STEA3_HUMAN
ID STEA3_HUMAN Reviewed; 488 AA.
AC Q658P3; A8K6E3; Q4VBR2; Q4ZG36; Q53SQ8; Q7Z389; Q86SF6; Q8NEW6; Q8TDP3;
AC Q8TF03; Q9NVB5;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Metalloreductase STEAP3;
DE EC=1.16.1.-;
DE AltName: Full=Dudulin-2;
DE AltName: Full=Six-transmembrane epithelial antigen of prostate 3;
DE AltName: Full=Tumor suppressor-activated pathway protein 6;
DE Short=hTSAP6;
DE AltName: Full=pHyde;
DE Short=hpHyde;
GN Name=STEAP3; Synonyms=TSAP6;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INDUCTION, AND
RP INTERACTION WITH BNIP3L AND MYT1.
RX PubMed=12606722; DOI=10.1073/pnas.0530298100;
RA Passer B.J., Nancy-Portebois V., Amzallag N., Prieur S., Cans C.,
RA Roborel de Climens A., Fiucci G., Bouvard V., Tuynder M., Susini L.,
RA Morchoisne S., Crible V., Lespagnol A., Dausset J., Oren M., Amson R.,
RA Telerman A.;
RT "The p53-inducible TSAP6 gene product regulates apoptosis and the cell
RT cycle and interacts with Nix and the Myt1 kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2284-2289(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=15897894; DOI=10.1038/sj.onc.1208677;
RA Korkmaz C.G., Korkmaz K.S., Kurys P., Elbi C., Wang L., Klokk T.I.,
RA Hammarstrom C., Troen G., Svindland A., Hager G.L., Saatcioglu F.;
RT "Molecular cloning and characterization of STAMP2, an androgen-regulated
RT six transmembrane protein that is overexpressed in prostate cancer.";
RL Oncogene 24:4934-4945(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RX PubMed=10969787;
RA Steiner M.S., Zhang X., Wang Y., Lu Y.;
RT "Growth inhibition of prostate cancer by an adenovirus expressing a novel
RT tumor suppressor gene, pHyde.";
RL Cancer Res. 60:4419-4425(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Serru V., Manivet P., Lenoir C., Eschwege P., Lamblin D., Vaubourdolle M.,
RA Kellermann O., Loric S.;
RT "Dudulin 2, a new tumor antigen expressed in various human tumors.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Lu Y., Beheshti B., Squire J.A., Yang X.J.;
RT "Characterization of a novel apoptosis-inducing gene, hpHyde, that inhibits
RT prostate cancer cell growth.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon endothelium, and Endometrial adenocarcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP LACK OF TUMOR SUPPRESSOR FUNCTION.
RX PubMed=12866033; DOI=10.1002/ijc.11278;
RA Porkka K.P., Nupponen N.N., Tammela T.L., Vessella R.L., Visakorpi T.;
RT "Human pHyde is not a classical tumor suppressor gene in prostate cancer.";
RL Int. J. Cancer 106:729-735(2003).
RN [12]
RP FUNCTION, AND INTERACTION WITH TCTP.
RX PubMed=15319436; DOI=10.1074/jbc.m404850200;
RA Amzallag N., Passer B.J., Allanic D., Segura E., Thery C., Goud B.,
RA Amson R., Telerman A.;
RT "TSAP6 facilitates the secretion of translationally controlled tumor
RT protein/histamine-releasing factor via a nonclassical pathway.";
RL J. Biol. Chem. 279:46104-46112(2004).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=15885357; DOI=10.1016/j.jhep.2005.01.027;
RA Coulouarn C., Derambure C., Lefebvre G., Daveau R., Hiron M., Scotte M.,
RA Francois A., Daveau M., Salier J.-P.;
RT "Global gene repression in hepatocellular carcinoma and fetal liver, and
RT suppression of dudulin-2 mRNA as a possible marker for the cirrhosis-to-
RT tumor transition.";
RL J. Hepatol. 42:860-869(2005).
RN [14]
RP TISSUE SPECIFICITY.
RX PubMed=16227996; DOI=10.1038/ng1658;
RA Ohgami R.S., Campagna D.R., Greer E.L., Antiochos B., McDonald A., Chen J.,
RA Sharp J.J., Fujiwara Y., Barker J.E., Fleming M.D.;
RT "Identification of a ferrireductase required for efficient transferrin-
RT dependent iron uptake in erythroid cells.";
RL Nat. Genet. 37:1264-1269(2005).
