Q8CI59 (STEA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metalloreductase STEAP3
EC=1.16.1.-

Alternative name(s):
Dudulin-2
Protein nm1054
Six-transmembrane epithelial antigen of prostate 3
Tumor suppressor-activated pathway protein 6

Gene names

Name:	Steap3
Synonyms:	Tsap6

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	488 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Endosomal ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Participates in erythroid iron homeostasis by reducing Fe3+ to Fe2+. Also mediates reduction 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. Ref.5 Ref.6
Cofactor	FAD Probable. Ref.5 NADP By similarity. Ref.5
Subunit structure	Homodimer. Interacts with BNIP3L, MYT1, RHBDL4/RHBDD1 and TCTP By similarity.
Subcellular location	Endosome membrane; Multi-pass membrane protein Ref.5.
Tissue specificity	Highly expressed in fetal liver (the site of midgestational hematopoiesis). Ref.1 Ref.5
Post-translational modification	Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced cleavage occurs at multiple sites in a glycosylation-independent manner By similarity. Glycosylated By similarity.
Disruption phenotype	Mice display iron deficiency anemia, due to a defect in iron release through the transferrin cycle. Ref.5
Sequence similarities	Belongs to the STEAP family. Contains 1 ferric oxidoreductase domain.
Sequence caution	The sequence AAK50539.1 differs from that shown. Reason: Frameshift at positions 171, 173 and 479.

Ontologies

Keywords
Biological process	Apoptosis Cell cycle Ion transport Iron transport Transport
Cellular component	Endosome Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Ligand	Copper FAD Flavoprotein Iron Metal-binding NADP
Molecular function	Oxidoreductase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cell cycle Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Inferred from electronic annotation. Source: Compara iron ion homeostasis Inferred from electronic annotation. Source: UniProtKB-KW iron ion transport Inferred from mutant phenotype Ref.5. Source: MGI protein secretion Inferred from sequence or structural similarity PubMed 22624035. Source: UniProtKB
Cellular_component	endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW multivesicular body Inferred from sequence alignment PubMed 15319436. Source: MGI plasma membrane Inferred from direct assay Ref.5. Source: MGI
Molecular_function	ferric-chelate reductase activity Inferred from direct assay Ref.5. Source: MGI metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8CI59-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8CI59-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAAEAHRQQGSCPTIPSEGCGKSPEKKGSAADSRPGTAM

