9.B.417. The MCFD2/LMAN1 Complex Receptor (MLM-CR) Family LMAN ( a mannose-specific lectin, Ergic-53; 510 aas with two TMSs, N- and C-terminal) and MCFD2 of 146 aas and one N-terminal TMS, form a complex that recognizes sugar residues of glycoproteins, glycolipids, or glycosylphosphatidyl inositol anchors, It may be involved in the sorting and/or recycling of proteins, lipids, or both. The LMAN1-MCFD2 complex forms a specific cargo receptor for the ER-to-Golgi transport of selected proteins (Nufer et al. 2003; Zhang et al. 2003). It plays a role in the secretion of coagulation factors. A 1.60 Å resolution crystal structure of the ERGIC-53(CRD)-MCFD2 complex is available showing that MCFD2, but not ERGIC-53-CRD, exhibits conformational plasticity that may be relevant to its accommodation of various polypeptide ligands (Satoh et al. 2020). The LMAN1-MCFD2 complex is a cargo receptor for the ER-Golgi transport of alpha1-antitrypsin (Zhang et al. 2022).
References:
Lamothe, S.M., D. Das, A.A. Wong, Y. Hao, A.D. Maguire, B.J. Kerr, V.A. Baronas, and H.T. Kurata. (2024). Regulation of Kv1.2 Redox-Sensitive Gating by the Transmembrane Lectin LMAN2. Function (Oxf) 5:.
Nufer, O., F. Kappeler, S. Guldbrandsen, and H.P. Hauri. (2003). ER export of ERGIC-53 is controlled by cooperation of targeting determinants in all three of its domains. J Cell Sci 116: 4429-4440.
Satoh, T., M. Nishio, K. Suzuki, M. Yagi-Utsumi, Y. Kamiya, T. Mizushima, and K. Kato. (2020). Crystallographic snapshots of the EF-hand protein MCFD2 complexed with the intracellular lectin ERGIC-53 involved in glycoprotein transport. Acta Crystallogr F Struct Biol Commun 76: 216-221.
Zhang, B., M.A. Cunningham, W.C. Nichols, J.A. Bernat, U. Seligsohn, S.W. Pipe, J.H. McVey, U. Schulte-Overberg, N.B. de Bosch, A. Ruiz-Saez, G.C. White, E.G. Tuddenham, R.J. Kaufman, and D. Ginsburg. (2003). Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat. Genet. 34: 220-225.
Zhang, D., L. Ye, S. Hu, Q. Zhu, C. Li, and C. Zhu. (2022). Comprehensive Analysis of the Expression and Prognostic Value of LMAN2 in HER2+ Breast Cancer. J Immunol Res 2022: 7623654.
Zhang, Y., M. Zhu, C. Zheng, W. Wei, B.T. Emmer, and B. Zhang. (2022). LMAN1-MCFD2 complex is a cargo receptor for the ER-Golgi transport of α1-antitrypsin. Biochem. J. 479: 839-855.
Examples:
TC#	Name	Organismal Type	Example
9.B.417.1.1	The MCFD2/LMAN1 Complex Receptor (MLM-CR) involved in glycoprotein and glycolipid trafficking between the ER and golgi (Satoh et al. 2020). MCFD2 has a C-terminal domain of ~50% of the protein that is distantly related to members of TC family 8.A.82.		Protein receptor of Homo sapiens

9.B.417.1.2	LMAN2 or VIP36 (GP36B, C5orf8) of 356 aas and 2 TMSs, N- and C-terminal. It plays a role as an intracellular lectin in the early secretory pathway and interacts with N-acetyl-D-galactosamine and high-mannose type glycans as well as O-linked glycans. It is involved in the transport and sorting of glycoproteins carrying high mannose-type glycans. LMAN2 expression had a positive link to breast cancer stemness, proliferation, metastasis, and differentiation (Zhang et al. 2022).It also regulates Kv1.2 (TC# 1.A.1.2.10) redox-sensitive gating (Lamothe et al. 2024).		LMAN2 of Homo sapiens

9.B.417.1.3	Uncharacterized protein of 453 aas and 2 TMSs, N- and C-terminal.		UP of Pyrenophora teres

9.B.417.1.4	Legume-like lectin family-domain-containing protein of 395 aas and one C-terminal TMS and possibly one N-terminal TMS as well.		Lectin of Tribonema minus

9.B.417.1.5	T9SS type B sorting domain-containing protein of 757 aas and 2 TMSs, N- and C-terminal.		T9SS protein of Chryseobacterium scophthalmum

9.B.417.1.6	Lectin family glycoprotein receptor of 408 aas and 2 TMSs, N- and C-terminal.		Lectin glycoprotein of Schizosaccharomyces japonicus

9.B.417.1.7	Uncharacterized protein of 469 aas and 2 TMSs, N- and C-terminal.		UP of Cryptosporidium hominis