8.B.27 The Na+K+-ATPase Beta-Subunit-Interacting NKAIN (NKAIN) Family 

Gorokhova et al. 2007 characterized a family consisting of four mammalian proteins (NKAIN1, 2, 3 and 4) and a single Drosophila ortholog dNKAIN with two well conserved N-terminal TMSs. NKAIN family members are neuronally expressed in multiple regions of the mouse brain, although their expression is not ubiquitous. Mouse NKAIN1 interacts with the beta1 subunit of the Na,K-ATPase, whereas the Drosophila ortholog dNKAIN interacts with Nrv2.2, a Drosophila homolog of the Na,K-ATPase beta subunits. NKAIN1 can form a complex with another beta subunit-binding protein, MONaKA, when binding to the beta1 subunit of the Na,K-ATPase. A complex between mammalian NKAIN1 and MONaKA may be required for NKAIN function. This hypothesis is supported by the fact that dNKAIN, but not NKAIN1, induces voltage-independent amiloride-insensitive Na+-specific conductance that can be blocked by lanthanum. Drosophila mutants with decreased dNKAIN expression exhibit temperature-sensitive paralysis, a phenotype also caused by mutations in the Na,K-ATPase α-subunit and several ion channels. The neuronal expression of NKAIN proteins, their membrane localization and the temperature-sensitive paralysis of NKAIN Drosophila mutants strongly suggest that this protein family may be critical for neuronal function (Gorokhova et al. 2007).

This family belongs to the .



Gorokhova, S., S. Bibert, K. Geering, and N. Heintz. (2007). A novel family of transmembrane proteins interacting with beta subunits of the Na,K-ATPase. Hum Mol Genet 16: 2394-2410.

Zuo, L., K. Wang, X.Y. Zhang, J.H. Krystal, C.S. Li, F. Zhang, H. Zhang, and X. Luo. (2013). NKAIN1-SERINC2 is a functional, replicable and genome-wide significant risk gene region specific for alcohol dependence in subjects of European descent. Drug Alcohol Depend 129: 254-264.


TC#NameOrganismal TypeExample

dNKAIN of 658 aas and 4 N-terminal TMSs.  It Induces a small but significant sodium conductance when expressed in Xenopus oocytes (Gorokhova et al. 2007).

NKAIN of Drosophila melanogaster


Na+/K+-transporting ATPase subunit beta-1-interacting protein 1, NKAIN1 or SERINC2 of 207 aas.  NKAIN1-SERINC2 may harbor one or more causal variants for alcohol dependence which may contribute to the disease risk by way of neurotransmitter systems or metabolic pathways (Zuo et al. 2013).

NKAIN1 of Homo sapiens


NKAIN2 of 208 aas and 4 TMSs.  70% identical to NKAIN1.

NKAIN2 of Homo sapiens


NKAIN3 of 197 aas and 4 or 5 putative TMSs.

NKAIN3 of Homo sapiens


NKAIN4 of 208 aas and 5 TMSs.

NKAIN4 of Homo sapiens