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Protein

Metalloreductase STEAP4

Gene

Steap4

Organism
Mus musculus (Mouse)
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. Inhibits anchorage-independent cell proliferation (By similarity). Associated with obesity and insulin-resistance. Involved in inflammatory arthritis, through the regulation of inflammatory cytokines. Plays a role in systemic metabolic homeostasis, integrating inflammatory and metabolic responses.By similarity3 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

  • cupric reductase activity Source: MGI
  • ferric-chelate reductase (NADPH) activity Source: MGI
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

  • copper ion import Source: MGI
  • fat cell differentiation Source: UniProtKB
  • ferric iron import into cell Source: MGI
  • iron ion homeostasis Source: UniProtKB-KW
  • oxidation-reduction process Source: MGI
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

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloreductase STEAP4 (EC:1.16.1.-)
Alternative name(s):
Dudulin-4
Six-transmembrane epithelial antigen of prostate 4
Tumor necrosis factor-alpha-induced adipose-related protein
Gene namesi
Name:Steap4
Synonyms:Tiarp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1923560. Steap4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei196 – 21621HelicalSequence analysisAdd
BLAST
Transmembranei247 – 26721HelicalSequence analysisAdd
BLAST
Transmembranei293 – 31321HelicalSequence analysisAdd
BLAST
Transmembranei348 – 36821HelicalSequence analysisAdd
BLAST
Transmembranei386 – 40217HelicalSequence analysisAdd
BLAST
Transmembranei419 – 43921HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice are viable and fertile, but exhibit overt inflammation with increased expression of Il6, Tnfa, Ccl2, haptoglobin and Socs3 in visceral adipose tissue as well as macrophage infiltration. They develop metabolic disease on regular diet with insulin resistance, glucose intolerance, mild hyperglycemia, dyslipidemia, and fatty liver disease. Adipocytes isolated from visceral fat exhibit severily defective glucose transport, with decreased expression of Slc2a4, Adipoq, Fas and Pparg. Glucose disposal is lower in response to insulin stimulation and hepatic glucose production is higher, confirming systemic and hepatic insulin-resistance.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 470470Metalloreductase STEAP4PRO_0000285175Add
BLAST

Proteomic databases

MaxQBiQ923B6.
PaxDbiQ923B6.
PRIDEiQ923B6.

PTM databases

iPTMnetiQ923B6.
PhosphoSiteiQ923B6.

Expressioni

Tissue specificityi

Expressed in white and brown adipose tissues cells, as well as in muscle and liver cells. Detected in joints and spleens of arthritic mice.2 Publications

Inductioni

By Tnfa (TNF-alpha), by Il6 in white and brown adipose tissue, and IL1B in white adipose tissue. Tnfa, Il6 and Il1b shows sinergistic stimulatory effects.5 Publications

Gene expression databases

BgeeiQ923B6.
CleanExiMM_STEAP4.
GenevisibleiQ923B6. MM.

Interactioni

Subunit structurei

Interacts with and phosphorylates PTK2/FAK1.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000111081.

Structurei

3D structure databases

ProteinModelPortaliQ923B6.
SMRiQ923B6. 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.
InParanoidiQ923B6.
KOiK19876.
OMAiYCVIREV.
OrthoDBiEOG7Z0JWH.
PhylomeDBiQ923B6.
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.

Sequencei

Sequence statusi: Complete.

Q923B6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKAHADEFP LTTDSSEKQG VVCIFGTGDF GKSLGLKMLQ CGYSIVFGSR
60 70 80 90 100
NPQVSSLLPR GAEVLSYSEA ASKSDIIILA MHREHYDSLT ELVDYLKGKV
110 120 130 140 150
LVDVSNNRKI NQYPESNAEY LAQLEPGAHV VKAFNTISAW ALQSGTLDAS
160 170 180 190 200
RQVFVCGNDS KAKQRVMDIA RTLGLTPLDQ GSLMAASEIE NYPLQLFPMW
210 220 230 240 250
RFPFYLSSVL CVFFFVYCAI REVIYPYVNG KTDATYRLAI SIPNRVFPIT
260 270 280 290 300
ALILLALVYL PGILAAILQL YRGTKYRRFP NWLDHWMLCR KQLGLVALGF
310 320 330 340 350
AFLHVIYTLV IPIRYYVRWR LRNATITQAL TNKDSPFITS YAWINDSYLA
360 370 380 390 400
LGILGFFLFL LLGITSLPSV SNMVNWREFR FVQSKLGYLT LVLCTAHTLV
410 420 430 440 450
YGGKRFLSPS ILRWSLPSAY ILALVIPCAV LVLKCILIMP CIDKTLTRIR
460 470
QGWERNSKYT QSALNGKSDI
Length:470
Mass (Da):52,994
Last modified:December 1, 2001 - v1
Checksum:i6823E7682AC78B19
GO