RN [15]
RP FUNCTION.
RX PubMed=16651434; DOI=10.1158/0008-5472.can-05-4579;
RA Yu X., Harris S.L., Levine A.J.;
RT "The regulation of exosome secretion: a novel function of the p53
RT protein.";
RL Cancer Res. 66:4795-4801(2006).
RN [16]
RP INVOLVEMENT IN AHMIO2.
RX PubMed=22031863; DOI=10.1182/blood-2011-01-329011;
RA Grandchamp B., Hetet G., Kannengiesser C., Oudin C., Beaumont C.,
RA Rodrigues-Ferreira S., Amson R., Telerman A., Nielsen P., Kohne E.,
RA Balser C., Heimpel H.;
RT "A novel type of congenital hypochromic anemia associated with a nonsense
RT mutation in the STEAP3/TSAP6 gene.";
RL Blood 118:6660-6666(2011).
RN [17]
RP CLEAVAGE BY RHBDD1, INTERACTION WITH RHBDD1, GLYCOSYLATION AT ASN-256 AND
RP ASN-344, AND MUTAGENESIS OF ASN-256; LEU-325 AND ASN-344.
RX PubMed=22624035; DOI=10.1371/journal.pone.0037452;
RA Wan C., Fu J., Wang Y., Miao S., Song W., Wang L.;
RT "Exosome-related multi-pass transmembrane protein TSAP6 is a target of
RT rhomboid protease RHBDD1-induced proteolysis.";
RL PLoS ONE 7:E37452-E37452(2012).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-17; SER-20 AND
RP THR-474, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-215 ALONE AND IN COMPLEX WITH
RP NADPH, AND SUBUNIT.
RX PubMed=18495927; DOI=10.1073/pnas.0801318105;
RA Sendamarai A.K., Ohgami R.S., Fleming M.D., Lawrence C.M.;
RT "Structure of the membrane proximal oxidoreductase domain of human Steap3,
RT the dominant ferrireductase of the erythroid transferrin cycle.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7410-7415(2008).
CC -!- FUNCTION: Endosomal ferrireductase required for efficient transferrin-
CC dependent iron uptake in erythroid cells. Participates in erythroid
CC iron homeostasis by reducing Fe(3+) to Fe(2+). Can also reduce of
CC Cu(2+) to Cu(1+), suggesting that it participates in copper
CC homeostasis. Uses NADP(+) as acceptor. May play a role downstream of
CC p53/TP53 to interface apoptosis and cell cycle progression. Indirectly
CC involved in exosome secretion by facilitating the secretion of proteins
CC such as TCTP. {ECO:0000269|PubMed:15319436,
CC ECO:0000269|PubMed:16651434}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q687X5};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q687X5};
CC -!- SUBUNIT: Homodimer. Interacts with BNIP3L, MYT1, RHBDL4/RHBDD1 and
CC TCTP. {ECO:0000269|PubMed:12606722, ECO:0000269|PubMed:15319436,
CC ECO:0000269|PubMed:18495927, ECO:0000269|PubMed:22624035}.
CC -!- INTERACTION:
CC Q658P3-1; Q658P3-1: STEAP3; NbExp=2; IntAct=EBI-15703397, EBI-15703397;
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250}; Multi-pass
CC membrane protein {ECO:0000250}. Note=Localizes to vesicular-like
CC structures at the plasma membrane and around the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q658P3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q658P3-2; Sequence=VSP_024829;
CC Name=3;
CC IsoId=Q658P3-3; Sequence=VSP_024830;
CC Name=4; Synonyms=pHyde II;
CC IsoId=Q658P3-4; Sequence=VSP_024830, VSP_024831;
CC -!- TISSUE SPECIFICITY: Expressed in adult bone marrow, placenta, liver,
CC skeletal muscle and pancreas. Down-regulated in hepatocellular
CC carcinoma. {ECO:0000269|PubMed:12606722, ECO:0000269|PubMed:15885357,
CC ECO:0000269|PubMed:16227996}.
CC -!- INDUCTION: By p53/TP53. {ECO:0000269|PubMed:12606722}.
CC -!- PTM: Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced
CC cleavage occurs at multiple sites in a glycosylation-independent
CC manner. {ECO:0000269|PubMed:22624035}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:22624035}.
