)

5. (Lenz2021FABP7) FABP7 Binds to Fatty Acid Micelles: Implications for Lipid Transport. This article has 1 citations.

[6. (Tripathi2016Docosahexaenoic) Sachin Tripathi, Rajesh Kushwaha, Juhi Mishra, Manoj Kumar Gupta, Harish Kumar, Somali Sanyal, Dhirendra Singh, Sabyasachi Sanyal, Amogh Anant Sahasrabuddhe, Mohan Kamthan, Mohana Krishna Reddy Mudiam, and Sanghamitra Bandyopadhyay. Docosahexaenoic acid up‐regulates both <scp>pi</scp>3k/<scp>akt</scp>‐dependent <scp>fabp</scp>7–<scp>ppar</scp>γ interaction and <scp>mkp</scp>3 that enhance <scp>gfap</scp> in developing rat brain astrocytes. Journal of Neurochemistry, 140(1):96–113, December 2016. URL: http://dx.doi.org/10.1111/jnc.13879, doi:10.1111/jnc.13879. This article has 38 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1111/jnc.13879)

[7. (Islam2019FABP7) Ariful Islam, Yoshiteru Kagawa, Hirofumi Miyazaki, Subrata Kumar Shil, Banlanjo A. Umaru, Yuki Yasumoto, Yui Yamamoto, and Yuji Owada. Fabp7 protects astrocytes against ros toxicity via lipid droplet formation. Molecular Neurobiology, 56(8):5763–5779, January 2019. URL: http://dx.doi.org/10.1007/s12035-019-1489-2, doi:10.1007/s12035-019-1489-2. This article has 53 citations and is from a peer-reviewed journal.](https://doi.org/10.1007/s12035-019-1489-2)

[8. (Goto2006A) Yasufumi Goto, Yuriko Matsuzaki, Sachiko Kurihara, Ayako Shimizu, Tsutomu Okada, Kazuhiko Yamamoto, Hiroshi Murata, Minoru Takata, Hiroyuki Aburatani, Dave S.B. Hoon, Toshiaki Saida, and Yutaka Kawakami. A new melanoma antigen fatty acid–binding protein 7, involved in proliferation and invasion, is a potential target for immunotherapy and molecular target therapy. Cancer Research, 66(8):4443–4449, April 2006. URL: http://dx.doi.org/10.1158/0008-5472.can-05-2505, doi:10.1158/0008-5472.can-05-2505. This article has 49 citations and is from a highest quality peer-reviewed journal.](https://doi.org/10.1158/0008-5472.can-05-2505)

[9. (Rademacher2002Solution) Martin Rademacher, Aukje W. Zimmerman, Heinz Rüterjans, Jacques H. Veerkamp, and Christian Lücke. Solution structure of fatty acid-binding protein from human brain, pages 61–68. Springer US, 2002. URL: http://dx.doi.org/10.1007/978-1-4419-9270-3_8, doi:10.1007/978-1-4419-9270-3_8. This article has 2 citations.](https://doi.org/10.1007/978-1-4419-9270-3_8)

[10. (Killoy2020FABP7) Kelby M. Killoy, Benjamin A. Harlan, Mariana Pehar, and Marcelo R. Vargas. <scp>fabp7</scp> upregulation induces a neurotoxic phenotype in astrocytes. Glia, 68(12):2693–2704, July 2020. URL: http://dx.doi.org/10.1002/glia.23879, doi:10.1002/glia.23879. This article has 42 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1002/glia.23879)

[11. (Iwayama2010Association) Yoshimi Iwayama, Eiji Hattori, Motoko Maekawa, Kazuo Yamada, Tomoko Toyota, Tetsuo Ohnishi, Yasuhide Iwata, Kenji J. Tsuchiya, Genichi Sugihara, Mitsuru Kikuchi, Kenji Hashimoto, Masaomi Iyo, Toshiya Inada, Hiroshi Kunugi, Norio Ozaki, Nakao Iwata, Shinichiro Nanko, Kazuya Iwamoto, Yuji Okazaki, Tadafumi Kato, and Takeo Yoshikawa. Association analyses between brain‐expressed fatty‐acid binding protein (fabp) genes and schizophrenia and bipolar disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 153B(2):484–493, February 2010. URL: http://dx.doi.org/10.1002/ajmg.b.31004, doi:10.1002/ajmg.b.31004. This article has 34 citations.](https://doi.org/10.1002/ajmg.b.31004)

[12. (Oeemig2009Backbone) Jesper S. Oeemig, Mathilde L. Jørgensen, Mikka S. Hansen, Evamaria I. Petersen, Laurent Duroux, and Reinhard Wimmer. Backbone and sidechain 1h, 13c and 15n resonance assignments of the human brain-type fatty acid binding protein (fabp7) in its apo form and the holo forms binding to dha, oleic acid, linoleic acid and elaidic acid. Biomolecular NMR Assignments, 3(1):89–93, March 2009. URL: http://dx.doi.org/10.1007/s12104-009-9148-6, doi:10.1007/s12104-009-9148-6. This article has 8 citations and is from a peer-reviewed journal.](https://doi.org/10.1007/s12104-009-9148-6)