Proteopedia

Engulfment and cell motility protein 1


Function

Engulfment and cell motility protein 1 (ELMO1) or CED-12 homolog mediates tumour progression by increasing cell motility and inhibiting apoptosis in human colorectal cancer[1]. Complex formation of ELMO1 with dedicator of cytokinesis 2 (DOCK2) is necessary for DOCK2-mediated Rac signaling[2].

Disease

Studies have shown that ELMO1 polymorphism is associated with diabetic nephropathy[3].

Structural highlights

The complex of ELMO1 and DOCK2 is formed between the C-terminal of ELMO1 and the SH3 domain of DOCK2. The which includes the binding , forms a five helix bundle with the DOCK2 SH3 domain[4].

3D structures of engulfment and cell motility protein 1

Updated on 04-May-2025

6jpp – hELMO1 RBD domain 1-113 – human - NMR

7y4a – hELMO1 RBD domain + RhoG
2vsz – hELMO1 PH domain 532-727
6tgb – hELMO1 + DOCK2 – Cryo EM
3a98 – hELMO1 PH domain + DOCK2
6tgc – hELMO1 + DOCK2 + Rac1 – Cryo EM
7dpa – hELMO1 + DOCK5 + Rac1 – Cryo EM
6uka – mELMO1 RBD domain + RhoG - mouse


Human SeMet ELMO1 C-terminal PH domain (green) complex with DOCK2 SH3 domain (cyan) (PDB code 3a98)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Park YL, Cho SB, Park SY, Oh HH, Myung E, Im CM, Son S, Kim S, Cho SY, Chung MW, Hong JY, Kim KH, Myung DS, Lee WS, Park D, Joo YE. Engulfment and Cell Motility 1 (ELMO1) Regulates Tumor Cell Behavior and Predicts Prognosis in Colorectal Cancer. Anticancer Res. 2022 Nov;42(11):5343-5355. PMID:36288887 doi:10.21873/anticanres.16058
  2. ↑ Chang L, Yang J, Jo CH, Boland A, Zhang Z, McLaughlin SH, Abu-Thuraia A, Killoran RC, Smith MJ, Côté JF, Barford D. Structure of the DOCK2-ELMO1 complex provides insights into regulation of the auto-inhibited state. Nat Commun. 2020 Jul 10;11(1):3464. PMID:32651375 doi:10.1038/s41467-020-17271-9
  3. ↑ Kakoki M, Bahnson EM, Hagaman JR, Siletzky RM, Grant R, Kayashima Y, Li F, Lee EY, Sun MT, Taylor JM, Rice JC, Almeida MF, Bahr BA, Jennette JC, Smithies O, Maeda-Smithies N. Engulfment and cell motility protein 1 potentiates diabetic cardiomyopathy via Rac-dependent and Rac-independent ROS production. JCI Insight. 2019 Jun 20;4(12):e127660. PMID:31217360 doi:10.1172/jci.insight.127660
  4. ↑ Hanawa-Suetsugu K, Kukimoto-Niino M, Mishima-Tsumagari C, Akasaka R, Ohsawa N, Sekine S, Ito T, Tochio N, Koshiba S, Kigawa T, Terada T, Shirouzu M, Nishikimi A, Uruno T, Katakai T, Kinashi T, Kohda D, Fukui Y, Yokoyama S. Structural basis for mutual relief of the Rac guanine nucleotide exchange factor DOCK2 and its partner ELMO1 from their autoinhibited forms. Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3305-10. Epub 2012 Feb 13. PMID:22331897 doi:10.1073/pnas.1113512109

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Michal Harel, Alexander Berchansky
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