Sequence cautioni

The sequence AAK40270.1 differs from that shown. Reason: Frameshift at positions 334, 336 and 453. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti36 – 361L → M in AAK40270 (Ref. 2) Curated
Sequence conflicti95 – 951Y → C in CAC41351 (PubMed:11443137).Curated
Sequence conflicti108 – 1081R → H in AAK40270 (Ref. 2) Curated
Sequence conflicti127 – 1271G → E in AAK40270 (Ref. 2) Curated
Sequence conflicti154 – 1541F → L in AAK40270 (Ref. 2) Curated
Sequence conflicti164 – 1641Q → H in CAC41351 (PubMed:11443137).Curated
Sequence conflicti212 – 2121V → I in CAC41351 (PubMed:11443137).Curated
Sequence conflicti212 – 2121V → I in AAK40270 (Ref. 2) Curated
Sequence conflicti216 – 2161V → L in AAK40270 (Ref. 2) Curated
Sequence conflicti228 – 2281V → M in AAK40270 (Ref. 2) Curated
Sequence conflicti305 – 3051V → A in AAK40270 (Ref. 2) Curated
Sequence conflicti323 – 3231N → K in AAK40270 (Ref. 2) Curated
Sequence conflicti332 – 3321N → S in AAK40270 (Ref. 2) Curated
Sequence conflicti362 – 3621L → V in AAK40270 (Ref. 2) Curated
Sequence conflicti425 – 4251V → I in CAC41351 (PubMed:11443137).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ319746 mRNA. Translation: CAC41351.1.
AY029778 mRNA. Translation: AAK40270.1. Frameshift.
AK040760 mRNA. Translation: BAC30696.1.
BC006651 mRNA. Translation: AAH06651.1.
CCDSiCCDS39008.1.
RefSeqiNP_473439.2. NM_054098.3.
UniGeneiMm.31403.

Genome annotation databases

EnsembliENSMUST00000115421; ENSMUSP00000111081; ENSMUSG00000012428.
GeneIDi117167.
KEGGimmu:117167.
UCSCiuc008wjg.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ319746 mRNA. Translation: CAC41351.1.
AY029778 mRNA. Translation: AAK40270.1. Frameshift.
AK040760 mRNA. Translation: BAC30696.1.
BC006651 mRNA. Translation: AAH06651.1.
CCDSiCCDS39008.1.
RefSeqiNP_473439.2. NM_054098.3.
UniGeneiMm.31403.

3D structure databases

ProteinModelPortaliQ923B6.
SMRiQ923B6. Positions 19-195.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000111081.

PTM databases

iPTMnetiQ923B6.
PhosphoSiteiQ923B6.

Proteomic databases

MaxQBiQ923B6.
PaxDbiQ923B6.
PRIDEiQ923B6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000115421; ENSMUSP00000111081; ENSMUSG00000012428.
GeneIDi117167.
KEGGimmu:117167.
UCSCiuc008wjg.1. mouse.

Organism-specific databases

CTDi79689.
MGIiMGI:1923560. Steap4.

Phylogenomic databases

eggNOGiENOG410IF4F. Eukaryota.
COG2085. LUCA.
GeneTreeiENSGT00390000008042.
HOGENOMiHOG000234491.
HOVERGENiHBG054379.
InParanoidiQ923B6.
KOiK19876.
OMAiYCVIREV.
OrthoDBiEOG7Z0JWH.
PhylomeDBiQ923B6.
TreeFamiTF332031.

Miscellaneous databases

PROiQ923B6.
SOURCEiSearch...

Gene expression databases

BgeeiQ923B6.
CleanExiMM_STEAP4.
GenevisibleiQ923B6. MM.

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. "Tumor necrosis factor-alpha-induced adipose-related protein (TIARP), a cell-surface protein that is highly induced by tumor necrosis factor-alpha and adipose conversion."
    Moldes M., Lasnier F., Gauthereau X., Klein C., Pairault J., Feve B., Chambaut-Guerin A.-M.
    J. Biol. Chem. 276:33938-33946(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION BY TNFA.
    Strain: SWR/J.
    Tissue: Adipose tissue.
  2. "Molecular cloning and expression of two new members of the dudulin family."
    Serru V., Lamblin D., Manivet P., Pernet P., Vaubourdolle M., Kellermann O., Loric S.
    Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  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.
    , 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].
    Strain: C57BL/6J.
    Tissue: Aorta and Vein.
  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].
    Strain: FVB/N.
    Tissue: Mammary tumor.
  5. "Interleukin-6 is a positive regulator of tumor necrosis factor alpha-induced adipose-related protein in 3T3-L1 adipocytes."
    Fasshauer M., Kralisch S., Klier M., Lossner U., Bluher M., Chambaut-Guerin A.-M., Klein J., Paschke R.
    FEBS Lett. 560:153-157(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY IL6, TISSUE SPECIFICITY.
  6. Cited for: FUNCTION, ENZYME ACTIVITY.
  7. "Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis."
    Wellen K.E., Fucho R., Gregor M.F., Furuhashi M., Morgan C., Lindstad T., Vaillancourt E., Gorgun C.Z., Saatcioglu F., Hotamisligil G.S.
    Cell 129:537-548(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION BY TNFA, DISRUPTION PHENOTYPE.
  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, INDUCTION BY TNFA, 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.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brown adipose tissue, Heart and Liver.

Entry informationi

Entry nameiSTEA4_MOUSE
AccessioniPrimary (citable) accession number: Q923B6
Secondary accession number(s): Q91W31, Q91ZE8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: December 1, 2001
Last modified: June 8, 2016
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.