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 488	488	Metalloreductase STEAP3		PRO_0000285172
Regions
	Topological domain	1 – 207	207	Cytoplasmic Potential
	Transmembrane	208 – 228	21	Helical; Potential
	Topological domain	229 – 258	30	Vesicular Potential
	Transmembrane	259 – 279	21	Helical; Potential
	Topological domain	280 – 304	25	Cytoplasmic Potential
	Transmembrane	305 – 325	21	Helical; Potential
	Topological domain	326 – 358	33	Vesicular Potential
	Transmembrane	359 – 379	21	Helical; Potential
	Topological domain	380 – 390	11	Cytoplasmic Potential
	Transmembrane	391 – 411	21	Helical; Potential
	Topological domain	412 – 433	22	Vesicular Potential
	Transmembrane	434 – 454	21	Helical; Potential
	Topological domain	455 – 488	34	Cytoplasmic Potential
	Domain	259 – 407	149	Ferric oxidoreductase
Sites
	Metal binding	316	1	Iron (heme axial ligand) Probable
	Metal binding	409	1	Iron (heme axial ligand) Probable
	Binding site	36	1	NADP By similarity
	Binding site	38	1	NADP; via amide nitrogen By similarity
	Binding site	39	1	NADP; via amide nitrogen By similarity
	Binding site	58	1	NADP By similarity
	Binding site	59	1	NADP By similarity
	Binding site	91	1	NADP; via carbonyl oxygen By similarity
	Binding site	116	1	NADP; via amide nitrogen By similarity
	Binding site	151	1	NADP; via amide nitrogen By similarity
	Site	325 – 326	2	Cleavage; by RHBDL4/RHBDD1 By similarity
Amino acid modifications
	Modified residue	17	1	Phosphoserine Ref.8 Ref.9
	Modified residue	20	1	Phosphoserine Ref.7 Ref.8 Ref.9 Ref.10
	Glycosylation	256	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1	1	M → MAAEAHRQQGSCPTIPSEGC GKSPEKKGSAADSRPGTAM in isoform 2.		VSP_024832
Experimental info
	Mutagenesis	316	1	H → L: Loss of function. Ref.5
	Mutagenesis	409	1	H → L: Loss of function. Ref.5
	Sequence conflict	81	1	V → M in BAC37383. Ref.3
	Sequence conflict	157	1	G → V in AAK50539. Ref.2
	Sequence conflict	169 – 172	4	SDQP → GNQQ in AAK50539. Ref.2
	Sequence conflict	176 – 179	4	RTIS → QRVM in AAK50539. Ref.2
	Sequence conflict	212	1	W → G in AAK50539. Ref.2
	Sequence conflict	350	1	V → A in BAC37383. Ref.3
	Sequence conflict	350	1	V → A in BAE39201. Ref.3
	Sequence conflict	455	1	S → N in BAC37383. Ref.3
	Sequence conflict	455	1	S → N in BAE39201. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 9A08D99C90CF83F4	FASTA	488	54,749
	10 20 30 40 50 60 MSGEMDKPLI SRRLVDSDGS LAEVPKEAPK VGILGSGDFA RSLATRLVGS GFSVVVGSRN 70 80 90 100 110 120 PKRTAGLFPS LAQVTFQEEA VSSPEVIFVA VFREHYSSLC SLADQLAGKI LVDVSNPTEK 130 140 150 160 170 180 EHLQHRQSNA EYLASLFPAC TVVKAFNVIS AWALQAGPRD GNRQVLICSD QPEAKRTISE 190 200 210 220 230 240 MARAMGFTPL DMGSLASARE VEAIPLRLLP SWKVPTLLAL GLFVCFYTYN FIRDVLQPYI 250 260 270 280 290 300 RKDENKFYKM PLSVVNTTLP CVAYVLLSLV YLPGVLAAAL QLRRGTKYQR FPDWLDHWLQ 310 320 330 340 350 360 HRKQIGLLSF FFAMLHALYS FCLPLRRSHR YDLVNLAVKQ VLANKSRLWV EEEVWRMEIY 370 380 390 400 410 420 LSLGVLALGM LSLLAVTSLP SIANSLNWKE FSFVQSTLGF VALILSTMHT LTYGWTRAFE 430 440 450 460 470 480 ENHYKFYLPP TFTLTLLLPC VIILAKGLFL LPCLSRRLTK IRRGWEKDGA VKFMLPGDHT QGEKTSHV
	Isoform 2 [UniParc]. Checksum: 6306CD717E25200A	FASTA	526	58,530
