STEA3_RAT
ID STEA3_RAT Reviewed; 488 AA.
AC Q5RKL5; Q99P41;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Metalloreductase STEAP3;
DE EC=1.16.1.-;
DE AltName: Full=Six-transmembrane epithelial antigen of prostate 3;
DE AltName: Full=pHyde;
GN Name=Steap3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Prostatic carcinoma;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [3]
RP POSSIBLE FUNCTION.
RX PubMed=11593405; DOI=10.1038/sj.onc.1204831;
RA Zhang X., Steiner M.S., Rinaldy A., Lu Y.;
RT "Apoptosis induction in prostate cancer cells by a novel gene product,
RT pHyde, involves caspase-3.";
RL Oncogene 20:5982-5990(2001).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17 AND SER-20, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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+). Also mediates reduction
CC of Cu(2+) to Cu(1+), suggesting that it participates in copper
CC homeostasis. Uses NADP(+) as acceptor. Indirectly involved in exosome
CC secretion by facilitating the secretion of proteins such as TCTP (By
CC similarity). May play a role downstream of p53/TP53 to interface
CC apoptosis and cell cycle progression. {ECO:0000250}.
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 TCTP
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250}; Multi-pass
CC membrane protein {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced
CC cleavage occurs at multiple sites in a glycosylation-independent manner
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the STEAP family. {ECO:0000305}.
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DR EMBL; AF335281; AAK00361.1; -; mRNA.
DR EMBL; AF238865; AAL78207.1; -; mRNA.
DR EMBL; BC085696; AAH85696.1; -; mRNA.
DR RefSeq; NP_579848.1; NM_133314.1.
DR AlphaFoldDB; Q5RKL5; -.
DR SMR; Q5RKL5; -.
DR STRING; 10116.ENSRNOP00000064137; -.
DR GlyGen; Q5RKL5; 1 site.
DR iPTMnet; Q5RKL5; -.
DR PhosphoSitePlus; Q5RKL5; -.
DR PaxDb; Q5RKL5; -.
DR PRIDE; Q5RKL5; -.
DR Ensembl; ENSRNOT00000104769; ENSRNOP00000086517; ENSRNOG00000049471.
DR GeneID; 170824; -.
DR KEGG; rno:170824; -.
DR CTD; 55240; -.
DR RGD; 708552; Steap3.
DR eggNOG; ENOG502QRP3; Eukaryota.
DR GeneTree; ENSGT00390000008042; -.
DR HOGENOM; CLU_034618_1_1_1; -.
DR InParanoid; Q5RKL5; -.
DR OrthoDB; 638341at2759; -.
DR PhylomeDB; Q5RKL5; -.
DR Reactome; R-RNO-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013405; RHOD GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9035034; RHOF GTPase cycle.
DR Reactome; R-RNO-917977; Transferrin endocytosis and recycling.
DR PRO; PR:Q5RKL5; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Genevisible; Q5RKL5; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005771; C:multivesicular body; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0008823; F:cupric reductase activity; ISO:RGD.
DR GO; GO:0052851; F:ferric-chelate reductase (NADPH) activity; ISO:RGD.
DR GO; GO:0000293; F:ferric-chelate reductase activity; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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; ISO:RGD.
DR GO; GO:1990182; P:exosomal secretion; ISO:RGD.
DR GO; GO:0033212; P:iron import into cell; ISO:RGD.
DR GO; GO:0006826; P:iron ion transport; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
DR GO; GO:1902167; P:positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
DR GO; GO:0009306; P:protein secretion; ISS:UniProtKB.
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 Apoptosis; Cell cycle; Copper; Endosome; FAD; Flavoprotein; Glycoprotein;
KW Heme; Ion transport; Iron; Iron transport; Membrane; Metal-binding; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..488
FT /note="Metalloreductase STEAP3"
FT /id="PRO_0000285173"
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:0000250|UniProtKB:Q658P3"
FT BINDING 58..59
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q658P3"
FT BINDING 91..98
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q658P3"
FT BINDING 116
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q658P3"
FT BINDING 151
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q658P3"
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:0000250"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q658P3"
FT MOD_RES 17
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q658P3"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 53
FT /note="S -> F (in Ref. 1; AAL78207/AAK00361)"
FT /evidence="ECO:0000305"
FT CONFLICT 223..226
FT /note="FVCF -> STQS (in Ref. 1; AAL78207/AAK00361)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="L -> I (in Ref. 1; AAL78207/AAK00361)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 488 AA; 54674 MW; 686E91B7DF2B88B6 CRC64;
MSGEMDKPLI SRRLVDSDGS LAEVPKEAPK VGILGSGDFA RSLATRLVGS GFSVVVGSRN
PKRTAGLFPS LAQVTFQEEA VSSPEVIFVA VFREHYSSLC SLADQLAGKI LVDVSNPTEK
ERLQHRQSNA EYLASLFPAC TVVKAFNVIS AWALQAGPRD GNRQVLICGD QLEAKHTVSE
MARAMGFTPL DMGSLASARE VEAIPLRLLP SWKVPTLLAL GLFVCFYAYN FIRDVLQPYI
RKDENKFYKM PLSVVNTTLP CVAYVLLSLV YLPGVLAAAL QLRRGTKYQR FPDWLDHWLQ
HRKQIGLLSF FFAMLHALYS FCLPLRRSHR YDLVNLAVKQ VLANKSRLWV EEEVWRMEIY
LSLGVLALGM LSLLAVTSIP SIANSLNWKE FSFVQSTLGF VALMLSTMHT LTYGWTRAFE
ENHYKFYLPP TFTLTLLLPC VIILAKGLFL LPCLSHRLTK IRRGWERDGA VKFMLPAGHT
QGEKTSHV
