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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+. Uses NAD+ as acceptor. Plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses (By similarity). Associated with obesity and insulin-resistance. Involved in inflammatory arthritis, through the regulation of inflammatory cytokines. Inhibits anchorage-independent cell proliferation.By similarity4 Publications

Cofactori

FADBy similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi304 – 3041Iron (heme axial ligand)By similarity
Metal bindingi397 – 3971Iron (heme axial ligand)By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Ion transport, Iron transport, Transport

Keywords - Ligandi

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

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

HGNCiHGNC:21923. STEAP4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei196 – 21621HelicalSequence analysisAdd
BLAST
Transmembranei246 – 26621HelicalSequence analysisAdd
BLAST
Transmembranei293 – 31321HelicalSequence analysisAdd
BLAST
Transmembranei348 – 36821HelicalSequence analysisAdd
BLAST
Transmembranei381 – 40121HelicalSequence analysisAdd
BLAST
Transmembranei419 – 43921HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

  • endosome Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • Golgi membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134874572.

Polymorphism and mutation databases

BioMutaiSTEAP4.
DMDMi74748242.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 459459Metalloreductase STEAP4PRO_0000285174Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi323 – 3231N-linked (GlcNAc...)1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ687X5.
MaxQBiQ687X5.
PaxDbiQ687X5.
PRIDEiQ687X5.

PTM databases

PhosphoSiteiQ687X5.

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

BgeeiQ687X5.
CleanExiHS_STEAP4.
ExpressionAtlasiQ687X5. baseline and differential.
GenevisibleiQ687X5. HS.

Interactioni

Subunit structurei

Interacts with and phosphorylates PTK2/FAK1.1 Publication

Protein-protein interaction databases

BioGridi122810. 2 interactions.
IntActiQ687X5. 1 interaction.
STRINGi9606.ENSP00000369419.

Structurei

3D structure databases

ProteinModelPortaliQ687X5.
SMRiQ687X5. Positions 19-195.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini247 – 395149Ferric oxidoreductaseAdd
BLAST

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.
HOGENOMiHOG000234491.
HOVERGENiHBG054379.
InParanoidiQ687X5.
KOiK19876.
OMAiYCVIREV.
OrthoDBiEOG7Z0JWH.
PhylomeDBiQ687X5.
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 (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 AAQ04064.1 differs from that shown. Reason: Frameshift at position 384. Curated
The sequence BAB15559.1 differs from that shown. Reason: Frameshift at positions 252 and 364. Curated
The sequence CAH56271.1 differs from that shown. Reason: Erroneous initiation. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti75 – 751G → D.1 Publication
Corresponds to variant rs1981529 [ dbSNP | Ensembl ].
VAR_031976
Natural varianti122 – 1221A → T.
Corresponds to variant rs34741656 [ dbSNP | Ensembl ].
VAR_031977

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei153 – 328176Missing in isoform 2. 1 PublicationVSP_024833Add
BLAST

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

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.
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.

3D structure databases

ProteinModelPortaliQ687X5.
SMRiQ687X5. Positions 19-195.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122810. 2 interactions.
IntActiQ687X5. 1 interaction.
STRINGi9606.ENSP00000369419.

Protein family/group databases

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

PTM databases

PhosphoSiteiQ687X5.

Polymorphism and mutation databases

BioMutaiSTEAP4.
DMDMi74748242.

Proteomic databases

EPDiQ687X5.
MaxQBiQ687X5.
PaxDbiQ687X5.
PRIDEiQ687X5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi79689.
GeneCardsiSTEAP4.
HGNCiHGNC:21923. STEAP4.
MIMi611098. gene.
neXtProtiNX_Q687X5.
PharmGKBiPA134874572.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF4F. Eukaryota.
COG2085. LUCA.
GeneTreeiENSGT00390000008042.
HOGENOMiHOG000234491.
HOVERGENiHBG054379.
InParanoidiQ687X5.
KOiK19876.
OMAiYCVIREV.
OrthoDBiEOG7Z0JWH.
PhylomeDBiQ687X5.
TreeFamiTF332031.

Miscellaneous databases

ChiTaRSiSTEAP4. human.
GenomeRNAii79689.
NextBioi68956.
PROiQ687X5.
SOURCEiSearch...

Gene expression databases

BgeeiQ687X5.
CleanExiHS_STEAP4.
ExpressionAtlasiQ687X5. baseline and differential.
GenevisibleiQ687X5. 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...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and characterization of STAMP2, an androgen-regulated six transmembrane protein that is overexpressed in prostate cancer."
    Korkmaz C.G., Korkmaz K.S., Kurys P., Elbi C., Wang L., Klokk T.I., Hammarstrom C., Troen G., Svindland A., Hager G.L., Saatcioglu F.
    Oncogene 24:4934-4945(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
    Tissue: Prostatic carcinoma.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASP-75.
    Tissue: Lung.
  3. "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 2).
    Tissue: Lung.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 325-459.
    Tissue: Stomach.
  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: TISSUE SPECIFICITY.
  6. "Downregulation of STEAP4, a highly-expressed TNF-alpha-inducible gene in adipose tissue, is associated with obesity in humans."
    Zhang C.M., Chi X., Wang B., Zhang M., Ni Y.H., Chen R.H., Li X.N., Guo X.R.
    Acta Pharmacol. Sin. 29:587-592(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION BY TNF.
  7. "Expression of six transmembrane protein of prostate 2 in human adipose tissue associates with adiposity and insulin resistance."
    Arner P., Stenson B.M., Dungner E., Naeslund E., Hoffstedt J., Ryden M., Dahlman I.
    J. Clin. Endocrinol. Metab. 93:2249-2254(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  8. "Tumor necrosis factor alpha-induced adipose-related protein expression in experimental arthritis and in rheumatoid arthritis."
    Inoue A., Matsumoto I., Tanaka Y., Iwanami K., Kanamori A., Ochiai N., Goto D., Ito S., Sumida T.
    Arthritis Res. Ther. 11:R118-R118(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  9. "Interleukin-1beta is a positive regulator of TIARP/STAMP2 gene and protein expression in adipocytes in vitro."
    Kralisch S., Sommer G., Weise S., Lipfert J., Lossner U., Kamprad M., Schrock K., Bluher M., Stumvoll M., Fasshauer M.
    FEBS Lett. 583:1196-1200(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY IL1B, TISSUE SPECIFICITY.
  10. "STEAP4 regulates focal adhesion kinase activation and CpG motifs within STEAP4 promoter region are frequently methylated in DU145, human androgen-independent prostate cancer cells."
    Tamura T., Chiba J.
    Int. J. Mol. Med. 24:599-604(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PTK2/FAK1, SUBCELLULAR LOCATION.
  11. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-323.
    Tissue: Liver.

Entry informationi

Entry nameiSTEA4_HUMAN
AccessioniPrimary (citable) accession number: Q687X5
Secondary accession number(s): Q658Q9
, Q687X4, Q8WWB0, Q9H5R1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: October 11, 2004
Last modified: May 11, 2016
This is version 101 of the entry and version 1 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

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

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.