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Protein

Metalloreductase STEAP3

Gene

STEAP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Cofactori

Protein has several cofactor binding sites:

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei36NADP1 Publication1
Binding sitei38NADP; via amide nitrogen1 Publication1
Binding sitei39NADP; via amide nitrogen1 Publication1
Binding sitei58NADP1 Publication1
Binding sitei59NADP1 Publication1
Binding sitei91NADP; via carbonyl oxygen1 Publication1
Binding sitei116NADP; via amide nitrogen1 Publication1
Binding sitei151NADP; via amide nitrogen1 Publication1
Metal bindingi316Iron (heme axial ligand)Curated1
Metal bindingi409Iron (heme axial ligand)Curated1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Apoptosis, Cell cycle, Ion transport, Iron transport, Transport

Keywords - Ligandi

Copper, FAD, Flavoprotein, Heme, Iron, Metal-binding, NADP

Enzyme and pathway databases

ReactomeiR-HSA-6803204. TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
R-HSA-917977. Transferrin endocytosis and recycling.

Protein family/group databases

TCDBi5.B.6.1.1. the transmembrane epithelial antigen protien-3 ferric reductase (steap) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloreductase STEAP3 (EC:1.16.1.-)
Alternative name(s):
Dudulin-2
Six-transmembrane epithelial antigen of prostate 3
Tumor suppressor-activated pathway protein 6
Short name:
hTSAP6
pHyde
Short name:
hpHyde
Gene namesi
Name:STEAP3
Synonyms:TSAP6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:24592. STEAP3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 207CytoplasmicSequence analysisAdd BLAST207
Transmembranei208 – 228HelicalSequence analysisAdd BLAST21
Topological domaini229 – 258VesicularSequence analysisAdd BLAST30
Transmembranei259 – 279HelicalSequence analysisAdd BLAST21
Topological domaini280 – 304CytoplasmicSequence analysisAdd BLAST25
Transmembranei305 – 325HelicalSequence analysisAdd BLAST21
Topological domaini326 – 358VesicularSequence analysisAdd BLAST33
Transmembranei359 – 379HelicalSequence analysisAdd BLAST21
Topological domaini380 – 390CytoplasmicSequence analysisAdd BLAST11
Transmembranei391 – 411HelicalSequence analysisAdd BLAST21
Topological domaini412 – 433VesicularSequence analysisAdd BLAST22
Transmembranei434 – 454HelicalSequence analysisAdd BLAST21
Topological domaini455 – 488CytoplasmicSequence analysisAdd BLAST34

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • endosome membrane Source: Reactome
  • integral component of plasma membrane Source: GO_Central
  • multivesicular body Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Anemia, hypochromic microcytic, with iron overload 2 (AHMIO2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615234

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi256N → I: Inhibits glycosylation and does not inhibit RHBDL4/RHBDD1-induced cleavage; when associated with A-344. 1 Publication1
Mutagenesisi325L → F: Strongly inhibits RHBDL4/RHBDD1-induced cleavage. 1 Publication1
Mutagenesisi344N → I: Inhibits glycosylation and does not inhibit RHBDL4/RHBDD1-induced cleavage; when associated with A-256. 1 Publication1

Organism-specific databases

DisGeNETi55240.
MalaCardsiSTEAP3.
MIMi615234. phenotype.
OpenTargetsiENSG00000115107.
Orphaneti300298. Severe congenital hypochromic anemia with ringed sideroblasts.
PharmGKBiPA142670863.

Polymorphism and mutation databases

BioMutaiSTEAP3.
DMDMi146325737.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002851711 – 488Metalloreductase STEAP3Add BLAST488

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei11PhosphoserineCombined sources1
Modified residuei17PhosphoserineCombined sources1
Modified residuei20PhosphoserineCombined sources1
Glycosylationi256N-linked (GlcNAc...)1 Publication1
Glycosylationi344N-linked (GlcNAc...)1 Publication1
Modified residuei474PhosphothreonineCombined sources1
Modified residuei486PhosphoserineCombined sources1

Post-translational modificationi

Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced cleavage occurs at multiple sites in a glycosylation-independent manner.1 Publication
Glycosylated.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei325 – 326Cleavage; by RHBDL4/RHBDD1Curated2

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ658P3.
MaxQBiQ658P3.
PaxDbiQ658P3.
PeptideAtlasiQ658P3.
PRIDEiQ658P3.

PTM databases

iPTMnetiQ658P3.
PhosphoSitePlusiQ658P3.
SwissPalmiQ658P3.

Expressioni

Tissue specificityi

Expressed in adult bone marrow, placenta, liver, skeletal muscle and pancreas. Down-regulated in hepatocellular carcinoma.3 Publications

Inductioni

By p53/TP53.1 Publication

Gene expression databases

BgeeiENSG00000115107.
ExpressionAtlasiQ658P3. baseline and differential.
GenevisibleiQ658P3. HS.

Organism-specific databases

HPAiHPA050510.

Interactioni

Subunit structurei

Homodimer. Interacts with BNIP3L, MYT1, RHBDL4/RHBDD1 and TCTP.4 Publications

Protein-protein interaction databases

BioGridi120533. 24 interactors.
IntActiQ658P3. 5 interactors.
STRINGi9606.ENSP00000376822.

Structurei

Secondary structure

1488
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi31 – 34Combined sources4
Helixi38 – 49Combined sources12
Beta strandi54 – 60Combined sources7
Helixi61 – 67Combined sources7
Beta strandi72 – 76Combined sources5
Helixi77 – 80Combined sources4
Beta strandi85 – 89Combined sources5
Helixi93 – 95Combined sources3
Helixi97 – 102Combined sources6
Helixi103 – 106Combined sources4
Beta strandi110 – 113Combined sources4
Helixi119 – 124Combined sources6
Helixi129 – 136Combined sources8
Beta strandi140 – 145Combined sources6
Helixi151 – 155Combined sources5
Beta strandi164 – 170Combined sources7
Helixi172 – 184Combined sources13
Beta strandi188 – 191Combined sources4
Helixi195 – 197Combined sources3
Helixi198 – 203Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VNSX-ray2.00A/B1-215[»]
2VQ3X-ray2.00A/B1-215[»]
ProteinModelPortaliQ658P3.
SMRiQ658P3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ658P3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini259 – 407Ferric oxidoreductaseAdd BLAST149

Sequence similaritiesi

Belongs to the STEAP family.Curated
Contains 1 ferric oxidoreductase domain.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF4F. Eukaryota.
COG2085. LUCA.
GeneTreeiENSGT00390000008042.
HOVERGENiHBG054379.
InParanoidiQ658P3.
KOiK10142.
OMAiGWKVPAL.
OrthoDBiEOG091G0F9X.
PhylomeDBiQ658P3.
TreeFamiTF332031.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR013130. Fe3_Rdtase_TM_dom.
IPR016040. NAD(P)-bd_dom.
IPR028939. ProC_N.
[Graphical view]
PfamiPF03807. F420_oxidored. 1 hit.
PF01794. Ferric_reduct. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q658P3-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MPEEMDKPLI SLHLVDSDSS LAKVPDEAPK VGILGSGDFA RSLATRLVGS
60 70 80 90 100
GFKVVVGSRN PKRTARLFPS AAQVTFQEEA VSSPEVIFVA VFREHYSSLC
110 120 130 140 150
SLSDQLAGKI LVDVSNPTEQ EHLQHRESNA EYLASLFPTC TVVKAFNVIS
160 170 180 190 200
AWTLQAGPRD GNRQVPICGD QPEAKRAVSE MALAMGFMPV DMGSLASAWE
210 220 230 240 250
VEAMPLRLLP AWKVPTLLAL GLFVCFYAYN FVRDVLQPYV QESQNKFFKL
260 270 280 290 300
PVSVVNTTLP CVAYVLLSLV YLPGVLAAAL QLRRGTKYQR FPDWLDHWLQ
310 320 330 340 350
HRKQIGLLSF FCAALHALYS FCLPLRRAHR YDLVNLAVKQ VLANKSHLWV
360 370 380 390 400
EEEVWRMEIY LSLGVLALGT LSLLAVTSLP SIANSLNWRE FSFVQSSLGF
410 420 430 440 450
VALVLSTLHT LTYGWTRAFE ESRYKFYLPP TFTLTLLVPC VVILAKALFL
460 470 480
LPCISRRLAR IRRGWEREST IKFTLPTDHA LAEKTSHV
Length:488
Mass (Da):54,601
Last modified:May 1, 2007 - v2
Checksum:iC89EB0D0430F9BFB
GO
Isoform 2 (identifier: Q658P3-2) [UniParc]FASTAAdd to basket

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

Show »
Length:498
Mass (Da):55,652
Checksum:i69DD201AA00C2D6B
GO
Isoform 3 (identifier: Q658P3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     351-351: Missing.

Show »
Length:487
Mass (Da):54,472
Checksum:i4A279EE7C8964412
GO
Isoform 4 (identifier: Q658P3-4) [UniParc]FASTAAdd to basket
Also known as: pHyde II

The sequence of this isoform differs from the canonical sequence as follows:
     351-351: Missing.
     396-488: SSLGFVALVL...HALAEKTSHV → CVATSSAGNT...GHQEDLSWTR

Show »
Length:456
Mass (Da):50,499
Checksum:i2ECEEB9C1515A9B7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti32G → S in AAL78206 (PubMed:10969787).Curated1
Sequence conflicti32G → S in AAM08128 (PubMed:10969787).Curated1
Sequence conflicti32G → S in AAM45136 (PubMed:14702039).Curated1
Sequence conflicti68F → Y in AAK50538 (Ref. 4) Curated1
Sequence conflicti68F → Y in BAA91839 (PubMed:17974005).Curated1
Sequence conflicti163R → G in AAL78206 (PubMed:10969787).Curated1
Sequence conflicti163R → G in AAM08128 (PubMed:10969787).Curated1
Sequence conflicti478D → G in CAD97986 (PubMed:15815621).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031975184A → T.Corresponds to variant rs17013371dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0248291M → MSHQPAVATKM in isoform 2. 2 Publications1
Alternative sequenceiVSP_024830351Missing in isoform 3 and isoform 4. 2 Publications1
Alternative sequenceiVSP_024831396 – 488SSLGF…KTSHV → CVATSSAGNTGSGTRRPESQ SQDPHLPAPHHQTSFLGPRS FCCSLVPVSTPYGHQEDLSW TR in isoform 4. 1 PublicationAdd BLAST93

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY214461 mRNA. Translation: AAO38238.1.
AF423424 mRNA. Translation: AAQ04065.1.
AF238864 mRNA. Translation: AAL78206.1.
AF262322 mRNA. Translation: AAM08128.1.
AY029585 mRNA. Translation: AAK50538.1.
AY082673 mRNA. Translation: AAM45136.1.
AK001691 mRNA. Translation: BAA91839.1.
AK291608 mRNA. Translation: BAF84297.1.
AL833624 mRNA. Translation: CAH56204.1.
BX538047 mRNA. Translation: CAD97986.1.
AC016673 Genomic DNA. Translation: AAX88963.1.
AC016736 Genomic DNA. Translation: AAY14872.1.
CH471103 Genomic DNA. Translation: EAW95209.1.
BC042150 mRNA. Translation: AAH42150.1.
BC095421 mRNA. Translation: AAH95421.2.
CCDSiCCDS2125.1. [Q658P3-1]
CCDS42738.1. [Q658P3-2]
RefSeqiNP_001008410.1. NM_001008410.1. [Q658P3-1]
NP_060704.2. NM_018234.2. [Q658P3-1]
NP_619543.2. NM_138637.2.
NP_878919.2. NM_182915.2. [Q658P3-2]
XP_006712677.1. XM_006712614.3. [Q658P3-1]
XP_006712678.1. XM_006712615.1. [Q658P3-1]
XP_011509705.1. XM_011511403.1. [Q658P3-1]
UniGeneiHs.647822.