CC -!- DISEASE: Anemia, hypochromic microcytic, with iron overload 2 (AHMIO2)
CC [MIM:615234]: A hematologic disease characterized by abnormal
CC hemoglobin content in the erythrocytes which are reduced in size,
CC severe anemia, erythropoietic hyperplasia of bone marrow, massive
CC hepatic iron deposition, and hepatosplenomegaly.
CC {ECO:0000269|PubMed:22031863}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the STEAP family. {ECO:0000305}.
CC -!- CAUTION: Was initially thought to have tumor suppressor function in
CC prostate cancer. However, it was shown that it is probably not the case
CC (PubMed:12866033). {ECO:0000305|PubMed:12866033}.
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DR EMBL; AY214461; AAO38238.1; -; mRNA.
DR EMBL; AF423424; AAQ04065.1; -; mRNA.
DR EMBL; AF238864; AAL78206.1; -; mRNA.
DR EMBL; AF262322; AAM08128.1; -; mRNA.
DR EMBL; AY029585; AAK50538.1; -; mRNA.
DR EMBL; AY082673; AAM45136.1; -; mRNA.
DR EMBL; AK001691; BAA91839.1; -; mRNA.
DR EMBL; AK291608; BAF84297.1; -; mRNA.
DR EMBL; AL833624; CAH56204.1; -; mRNA.
DR EMBL; BX538047; CAD97986.1; -; mRNA.
DR EMBL; AC016673; AAX88963.1; -; Genomic_DNA.
DR EMBL; AC016736; AAY14872.1; -; Genomic_DNA.
DR EMBL; CH471103; EAW95209.1; -; Genomic_DNA.
DR EMBL; BC042150; AAH42150.1; -; mRNA.
DR EMBL; BC095421; AAH95421.2; -; mRNA.
DR CCDS; CCDS2125.1; -. [Q658P3-1]
DR CCDS; CCDS42738.1; -. [Q658P3-2]
DR RefSeq; NP_001008410.1; NM_001008410.1. [Q658P3-1]
DR RefSeq; NP_060704.2; NM_018234.2. [Q658P3-1]
DR RefSeq; NP_619543.2; NM_138637.2.
DR RefSeq; NP_878919.2; NM_182915.2. [Q658P3-2]
DR RefSeq; XP_006712677.1; XM_006712614.3. [Q658P3-1]
DR RefSeq; XP_006712678.1; XM_006712615.1. [Q658P3-1]
DR RefSeq; XP_011509705.1; XM_011511403.1. [Q658P3-1]
DR PDB; 2VNS; X-ray; 2.00 A; A/B=1-215.
DR PDB; 2VQ3; X-ray; 2.00 A; A/B=1-215.
DR PDBsum; 2VNS; -.
DR PDBsum; 2VQ3; -.
DR AlphaFoldDB; Q658P3; -.
DR SMR; Q658P3; -.
DR BioGRID; 120533; 133.
DR IntAct; Q658P3; 37.
DR MINT; Q658P3; -.
DR STRING; 9606.ENSP00000376822; -.
DR TCDB; 5.B.6.1.1; the transmembrane epithelial antigen protein-3 ferric reductase (steap) family.
DR GlyGen; Q658P3; 2 sites.
DR iPTMnet; Q658P3; -.
DR PhosphoSitePlus; Q658P3; -.
DR SwissPalm; Q658P3; -.
DR BioMuta; STEAP3; -.
DR DMDM; 146325737; -.
DR EPD; Q658P3; -.
DR jPOST; Q658P3; -.
DR MassIVE; Q658P3; -.
DR MaxQB; Q658P3; -.
DR PaxDb; Q658P3; -.
DR PeptideAtlas; Q658P3; -.
DR PRIDE; Q658P3; -.
DR ProteomicsDB; 65924; -. [Q658P3-1]
DR ProteomicsDB; 65925; -. [Q658P3-2]
DR ProteomicsDB; 65926; -. [Q658P3-3]
DR ProteomicsDB; 65927; -. [Q658P3-4]
DR Antibodypedia; 18292; 296 antibodies from 34 providers.
DR DNASU; 55240; -.
