STEAP3

This gene encodes a multipass membrane protein that functions as an iron transporter. The encoded protein can reduce both iron (Fe3+) and copper (Cu2+) cations. This protein may mediate downstream responses to p53, including promoting apoptosis. Deficiency in this gene can cause anemia. Alternative splicing results in multiple transcript variants.

Full Name

STEAP3 Metalloreductase

Function

Endosomal ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Participates in erythroid iron homeostasis by reducing Fe3+ to Fe2+. Can also reduce of Cu2+ to Cu1+, suggesting that it participates in copper homeostasis. Uses NADP+ as acceptor. May play a role downstream of p53/TP53 to interface apoptosis and cell cycle progression. Indirectly involved in exosome secretion by facilitating the secretion of proteins such as TCTP.

Biological Process

Biological Process apoptotic processIEA:UniProtKB-KW
Biological Process cell cycleIEA:UniProtKB-KW
Biological Process copper ion importManual Assertion Based On ExperimentIBA:GO_Central
Biological Process iron ion homeostasisIEA:UniProtKB-KW
Biological Process protein secretionManual Assertion Based On ExperimentIDA:MGI
Biological Process transferrin transportTAS:Reactome

Cellular Location

Endosome membrane
Localizes to vesicular-like structures at the plasma membrane and around the nucleus.

Involvement in disease

Anemia, hypochromic microcytic, with iron overload 2 (AHMIO2):
A hematologic disease characterized by abnormal hemoglobin content in the erythrocytes which are reduced in size, severe anemia, erythropoietic hyperplasia of bone marrow, massive hepatic iron deposition, and hepatosplenomegaly.

Topology

Cytoplasmic: 1-207
Helical: 208-228
Vesicular: 229-258
Helical: 259-279
Cytoplasmic: 280-304
Helical: 305-325
Vesicular: 326-358
Helical: 359-379
Cytoplasmic: 380-390
Helical: 391-411
Vesicular: 412-433
Helical: 434-454
Cytoplasmic: 455-488

PTM

Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced cleavage occurs at multiple sites in a glycosylation-independent manner.
Glycosylated.