Article · Wikipedia archive · Last revised May 31, 2026

NELL2

Protein kinase C-binding protein NELL2 is a secreted glycoprotein that in humans is encoded by the NELL2 gene. It is a homolog of Nel, which is a gene present in the neural tissues of chickens.

Last revised
May 31, 2026
Read time
≈ 4 min
Length
966 w
Citations
19
Source
NELL2
Identifiers
AliasesNELL2, NRP2, neural EGFL like 2
External IDsOMIM: 602320; MGI: 1858510; HomoloGene: 4488; GeneCards: NELL2; OMA:NELL2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001145107
NM_001145108
NM_001145109
NM_001145110
NM_006159

NM_001289653
NM_016743
NM_001356950
NM_001356951

RefSeq (protein)

NP_001138579
NP_001138580
NP_001138581
NP_001138582
NP_006150

NP_001276582
NP_001343879
NP_001343880

Location (UCSC)Chr 12: 44.51 – 44.92 MbChr 15: 94.97 – 95.43 Mb
PubMed search34
Wikidata
View/Edit HumanView/Edit Mouse

Protein kinase C-binding protein NELL2 is a secreted glycoprotein that in humans is encoded by the NELL2 gene.5 It is a homolog of Nel, which is a gene present in the neural tissues of chickens.6

This gene encodes a cytoplasmic protein that contains six epidermal growth factor (EGF) -like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. An alternative splice variant has been described but its full length sequence has not been determined.5

Function

NELL2 has been implicated to be involved in a variety of different functions including neuronal development, sperm maturation, cancer progression and bone development.78910

NELL2 has been shown to have roles in neuronal polarization and axon growth.11 NELL2 is a negative regulator of axon guidance in the SLIT-ROBO signalling pathway where it binds with the ROBO3/Rig-1 receptor.12 It can also bind with ROBO2 under acidic conditions, where ROBO2 undergoes proteolytic cleavage.8

NELL2 expression has been linked to higher survival rates for female lung adenocarcinoma patients.13

References

References

  1. GRCh38: Ensembl release 89: ENSG00000184613Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000022454Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: NELL2 NEL-like 2 (chicken)".
  6. Watanabe, Takeshi K.; Katagiri, Toyomasa; Suzuki, Mikio; Shimizu, Fumio; Fujiwara, Tsutomu; Kanemoto, Naohide; Nakamura, Yusuke; Hirai, Yoshikatsu; Maekawa, Hiroumi; Takahashi, Ei-ichi (1996-12-15). "Cloning and Characterization of Two Novel Human cDNAs (NELL1 and NELL2) Encoding Proteins with Six EGF-like Repeats". Genomics. 38 (3): 273–276. doi:10.1006/geno.1996.0628. ISSN 0888-7543.
  7. Miyaguchi, Masaki; Nakanishi, Yoichi; Maturana, Andrés D.; Mizutani, Kimihiko; Niimi, Tomoaki (2022-10-15). "Conformational Change of the Hairpin-like-structured Robo2 Ectodomain Allows NELL1/2 Binding". Journal of Molecular Biology. 434 (19) 167777. doi:10.1016/j.jmb.2022.167777. ISSN 0022-2836.
  8. Yamamoto, Naoka; Kashiwagi, Manabu; Ishihara, Manami; Kojima, Takaaki; Maturana, Andrés D.; Kuroda, Shun'ichi; Niimi, Tomoaki (2019-03-22). "Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/2". Journal of Biological Chemistry. 294 (12): 4693–4703. doi:10.1074/jbc.RA118.005819. ISSN 0021-9258. PMC 6433047. PMID 30700556.
  9. Yuan, Hairui; Wang, Xinyu; Du, Shuanglin; Li, Mengyue; Zhu, Endong; Zhou, Jie; Dong, Yuan; Wang, Shuang; Shan, Liying; Liu, Qian; Wang, Baoli (2025-04-11). "NELL2, a novel osteoinductive factor, regulates osteoblast differentiation and bone homeostasis through fibronectin 1/integrin-mediated FAK/AKT signaling". Bone Research. 13 (1): 46. doi:10.1038/s41413-025-00420-5. ISSN 2095-6231. PMC 11986068. PMID 40210857.
  10. Kiyozumi, Daiji; Noda, Taichi; Yamaguchi, Ryo; Tobita, Tomohiro; Matsumura, Takafumi; Shimada, Kentaro; Kodani, Mayo; Kohda, Takashi; Fujihara, Yoshitaka; Ozawa, Manabu; Yu, Zhifeng; Miklossy, Gabriella; Bohren, Kurt M.; Horie, Masato; Okabe, Masaru (2020-06-05). "NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility". Science. 368 (6495): 1132–1135. Bibcode:2020Sci...368.1132K. doi:10.1126/science.aay5134. PMC 7396227. PMID 32499443.
  11. Kim, Han Rae; Kim, Dong Hee; An, Ji Young; Kang, Dasol; Park, Jeong Woo; Hwang, Eun Mi; Seo, Eun Jin; Jang, Il Ho; Ha, Chang Man; Lee, Byung Ju (2020-06-30). "NELL2 Function in Axon Development of Hippocampal Neurons". Molecules and Cells. 43 (6): 581–589. doi:10.14348/molcells.2020.0032. ISSN 0219-1032. PMC 7332358. PMID 32597395.
  12. Jaworski, Alexander; Tom, Irene; Tong, Raymond K.; Gildea, Holly K.; Koch, Alexander W.; Gonzalez, Lino C.; Tessier-Lavigne, Marc (2015-11-20). "Operational redundancy in axon guidance through the multifunctional receptor Robo3 and its ligand NELL2". Science. 350 (6263): 961–965. doi:10.1126/science.aad2615.
  13. "Research update from the MCM team (October 2025)". World Community Grid. 28 October 2025. Retrieved 29 October 2025.
Further reading

Further reading