	10 20 30 40 50 60 MAAEAHRQQG SCPTIPSEGC GKSPEKKGSA ADSRPGTAMS GEMDKPLISR RLVDSDGSLA 70 80 90 100 110 120 EVPKEAPKVG ILGSGDFARS LATRLVGSGF SVVVGSRNPK RTAGLFPSLA QVTFQEEAVS 130 140 150 160 170 180 SPEVIFVAVF REHYSSLCSL ADQLAGKILV DVSNPTEKEH LQHRQSNAEY LASLFPACTV 190 200 210 220 230 240 VKAFNVISAW ALQAGPRDGN RQVLICSDQP EAKRTISEMA RAMGFTPLDM GSLASAREVE 250 260 270 280 290 300 AIPLRLLPSW KVPTLLALGL FVCFYTYNFI RDVLQPYIRK DENKFYKMPL SVVNTTLPCV 310 320 330 340 350 360 AYVLLSLVYL PGVLAAALQL RRGTKYQRFP DWLDHWLQHR KQIGLLSFFF AMLHALYSFC 370 380 390 400 410 420 LPLRRSHRYD LVNLAVKQVL ANKSRLWVEE EVWRMEIYLS LGVLALGMLS LLAVTSLPSI 430 440 450 460 470 480 ANSLNWKEFS FVQSTLGFVA LILSTMHTLT YGWTRAFEEN HYKFYLPPTF TLTLLLPCVI 490 500 510 520 ILAKGLFLLP CLSRRLTKIR RGWEKDGAVK FMLPGDHTQG EKTSHV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase." Passer B.J., Nancy-Portebois V., Amzallag N., Prieur S., Cans C., Roborel de Climens A., Fiucci G., Bouvard V., Tuynder M., Susini L., Morchoisne S., Crible V., Lespagnol A., Dausset J., Oren M., Amson R., Telerman A. Proc. Natl. Acad. Sci. U.S.A. 100:2284-2289(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
[2]	Serru V., Lamblin D., Lenoir C., Manivet P., Vaubourdolle M., Kellermann O., Loric S. Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J and NOD. Tissue: Testis.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: Czech II. Tissue: Mammary tumor.
[5]	"Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells." Ohgami R.S., Campagna D.R., Greer E.L., Antiochos B., McDonald A., Chen J., Sharp J.J., Fujiwara Y., Barker J.E., Fleming M.D. Nat. Genet. 37:1264-1269(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, HEME-BINDING, COFACTOR, TISSUE SPECIFICITY, MUTAGENESIS OF HIS-316 AND HIS-409.
[6]	"The Steap proteins are metalloreductases." Ohgami R.S., Campagna D.R., McDonald A., Fleming M.D. Blood 108:1388-1394(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17 AND SER-20, MASS SPECTROMETRY. Tissue: Melanoma.
[9]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17 AND SER-20, MASS SPECTROMETRY. Tissue: Macrophage.
[10]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY214462 mRNA. Translation: AAO38239.1. AY029586 mRNA. Translation: AAK50539.1. Frameshift. AK078769 mRNA. Translation: BAC37383.1. AK167028 mRNA. Translation: BAE39201.1. AK171237 mRNA. Translation: BAE42333.1. BC037435 mRNA. Translation: AAH37435.1.
IPI	IPI00330941. IPI00990735.
RefSeq	NP_001078878.1. NM_001085409.1. NP_573449.2. NM_133186.3.
UniGene	Mm.181033.
3D structure databases
ProteinModelPortal	Q8CI59.
SMR	Q8CI59. Positions 29-209.
ModBase	Search...
PTM databases
PhosphoSite	Q8CI59.
Proteomic databases
PaxDb	Q8CI59.
PRIDE	Q8CI59.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000112639; ENSMUSP00000108258; ENSMUSG00000026389. ENSMUST00000112640; ENSMUSP00000108259; ENSMUSG00000026389. ENSMUST00000112641; ENSMUSP00000108260; ENSMUSG00000026389.
GeneID	68428.
KEGG	mmu:68428.
Organism-specific databases
CTD	55240.
MGI	MGI:1915678. Steap3.
Phylogenomic databases
eggNOG	COG2085.
GeneTree	ENSGT00390000008042.
HOGENOM	HOG000234491.
HOVERGEN	HBG054379.
InParanoid	Q8CI59.
KO	K10142.
OrthoDB	EOG412M5Q.
Gene expression databases
ArrayExpress	Q8CI59.
Bgee	Q8CI59.
CleanEx	MM_STEAP3.
Genevestigator	Q8CI59.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
InterPro	IPR013130. Fe3_Rdtase_TM_dom. IPR016040. NAD(P)-bd_dom. IPR004455. NADP_OxRdtase_F420. [Graphical view]
Pfam	PF03807. F420_oxidored. 1 hit. PF01794. Ferric_reduct. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	327158.
SOURCE	Search...

Entry information

Entry name

STEA3_MOUSE

Accession

Primary (citable) accession number: Q8CI59
Secondary accession number(s): Q3TKE4 , Q80ZF3, Q8C5F0, Q924Z1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 2007
Last sequence update:	March 1, 2003
Last modified:	April 3, 2013
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program