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Protein

Metalloreductase STEAP4

Gene

STEAP4

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

Functioni

Metalloreductase that has the ability to reduce both Fe3+ to Fe2+ and Cu2+ to Cu1+ (By similarity). Uses NADP+ as acceptor (By similarity). Plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses (By similarity). Associated with obesity and insulin-resistance (PubMed:18430367, PubMed:18381574). Involved in inflammatory arthritis, through the regulation of inflammatory cytokines (PubMed:19660107). Inhibits anchorage-independent cell proliferation (PubMed:19787193).By similarity4 Publications

Cofactori

FADBy similarityNote: Can also utilize the flavins FMN and riboflavin.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei67NADPBy similarity1
Binding sitei106NADP; via amide nitrogenBy similarity1
Binding sitei139NADP; via amide nitrogenBy similarity1
Binding sitei171NADPBy similarity1
Metal bindingi304Iron (heme axial ligand)By similarity1
Metal bindingi397Iron (heme axial ligand)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi27 – 30NADPBy similarity4
Nucleotide bindingi49 – 50NADPBy similarity2
Nucleotide bindingi81 – 85NADPBy similarity5

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processIon transport, Iron transport, Transport
LigandCopper, FAD, Flavoprotein, Heme, Iron, Metal-binding, NAD, NADP

Protein family/group databases

TCDBi5.B.6.1.3. the transmembrane epithelial antigen protien-3 ferric reductase (steap) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloreductase STEAP4 (EC:1.16.1.-)
Alternative name(s):
Six-transmembrane epithelial antigen of prostate 4
SixTransMembrane protein of prostate 2
Tumor necrosis factor, alpha-induced protein 9
Gene namesi
Name:STEAP4
Synonyms:STAMP2, TNFAIP9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000127954.12.
HGNCiHGNC:21923. STEAP4.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei196 – 216HelicalSequence analysisAdd BLAST21
Transmembranei246 – 266HelicalSequence analysisAdd BLAST21
Transmembranei293 – 313HelicalSequence analysisAdd BLAST21
Transmembranei348 – 368HelicalSequence analysisAdd BLAST21
Transmembranei381 – 401HelicalSequence analysisAdd BLAST21
Transmembranei419 – 439HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi79689.
OpenTargetsiENSG00000127954.
PharmGKBiPA134874572.

Polymorphism and mutation databases

BioMutaiSTEAP4.
DMDMi74748242.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002851741 – 459Metalloreductase STEAP4Add BLAST459

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi323N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ687X5.
MaxQBiQ687X5.
PaxDbiQ687X5.
PeptideAtlasiQ687X5.
PRIDEiQ687X5.

PTM databases

iPTMnetiQ687X5.
PhosphoSitePlusiQ687X5.

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in adipose tissue. Expressed in placenta, lung, heart and prostate. Detected at lower levels in liver, skeletal muscle, pancreas, testis and small intestine. Highly expressed in joints of patients with rheumatoid arthritis and localized with CD68 cells, a marker for macrophages.6 Publications

Inductioni

By TNF and IL1B/interleukin-1 beta in adipose tissue. Up-regulated by androgens, including testosterone and dihydrotestosterone (DHT).3 Publications

Gene expression databases

BgeeiENSG00000127954.
CleanExiHS_STEAP4.
ExpressionAtlasiQ687X5. baseline and differential.
GenevisibleiQ687X5. HS.

Organism-specific databases

HPAiHPA075871.

Interactioni

Subunit structurei

Homodimer (By similarity). Interacts with PTK2/FAK1; the interaction may regulate PTK2 phosphorylation.By similarity1 Publication

Protein-protein interaction databases

BioGridi122810. 2 interactors.
IntActiQ687X5. 1 interactor.
STRINGi9606.ENSP00000369419.

Structurei

3D structure databases

ProteinModelPortaliQ687X5.
SMRiQ687X5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini247 – 395Ferric oxidoreductaseSequence analysisAdd BLAST149

Sequence similaritiesi

Belongs to the STEAP family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF4F. Eukaryota.
COG2085. LUCA.
GeneTreeiENSGT00390000008042.
HOGENOMiHOG000234491.
HOVERGENiHBG054379.
InParanoidiQ687X5.
KOiK19876.
OMAiYCVIREV.
OrthoDBiEOG091G0F9X.
PhylomeDBiQ687X5.
TreeFamiTF332031.

Family and domain databases

InterProiView protein in InterPro
IPR013130. Fe3_Rdtase_TM_dom.
IPR036291. NAD(P)-bd_dom_sf.
IPR028939. P5C_Rdtase_cat_N.
PfamiView protein in Pfam
PF03807. F420_oxidored. 1 hit.
PF01794. Ferric_reduct. 1 hit.
SUPFAMiSSF51735. SSF51735. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q687X5-1) [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
MEKTCIDALP LTMNSSEKQE TVCIFGTGDF GRSLGLKMLQ CGYSVVFGSR
60 70 80 90 100
NPQKTTLLPS GAEVLSYSEA AKKSGIIIIA IHREHYDFLT ELTEVLNGKI
110 120 130 140 150
LVDISNNLKI NQYPESNAEY LAHLVPGAHV VKAFNTISAW ALQSGALDAS
160 170 180 190 200
RQVFVCGNDS KAKQRVMDIV RNLGLTPMDQ GSLMAAKEIE KYPLQLFPMW
210 220 230 240 250
RFPFYLSAVL CVFLFFYCVI RDVIYPYVYE KKDNTFRMAI SIPNRIFPIT
260 270 280 290 300
ALTLLALVYL PGVIAAILQL YRGTKYRRFP DWLDHWMLCR KQLGLVALGF
310 320 330 340 350
AFLHVLYTLV IPIRYYVRWR LGNLTVTQAI LKKENPFSTS SAWLSDSYVA
360 370 380 390 400
LGILGFFLFV LLGITSLPSV SNAVNWREFR FVQSKLGYLT LILCTAHTLV
410 420 430 440 450
YGGKRFLSPS NLRWYLPAAY VLGLIIPCTV LVIKFVLIMP CVDNTLTRIR

QGWERNSKH
Length:459
Mass (Da):51,981
Last modified:October 11, 2004 - v1
Checksum:iFA3BF0F2B1001FE5
GO
Isoform 2 (identifier: Q687X5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     153-328: Missing.

Show »
Length:283
Mass (Da):31,310
Checksum:i05110EAC5D032317
GO

Sequence cautioni

The sequence AAQ04064 differs from that shown. Reason: Frameshift at position 384.Curated
The sequence BAB15559 differs from that shown. Reason: Frameshift at positions 252 and 364.Curated
The sequence CAH56271 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03197675G → D1 PublicationCorresponds to variant dbSNP:rs1981529Ensembl.1
Natural variantiVAR_031977122A → T. Corresponds to variant dbSNP:rs34741656Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_024833153 – 328Missing in isoform 2. 1 PublicationAdd BLAST176

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF423422 mRNA. Translation: AAQ04063.1.
AF423423 mRNA. Translation: AAQ04064.1. Frameshift.
AK026806 mRNA. Translation: BAB15559.1. Frameshift.
BC020600 mRNA. Translation: AAH20600.1.
AL833044 mRNA. Translation: CAH56271.1. Different initiation.
CCDSiCCDS43611.1. [Q687X5-1]
CCDS56494.1. [Q687X5-2]
RefSeqiNP_001192244.1. NM_001205315.1. [Q687X5-1]
NP_001192245.1. NM_001205316.1. [Q687X5-2]
NP_078912.2. NM_024636.3. [Q687X5-1]
UniGeneiHs.521008.

Genome annotation databases

EnsembliENST00000301959; ENSP00000305545; ENSG00000127954. [Q687X5-2]
ENST00000380079; ENSP00000369419; ENSG00000127954. [Q687X5-1]
GeneIDi79689.
KEGGihsa:79689.
UCSCiuc003ujs.4. human. [Q687X5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSTEA4_HUMAN
AccessioniPrimary (citable) accession number: Q687X5
Secondary accession number(s): Q658Q9
, Q687X4, Q8WWB0, Q9H5R1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: October 11, 2004
Last modified: October 25, 2017
This is version 114 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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. SIMILARITY comments
    Index of protein domains and families