DR Ensembl; ENST00000393106.6; ENSP00000376818.2; ENSG00000115107.20. [Q658P3-1]
DR Ensembl; ENST00000393107.2; ENSP00000376819.2; ENSG00000115107.20. [Q658P3-1]
DR Ensembl; ENST00000393110.7; ENSP00000376822.2; ENSG00000115107.20. [Q658P3-2]
DR GeneID; 55240; -.
DR KEGG; hsa:55240; -.
DR MANE-Select; ENST00000393110.7; ENSP00000376822.2; NM_182915.3; NP_878919.2. [Q658P3-2]
DR UCSC; uc002tlp.4; human. [Q658P3-1]
DR CTD; 55240; -.
DR DisGeNET; 55240; -.
DR GeneCards; STEAP3; -.
DR HGNC; HGNC:24592; STEAP3.
DR HPA; ENSG00000115107; Tissue enhanced (liver, parathyroid gland).
DR MalaCards; STEAP3; -.
DR MIM; 609671; gene.
DR MIM; 615234; phenotype.
DR neXtProt; NX_Q658P3; -.
DR OpenTargets; ENSG00000115107; -.
DR Orphanet; 300298; Severe congenital hypochromic anemia with ringed sideroblasts.
DR PharmGKB; PA142670863; -.
DR VEuPathDB; HostDB:ENSG00000115107; -.
DR eggNOG; ENOG502QRP3; Eukaryota.
DR GeneTree; ENSGT00390000008042; -.
DR HOGENOM; CLU_034618_1_1_1; -.
DR InParanoid; Q658P3; -.
DR OMA; WVDEEVW; -.
DR OrthoDB; 638341at2759; -.
DR PhylomeDB; Q658P3; -.
DR TreeFam; TF332031; -.
DR PathwayCommons; Q658P3; -.
DR Reactome; R-HSA-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9035034; RHOF GTPase cycle.
DR Reactome; R-HSA-917977; Transferrin endocytosis and recycling.
DR SignaLink; Q658P3; -.
DR BioGRID-ORCS; 55240; 45 hits in 1094 CRISPR screens.
DR ChiTaRS; STEAP3; human.
DR EvolutionaryTrace; Q658P3; -.
DR GeneWiki; STEAP3; -.
DR GenomeRNAi; 55240; -.
DR Pharos; Q658P3; Tbio.
DR PRO; PR:Q658P3; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q658P3; protein.
DR Bgee; ENSG00000115107; Expressed in right lobe of liver and 180 other tissues.
DR ExpressionAtlas; Q658P3; baseline and differential.
DR Genevisible; Q658P3; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005771; C:multivesicular body; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0008823; F:cupric reductase activity; IBA:GO_Central.
DR GO; GO:0052851; F:ferric-chelate reductase (NADPH) activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016723; F:oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor; TAS:Reactome.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0015677; P:copper ion import; IBA:GO_Central.
DR GO; GO:0055072; P:iron ion homeostasis; IEA:UniProtKB-KW.
DR GO; GO:0009306; P:protein secretion; IDA:MGI.
DR GO; GO:0033572; P:transferrin transport; TAS:Reactome.
DR InterPro; IPR013130; Fe3_Rdtase_TM_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR028939; P5C_Rdtase_cat_N.
DR Pfam; PF03807; F420_oxidored; 1.
