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Q8CI59 (STEA3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length488 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processApoptosis
Cell cycle
Ion transport
Iron transport
Transport
   Cellular componentEndosome
Membrane
   Coding sequence diversityAlternative splicing
   DomainTransmembrane
Transmembrane helix
   LigandCopper
FAD
Flavoprotein
Iron
Metal-binding
NADP
   Molecular functionOxidoreductase
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

copper ion import

Inferred from direct assay Ref.6. Source: MGI

exosomal secretion

Inferred from mutant phenotype PubMed 18617898. Source: MGI

ferric iron import into cell

Inferred from direct assay Ref.6. Source: MGI

iron ion homeostasis

Inferred from electronic annotation. Source: UniProtKB-KW

iron ion transport

Inferred from mutant phenotype Ref.5. Source: MGI

oxidation-reduction process

Inferred from direct assay Ref.6. Source: MGI

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from mutant phenotype PubMed 18617898. Source: MGI

protein secretion

Inferred from sequence or structural similarity PubMed 22624035. Source: UniProtKB

   Cellular_componentendosome

Inferred from direct assay Ref.5. Source: MGI

endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of 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.5PubMed 18955558. Source: MGI

   Molecular_functioncupric reductase activity

Inferred from direct assay Ref.6. Source: MGI

ferric-chelate reductase (NADPH) activity

Inferred from direct assay Ref.6. Source: MGI

ferric-chelate reductase activity

Inferred from direct assay Ref.5. Source: MGI

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 488488Metalloreductase STEAP3
PRO_0000285172

Regions

Topological domain1 – 207207Cytoplasmic Potential
Transmembrane208 – 22821Helical; Potential
Topological domain229 – 25830Vesicular Potential
Transmembrane259 – 27921Helical; Potential
Topological domain280 – 30425Cytoplasmic Potential
Transmembrane305 – 32521Helical; Potential
Topological domain326 – 35833Vesicular Potential
Transmembrane359 – 37921Helical; Potential
Topological domain380 – 39011Cytoplasmic Potential
Transmembrane391 – 41121Helical; Potential
Topological domain412 – 43322Vesicular Potential
Transmembrane434 – 45421Helical; Potential
Topological domain455 – 48834Cytoplasmic Potential
Domain259 – 407149Ferric oxidoreductase

Sites

Metal binding3161Iron (heme axial ligand) Probable
Metal binding4091Iron (heme axial ligand) Probable
Binding site361NADP By similarity
Binding site381NADP; via amide nitrogen By similarity
Binding site391NADP; via amide nitrogen By similarity
Binding site581NADP By similarity
Binding site591NADP By similarity
Binding site911NADP; via carbonyl oxygen By similarity
Binding site1161NADP; via amide nitrogen By similarity
Binding site1511NADP; via amide nitrogen By similarity
Site325 – 3262Cleavage; by RHBDL4/RHBDD1 By similarity

Amino acid modifications

Modified residue171Phosphoserine Ref.8
Modified residue201Phosphoserine Ref.7 Ref.8
Glycosylation2561N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence11M → MAAEAHRQQGSCPTIPSEGC GKSPEKKGSAADSRPGTAM in isoform 2.
VSP_024832

Experimental info

Mutagenesis3161H → L: Loss of function. Ref.5
Mutagenesis4091H → L: Loss of function. Ref.5
Sequence conflict811V → M in BAC37383. Ref.3
Sequence conflict1571G → V in AAK50539. Ref.2
Sequence conflict169 – 1724SDQP → GNQQ in AAK50539. Ref.2
Sequence conflict176 – 1794RTIS → QRVM in AAK50539. Ref.2
Sequence conflict2121W → G in AAK50539. Ref.2
Sequence conflict3501V → A in BAC37383. Ref.3
Sequence conflict3501V → A in BAE39201. Ref.3
Sequence conflict4551S → N in BAC37383. Ref.3
Sequence conflict4551S → N in BAE39201. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 9A08D99C90CF83F4

FASTA48854,749
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 6306CD717E25200A
Show »

FASTA52658,530

References

« Hide '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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[8]"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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+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.
RefSeqNP_001078878.1. NM_001085409.1.
NP_573449.2. NM_133186.3.
UniGeneMm.181033.

3D structure databases

ProteinModelPortalQ8CI59.
SMRQ8CI59. Positions 29-209.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ8CI59.

Proteomic databases

PaxDbQ8CI59.
PRIDEQ8CI59.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000112639; ENSMUSP00000108258; ENSMUSG00000026389.
ENSMUST00000112640; ENSMUSP00000108259; ENSMUSG00000026389.
ENSMUST00000112641; ENSMUSP00000108260; ENSMUSG00000026389.
GeneID68428.
KEGGmmu:68428.

Organism-specific databases

CTD55240.
MGIMGI:1915678. Steap3.

Phylogenomic databases

eggNOGCOG2085.
GeneTreeENSGT00390000008042.
HOGENOMHOG000234491.
HOVERGENHBG054379.
InParanoidQ8CI59.
KOK10142.
PhylomeDBQ8CI59.
TreeFamTF332031.

Gene expression databases

ArrayExpressQ8CI59.
BgeeQ8CI59.
CleanExMM_STEAP3.
GenevestigatorQ8CI59.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR013130. Fe3_Rdtase_TM_dom.
IPR016040. NAD(P)-bd_dom.
IPR028939. ProC_N.
[Graphical view]
PfamPF03807. F420_oxidored. 1 hit.
PF01794. Ferric_reduct. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio327158.
PROQ8CI59.
SOURCESearch...

Entry information

Entry nameSTEA3_MOUSE
AccessionPrimary (citable) accession number: Q8CI59
Secondary accession number(s): Q3TKE4 expand/collapse secondary AC list , Q80ZF3, Q8C5F0, Q924Z1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: March 1, 2003
Last modified: April 16, 2014
This is version 90 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot