UniProtKB - Q687X5 (STEA4_HUMAN)
Protein
Metalloreductase STEAP4
Gene
STEAP4
Organism
Homo sapiens (Human)
Status
Functioni
Integral membrane protein that functions as NADPH-dependent ferric-chelate reductase, using NADPH from one side of the membrane to reduce a Fe3+ chelate that is bound on the other side of the membrane. Mediates sequential transmembrane electron transfer from NADPH to FAD and onto heme, and finally to the Fe3+ chelate (PubMed:30337524). Can also reduce Cu2+ to Cu1+ (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 similarity5 Publications
Catalytic activityi
- EC:1.16.1.91 Publication
Cofactori
Protein has several cofactor binding sites:- FAD1 PublicationNote: Can also utilize FMN (PubMed:30337524). Can also utilize riboflavin.By similarity1 Publication
- heme1 Publication
Kineticsi
- KM=13.7 µM for Fe3+-NTA1 Publication
- KM=4.2 µM for NADPH1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 67 | NADPCombined sources1 Publication | 1 | |
Binding sitei | 106 | NADP; via amide nitrogenCombined sources1 Publication | 1 | |
Binding sitei | 139 | NADP; via amide nitrogenBy similarity | 1 | |
Binding sitei | 140 | FADCombined sources1 Publication | 1 | |
Binding sitei | 148 | FADCombined sources1 Publication | 1 | |
Binding sitei | 171 | NADPBy similarity | 1 | |
Binding sitei | 269 | FADCombined sources1 Publication | 1 | |
Binding sitei | 290 | FADCombined sources1 Publication | 1 | |
Metal bindingi | 304 | Iron (heme axial ligand)Combined sources1 Publication | 1 | |
Binding sitei | 366 | FADCombined sources1 Publication | 1 | |
Binding sitei | 383 | FADCombined sources1 Publication | 1 | |
Metal bindingi | 397 | Iron (heme axial ligand)Combined sources1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 27 – 30 | NADPCombined sources1 Publication | 4 | |
Nucleotide bindingi | 49 – 50 | NADPCombined sources1 Publication | 2 | |
Nucleotide bindingi | 81 – 85 | NADPCombined sources1 Publication | 5 |
GO - Molecular functioni
- cupric reductase activity Source: GO_Central
- electron transfer activity Source: UniProtKB
- FAD binding Source: UniProtKB
- ferric-chelate reductase (NADPH) activity Source: UniProtKB
- heme binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- copper ion import Source: GO_Central
- fat cell differentiation Source: UniProtKB
- iron ion homeostasis Source: UniProtKB-KW
- oxidation-reduction process Source: GO_Central
- protein homotrimerization Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase |
Biological process | Electron transport, Ion transport, Iron transport, Transport |
Ligand | Copper, FAD, Flavoprotein, Heme, Iron, Metal-binding, NADP |
Enzyme and pathway databases
PathwayCommonsi | Q687X5 |
Protein family/group databases
TCDBi | 5.B.6.1.3, the transmembrane epithelial antigen protein-3 ferric reductase (steap) family |
Names & Taxonomyi
Protein namesi | Recommended name: Metalloreductase STEAP4 (EC:1.16.1.91 Publication)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:STAMP21 Publication, TNFAIP9 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000127954.12 |
HGNCi | HGNC:21923, STEAP4 |
MIMi | 611098, gene |
neXtProti | NX_Q687X5 |
Subcellular locationi
Golgi apparatus
- Golgi apparatus membrane 1 Publication; Multi-pass membrane protein 1 Publication
Endosome
- Early endosome membrane 1 Publication; Multi-pass membrane protein 1 Publication
Plasma membrane
- Cell membrane 2 Publications; Multi-pass membrane protein 1 Publication
Endosome
- early endosome membrane Source: UniProtKB-SubCell
- endosome Source: GO_Central
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Golgi apparatus
- Golgi membrane Source: UniProtKB-SubCell
Nucleus
- nucleoplasm Source: HPA
Plasma Membrane
- plasma membrane Source: HPA
Other locations
- integral component of membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 202 – 224 | Helical1 PublicationAdd BLAST | 23 | |
Transmembranei | 236 – 256 | Helical1 PublicationAdd BLAST | 21 | |
Transmembranei | 293 – 313 | Helical1 PublicationAdd BLAST | 21 | |
Transmembranei | 342 – 362 | Helical1 PublicationAdd BLAST | 21 | |
Transmembranei | 381 – 401 | Helical1 PublicationAdd BLAST | 21 | |
Transmembranei | 419 – 439 | Helical1 PublicationAdd BLAST | 21 |
Keywords - Cellular componenti
Cell membrane, Endosome, Golgi apparatus, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 138 | S → Q: Strongly reduced enzyme activity. No effect on trimerization and on heme binding. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 79689 |
OpenTargetsi | ENSG00000127954 |
PharmGKBi | PA134874572 |
Miscellaneous databases
Pharosi | Q687X5, Tbio |
Polymorphism and mutation databases
BioMutai | STEAP4 |
DMDMi | 74748242 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000285174 | 1 – 459 | Metalloreductase STEAP4Add BLAST | 459 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 323 | N-linked (GlcNAc...) asparagineCombined sources2 Publications | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
EPDi | Q687X5 |
jPOSTi | Q687X5 |
MassIVEi | Q687X5 |
MaxQBi | Q687X5 |
PaxDbi | Q687X5 |
PeptideAtlasi | Q687X5 |
PRIDEi | Q687X5 |
ProteomicsDBi | 65993 [Q687X5-1] 65994 [Q687X5-2] |
PTM databases
GlyGeni | Q687X5, 1 site |
iPTMneti | Q687X5 |
PhosphoSitePlusi | Q687X5 |
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
Bgeei | ENSG00000127954, Expressed in pericardium and 197 other tissues |
ExpressionAtlasi | Q687X5, baseline and differential |
Genevisiblei | Q687X5, HS |
Organism-specific databases
HPAi | ENSG00000127954, Tissue enhanced (adipose) |
Interactioni
Subunit structurei
Homotrimer (PubMed:30337524).
Interacts with PTK2/FAK1; the interaction may regulate PTK2 phosphorylation.
2 PublicationsProtein-protein interaction databases
BioGRIDi | 122810, 2 interactors |
IntActi | Q687X5, 2 interactors |
STRINGi | 9606.ENSP00000369419 |
Miscellaneous databases
RNActi | Q687X5, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q687X5 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 247 – 395 | Ferric oxidoreductaseSequence analysisAdd BLAST | 149 |
Sequence similaritiesi
Belongs to the STEAP family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502R746, Eukaryota |
GeneTreei | ENSGT00390000008042 |
HOGENOMi | CLU_034618_1_1_1 |
InParanoidi | Q687X5 |
OMAi | CTFHTYL |
OrthoDBi | 638341at2759 |
PhylomeDBi | Q687X5 |
TreeFami | TF332031 |
Family and domain databases
InterProi | View protein in InterPro IPR013130, Fe3_Rdtase_TM_dom IPR036291, NAD(P)-bd_dom_sf IPR028939, P5C_Rdtase_cat_N |
Pfami | View protein in Pfam PF03807, F420_oxidored, 1 hit PF01794, Ferric_reduct, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q687X5-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketC9JS50 | C9JS50_HUMAN | Metalloreductase STEAP4 | STEAP4 | 339 | Annotation score: |
Sequence cautioni
The sequence AAQ04064 differs from that shown. Reason: Frameshift.Curated
The sequence BAB15559 differs from that shown. Reason: Frameshift.Curated
The sequence CAH56271 differs from that shown. Reason: Erroneous initiation.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_031976 | 75 | G → D1 PublicationCorresponds to variant dbSNP:rs1981529Ensembl. | 1 | |
Natural variantiVAR_031977 | 122 | A → T. Corresponds to variant dbSNP:rs34741656Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_024833 | 153 – 328 | Missing in isoform 2. 1 PublicationAdd BLAST | 176 |
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. |
CCDSi | CCDS43611.1 [Q687X5-1] CCDS56494.1 [Q687X5-2] |
RefSeqi | NP_001192244.1, NM_001205315.1 [Q687X5-1] NP_001192245.1, NM_001205316.1 [Q687X5-2] NP_078912.2, NM_024636.3 [Q687X5-1] |
Genome annotation databases
Ensembli | ENST00000301959; ENSP00000305545; ENSG00000127954 [Q687X5-2] ENST00000380079; ENSP00000369419; ENSG00000127954 [Q687X5-1] |
GeneIDi | 79689 |
KEGGi | hsa:79689 |
UCSCi | uc003ujs.4, human [Q687X5-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
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. |
CCDSi | CCDS43611.1 [Q687X5-1] CCDS56494.1 [Q687X5-2] |
RefSeqi | NP_001192244.1, NM_001205315.1 [Q687X5-1] NP_001192245.1, NM_001205316.1 [Q687X5-2] NP_078912.2, NM_024636.3 [Q687X5-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6HCY | electron microscopy | 3.10 | A/B/C | 1-459 | [»] | |
6HD1 | electron microscopy | 3.80 | A/B/C | 1-459 | [»] | |
SMRi | Q687X5 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 122810, 2 interactors |
IntActi | Q687X5, 2 interactors |
STRINGi | 9606.ENSP00000369419 |
Protein family/group databases
TCDBi | 5.B.6.1.3, the transmembrane epithelial antigen protein-3 ferric reductase (steap) family |
PTM databases
GlyGeni | Q687X5, 1 site |
iPTMneti | Q687X5 |
PhosphoSitePlusi | Q687X5 |
Polymorphism and mutation databases
BioMutai | STEAP4 |
DMDMi | 74748242 |
Proteomic databases
EPDi | Q687X5 |
jPOSTi | Q687X5 |
MassIVEi | Q687X5 |
MaxQBi | Q687X5 |
PaxDbi | Q687X5 |
PeptideAtlasi | Q687X5 |
PRIDEi | Q687X5 |
ProteomicsDBi | 65993 [Q687X5-1] 65994 [Q687X5-2] |
Protocols and materials databases
Antibodypediai | 29814, 281 antibodies |
Genome annotation databases
Ensembli | ENST00000301959; ENSP00000305545; ENSG00000127954 [Q687X5-2] ENST00000380079; ENSP00000369419; ENSG00000127954 [Q687X5-1] |
GeneIDi | 79689 |
KEGGi | hsa:79689 |
UCSCi | uc003ujs.4, human [Q687X5-1] |
Organism-specific databases
CTDi | 79689 |
DisGeNETi | 79689 |
EuPathDBi | HostDB:ENSG00000127954.12 |
GeneCardsi | STEAP4 |
HGNCi | HGNC:21923, STEAP4 |
HPAi | ENSG00000127954, Tissue enhanced (adipose) |
MIMi | 611098, gene |
neXtProti | NX_Q687X5 |
OpenTargetsi | ENSG00000127954 |
PharmGKBi | PA134874572 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502R746, Eukaryota |
GeneTreei | ENSGT00390000008042 |
HOGENOMi | CLU_034618_1_1_1 |
InParanoidi | Q687X5 |
OMAi | CTFHTYL |
OrthoDBi | 638341at2759 |
PhylomeDBi | Q687X5 |
TreeFami | TF332031 |
Enzyme and pathway databases
PathwayCommonsi | Q687X5 |
Miscellaneous databases
BioGRID-ORCSi | 79689, 4 hits in 840 CRISPR screens |
ChiTaRSi | STEAP4, human |
GenomeRNAii | 79689 |
Pharosi | Q687X5, Tbio |
PROi | PR:Q687X5 |
RNActi | Q687X5, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000127954, Expressed in pericardium and 197 other tissues |
ExpressionAtlasi | Q687X5, baseline and differential |
Genevisiblei | Q687X5, HS |
Family and domain databases
InterProi | View protein in InterPro IPR013130, Fe3_Rdtase_TM_dom IPR036291, NAD(P)-bd_dom_sf IPR028939, P5C_Rdtase_cat_N |
Pfami | View protein in Pfam PF03807, F420_oxidored, 1 hit PF01794, Ferric_reduct, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | STEA4_HUMAN | |
Accessioni | Q687X5Primary (citable) accession number: Q687X5 Secondary accession number(s): Q658Q9 Q9H5R1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 1, 2007 |
Last sequence update: | October 11, 2004 | |
Last modified: | December 2, 2020 | |
This is version 134 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations