1.A.124.  The Small Mitochondrial Integral Membrane Protein (SMIM) Family 

The Vel blood group antigen is carried on the short extracellular segment of the 78-amino-acid-long, type II transmembrane protein SMIM1. Using cells expressing wild-type and mutant alleles of SMIM1, Kelley et al. 2019 demonstrated that dimerization of SMIM1 promotes cell surface display of the Vel epitope. SMIM1 dimerization is mediated both by an extracellular Cys77-dependent, homomeric disulfide linkage and a GxxxG helix-helix interaction motif in the transmembrane domain. These observations provide context for the observed variability in reactivity patterns of clinically important anti-Vel identified in patient sera. The MIM complex (composed by Mim1 and Mim2) is able to form ion-conducting channels in the outer mitochondria membrane (OMM) (Checchetto and Szabo 2018).



Checchetto, V. and I. Szabo. (2018). Novel Channels of the Outer Membrane of Mitochondria: Recent Discoveries Change Our View. Bioessays 40: e1700232.


TC#NameOrganismal TypeExample

The type II transmembrane protein, SMIM1, of 78 aas and 1 C-terminal TMS and SMIM2 of 85 aas with 1 TMS near the N-terminus of the protein. SMIM1 is the carrier of the Vel human blood group antigen (Kelley et al. 2019). Together with SMIM2 (MIM2), it forms the MIM complex, a heterodimeric ion channel (Checchetto and Szabo 2018).

Dimeric SMIM1/2 of Homo sapiens


The small integral membrane protein 1-like protein, SMIM1, of 73 aas and 1 TMS.

SIM1 of Neolamprologus brichardi


Small integral membrane protein 1, SMIM1, of 71 aas and 1 C-terminal TMS.

SMIM1 of Triplophysa tibetana


Small integral membrane protein 1, isoform X2, of 139 aas and 1 central TMS.

SMIM1 of Octodon degus (degu)


PilZ domain-containing protein of 126 aas and probably 1 central TMS.  Only the N-terminal segment shows sequence similarity with TC# 1.A.124.1.1.

PilZ domain protein of Bosea sp.


Uncharacterized protein of 208 aas and 1 TMS near the N-terminus of the protein.

UP of Priapulus caudatus


Small Mitochondrial Integral Membrane protein 2, SMIM2, of 122 aas and one TMS.

SMIM2 of Ictidomys tridecemlineatus (thirteen-lined ground squirrel)


Small mitochondrial integral membrane 2 (SMIM2) protein of 77 aas and 1 TMS near the N-terminus.

SMIM2 of Lontra canadensis (Northern American river otter)