. Author manuscript; available in PMC: 2022 Apr 11.

Published in final edited form as: Biochim Biophys Acta Mol Cell Res. 2020 Oct 19;1868(1):118890. doi: 10.1016/j.bbamcr.2020.118890

Table 1.

Main proteins involved in iron and/or Mn transport and trafficking.

Protein name (aliases)	Gene symbol	Subcellular localization	Primary metal substrate	Secondary metal substrate(s)	Function	Phenotypes of KO or mutant mice	Human disease and hallmarks of phenotype
Transferrin	TF	–	Fe³⁺	Mn³⁺	Plasma transport	Severe anemia; iron overload	Atransferrinemia. (OMIM 209300). Severe anemia, iron overload
Transferrin receptor 1	TFRC	Plasma membrane, endosome	–	–	Uptake	Embryonic lethal	–
DMT1 (Nramp2)	SLC11A2	Plasma membrane, endosome, lysosome	Fe²⁺	Mn²⁺	Uptake	Severe anemia	Anemia, hypochromic microcytic, iron overload (OMIM 206100)
Ferroportin	SLC40A1	Plasma membrane	Fe²⁺	Mn²⁺?	Export	Embryonic lethal	Hemochromatosis, Type 4; tissue iron overload (OMIM 606069)
DCYTB	CYBRD1	Plasma membrane	Fe³⁺	Cu²⁺	Uptake	None	–
Steap3	STEAP3	Endosome	Fe³⁺	Cu²⁺	Uptake	Moderate anemia	Anemia
Hephaestin	HEPH	Plasma membrane	Fe²⁺	Mn²⁺	Export	Microcytic anemia	–
Ceruloplasmin	CP	–	Fe²⁺	Mn²⁺	Export	Mild anemia	Aceruloplasminemia; iron overload (OMIM 604290)
PCBP1 PCBP2	PCBP1 PCBP2	Cytosolic	Fe²⁺	–	Cytosolic transport	Embryonic lethal; anemia	–
Mitoferrin 1 Mitoferrin 2	SLC25A37 SLC25A28	Inner mitochondrial membrane	Fe²⁺	Mn²⁺	Uptake	embryonic lethal; Inducible KO causes anemia	–
SLC39A14 (ZIP14)	SLC39A14	Plasma membrane, endosome, lysosome	Mn²⁺	Fe²⁺, Zn²⁺	Uptake	Mn overload except for liver; Impaired NTBI uptake	Hypermanganesemia with dystonia-2, HMNDYT2 (OMIM 617013). Brain Mn overload and parkinsonism
SLC39A8 (ZIP8)	SLC39A8	Plasma membrane, endosome, lysosome	Mn²⁺	Fe²⁺, Zn²⁺	Uptake	Embryonic lethal; Inducible KO results in Mn deficiency	Congenital disorder of glycosylation, type IIn (OMIM 616721); hypomanganesemia, skeletal abnormalities
SLC30A10 (ZnT10)	SLC30A10	Plasma membrane, Golgi, endosome	Mn²⁺	–	Export	Mn overload in all tissues	Hypermanganesemia with dystonia-1, HMNDYT1 (OMIM 613280)
ATP13A2 (Park9)	ATP13A2	Lysosome	Mn²⁺	Zn²⁺	Export	Increased sensitivity to Mn exposure	Kufor-Rakeb syndrome (OMIM 606693); juvenile- onset atypical Parkinson’s disease
TMEM165	TMEM165	Golgi	Ca²⁺	Mn²⁺	Export	Skeletal abnormalities; Impaired Ca, Mn transport into milk	Congenital disorder of glycosylation, type IIk (OMIM 614727); skeletal anomalies
SPCA1	ATP2C1	Golgi	Ca²⁺	Mn²⁺	Export	Impaired Ca transport into milk	Hailey-Hailey disease (OMIM 169600); blistering skin
LTCC	CACNA1C	Plasma membrane	Ca²⁺	Fe²⁺, Mn²⁺	Uptake	Embryonic lethal	Cardiac abnormalities; Timothy syndrome