DR Pfam; PF01794; Ferric_reduct; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell cycle; Copper;
KW Endosome; FAD; Flavoprotein; Glycoprotein; Heme; Ion transport; Iron;
KW Iron transport; Membrane; Metal-binding; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..488
FT /note="Metalloreductase STEAP3"
FT /id="PRO_0000285171"
FT TOPO_DOM 1..207
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 208..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 229..258
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 259..279
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 280..304
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 305..325
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..358
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 359..379
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 380..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 391..411
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 412..433
FT /note="Vesicular"
FT /evidence="ECO:0000255"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..488
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 259..407
FT /note="Ferric oxidoreductase"
FT BINDING 36..39
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:18495927,
FT ECO:0007744|PDB:2VQ3"
FT BINDING 58..59
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:18495927,
FT ECO:0007744|PDB:2VQ3"
FT BINDING 91..98
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:18495927,
FT ECO:0007744|PDB:2VQ3"
FT BINDING 116
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:18495927"
FT BINDING 151
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:18495927"
FT BINDING 152
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q687X5"
FT BINDING 160
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q687X5"
FT BINDING 281
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q687X5"
FT BINDING 302
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q687X5"
FT BINDING 316
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q687X5"
FT BINDING 378
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q687X5"
FT BINDING 395
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q687X5"
FT BINDING 409
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q687X5"
FT SITE 325..326
FT /note="Cleavage; by RHBDL4/RHBDD1"
FT /evidence="ECO:0000305"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 474
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:22624035"
FT CARBOHYD 344
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305|PubMed:22624035"
FT VAR_SEQ 1
FT /note="M -> MSHQPAVATKM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_024829"
FT VAR_SEQ 351
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10969787, ECO:0000303|Ref.5"
FT /id="VSP_024830"
FT VAR_SEQ 396..488
FT /note="SSLGFVALVLSTLHTLTYGWTRAFEESRYKFYLPPTFTLTLLVPCVVILAKA
FT LFLLPCISRRLARIRRGWERESTIKFTLPTDHALAEKTSHV -> CVATSSAGNTGSGT
FT RRPESQSQDPHLPAPHHQTSFLGPRSFCCSLVPVSTPYGHQEDLSWTR (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:10969787"
FT /id="VSP_024831"
FT VARIANT 184
FT /note="A -> T (in dbSNP:rs17013371)"
FT /id="VAR_031975"
FT MUTAGEN 256
FT /note="N->I: Inhibits glycosylation and does not inhibit
FT RHBDL4/RHBDD1-induced cleavage; when associated with A-
FT 344."
FT /evidence="ECO:0000269|PubMed:22624035"
FT MUTAGEN 325
FT /note="L->F: Strongly inhibits RHBDL4/RHBDD1-induced
FT cleavage."
FT /evidence="ECO:0000269|PubMed:22624035"
FT MUTAGEN 344
FT /note="N->I: Inhibits glycosylation and does not inhibit
FT RHBDL4/RHBDD1-induced cleavage; when associated with A-
FT 256."
FT /evidence="ECO:0000269|PubMed:22624035"
FT CONFLICT 32
FT /note="G -> S (in Ref. 3; AAL78206/AAM08128 and 6;
FT AAM45136)"
FT /evidence="ECO:0000305"
FT CONFLICT 68
FT /note="F -> Y (in Ref. 4; AAK50538 and 7; BAA91839)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="R -> G (in Ref. 3; AAL78206/AAM08128)"
FT /evidence="ECO:0000305"
FT CONFLICT 478
FT /note="D -> G (in Ref. 8; CAD97986)"
FT /evidence="ECO:0000305"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 38..49
FT /evidence="ECO:0007829|PDB:2VNS"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 61..67
FT /evidence="ECO:0007829|PDB:2VNS"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 77..80
FT /evidence="ECO:0007829|PDB:2VNS"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 93..95
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 97..102
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:2VNS"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 119..124
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 129..136
FT /evidence="ECO:0007829|PDB:2VNS"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 151..155
FT /evidence="ECO:0007829|PDB:2VNS"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 172..184
FT /evidence="ECO:0007829|PDB:2VNS"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:2VNS"
FT HELIX 198..203
FT /evidence="ECO:0007829|PDB:2VNS"
SQ SEQUENCE 488 AA; 54601 MW; C89EB0D0430F9BFB CRC64;
MPEEMDKPLI SLHLVDSDSS LAKVPDEAPK VGILGSGDFA RSLATRLVGS GFKVVVGSRN
PKRTARLFPS AAQVTFQEEA VSSPEVIFVA VFREHYSSLC SLSDQLAGKI LVDVSNPTEQ
EHLQHRESNA EYLASLFPTC TVVKAFNVIS AWTLQAGPRD GNRQVPICGD QPEAKRAVSE
MALAMGFMPV DMGSLASAWE VEAMPLRLLP AWKVPTLLAL GLFVCFYAYN FVRDVLQPYV
QESQNKFFKL PVSVVNTTLP CVAYVLLSLV YLPGVLAAAL QLRRGTKYQR FPDWLDHWLQ
HRKQIGLLSF FCAALHALYS FCLPLRRAHR YDLVNLAVKQ VLANKSHLWV EEEVWRMEIY
LSLGVLALGT LSLLAVTSLP SIANSLNWRE FSFVQSSLGF VALVLSTLHT LTYGWTRAFE
ESRYKFYLPP TFTLTLLVPC VVILAKALFL LPCISRRLAR IRRGWEREST IKFTLPTDHA
LAEKTSHV