Genome annotation databases

EnsembliENST00000393106; ENSP00000376818; ENSG00000115107. [Q658P3-1]
ENST00000393107; ENSP00000376819; ENSG00000115107. [Q658P3-1]
ENST00000393110; ENSP00000376822; ENSG00000115107. [Q658P3-2]
GeneIDi55240.
KEGGihsa:55240.
UCSCiuc002tlp.4. human. [Q658P3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY214461 mRNA. Translation: AAO38238.1.
AF423424 mRNA. Translation: AAQ04065.1.
AF238864 mRNA. Translation: AAL78206.1.
AF262322 mRNA. Translation: AAM08128.1.
AY029585 mRNA. Translation: AAK50538.1.
AY082673 mRNA. Translation: AAM45136.1.
AK001691 mRNA. Translation: BAA91839.1.
AK291608 mRNA. Translation: BAF84297.1.
AL833624 mRNA. Translation: CAH56204.1.
BX538047 mRNA. Translation: CAD97986.1.
AC016673 Genomic DNA. Translation: AAX88963.1.
AC016736 Genomic DNA. Translation: AAY14872.1.
CH471103 Genomic DNA. Translation: EAW95209.1.
BC042150 mRNA. Translation: AAH42150.1.
BC095421 mRNA. Translation: AAH95421.2.
CCDSiCCDS2125.1. [Q658P3-1]
CCDS42738.1. [Q658P3-2]
RefSeqiNP_001008410.1. NM_001008410.1. [Q658P3-1]
NP_060704.2. NM_018234.2. [Q658P3-1]
NP_619543.2. NM_138637.2.
NP_878919.2. NM_182915.2. [Q658P3-2]
XP_006712677.1. XM_006712614.3. [Q658P3-1]
XP_006712678.1. XM_006712615.1. [Q658P3-1]
XP_011509705.1. XM_011511403.1. [Q658P3-1]
UniGeneiHs.647822.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2VNSX-ray2.00A/B1-215[»]
2VQ3X-ray2.00A/B1-215[»]
ProteinModelPortaliQ658P3.
SMRiQ658P3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120533. 24 interactors.
IntActiQ658P3. 5 interactors.
STRINGi9606.ENSP00000376822.

Protein family/group databases

TCDBi5.B.6.1.1. the transmembrane epithelial antigen protien-3 ferric reductase (steap) family.

PTM databases

iPTMnetiQ658P3.
PhosphoSitePlusiQ658P3.
SwissPalmiQ658P3.

Polymorphism and mutation databases

BioMutaiSTEAP3.
DMDMi146325737.

Proteomic databases

EPDiQ658P3.
MaxQBiQ658P3.
PaxDbiQ658P3.
PeptideAtlasiQ658P3.
PRIDEiQ658P3.

Protocols and materials databases

DNASUi55240.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000393106; ENSP00000376818; ENSG00000115107. [Q658P3-1]
ENST00000393107; ENSP00000376819; ENSG00000115107. [Q658P3-1]
ENST00000393110; ENSP00000376822; ENSG00000115107. [Q658P3-2]
GeneIDi55240.
KEGGihsa:55240.
UCSCiuc002tlp.4. human. [Q658P3-1]

Organism-specific databases

CTDi55240.
DisGeNETi55240.
GeneCardsiSTEAP3.
HGNCiHGNC:24592. STEAP3.
HPAiHPA050510.
MalaCardsiSTEAP3.
MIMi609671. gene.
615234. phenotype.
neXtProtiNX_Q658P3.
OpenTargetsiENSG00000115107.
Orphaneti300298. Severe congenital hypochromic anemia with ringed sideroblasts.
PharmGKBiPA142670863.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF4F. Eukaryota.
COG2085. LUCA.
GeneTreeiENSGT00390000008042.
HOVERGENiHBG054379.
InParanoidiQ658P3.
KOiK10142.
OMAiGWKVPAL.
OrthoDBiEOG091G0F9X.
PhylomeDBiQ658P3.
TreeFamiTF332031.

Enzyme and pathway databases

ReactomeiR-HSA-6803204. TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
R-HSA-917977. Transferrin endocytosis and recycling.

Miscellaneous databases

ChiTaRSiSTEAP3. human.
EvolutionaryTraceiQ658P3.
GeneWikiiSTEAP3.
GenomeRNAii55240.
PROiQ658P3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115107.
ExpressionAtlasiQ658P3. baseline and differential.
GenevisibleiQ658P3. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR013130. Fe3_Rdtase_TM_dom.
IPR016040. NAD(P)-bd_dom.
IPR028939. ProC_N.
[Graphical view]
PfamiPF03807. F420_oxidored. 1 hit.
PF01794. Ferric_reduct. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiSTEA3_HUMAN
AccessioniPrimary (citable) accession number: Q658P3
Secondary accession number(s): A8K6E3
, Q4VBR2, Q4ZG36, Q53SQ8, Q7Z389, Q86SF6, Q8NEW6, Q8TDP3, Q8TF03, Q9NVB5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: May 1, 2007
Last modified: November 30, 2016
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Was initially thought to have tumor suppressor function in prostate cancer. However, it was shown that it is probably not the case (PubMed:12866033).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.