HEPH_RAT
ID HEPH_RAT Reviewed; 1157 AA.
AC Q920H8;
DT 27-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Hephaestin;
DE EC=1.-.-.-;
DE Flags: Precursor;
GN Name=Heph;
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], AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=11557513; DOI=10.1152/ajpgi.2001.281.4.g931;
RA Frazer D.M., Vulpe C.D., McKie A.T., Wilkins S.J., Trinder D.,
RA Cleghorn G.J., Anderson G.J.;
RT "Cloning and gastrointestinal expression of rat hephaestin: relationship to
RT other iron transport proteins.";
RL Am. J. Physiol. 281:G931-G939(2001).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1144 AND SER-1149, 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: May function as a ferroxidase for ferrous (II) to ferric ion
CC (III) conversion and may be involved in copper transport and
CC homeostasis. Implicated in iron homeostasis and may mediate iron efflux
CC associated to ferroportin 1 (By similarity). {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378; Evidence={ECO:0000250};
CC Note=Binds 6 Cu cations per monomer. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in small intestine and colon.
CC {ECO:0000269|PubMed:11557513}.
CC -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
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DR EMBL; AF246120; AAL08217.1; -; mRNA.
DR RefSeq; NP_579838.1; NM_133304.1.
DR RefSeq; XP_006257108.1; XM_006257046.3.
DR RefSeq; XP_006257110.1; XM_006257048.3.
DR RefSeq; XP_006257111.1; XM_006257049.3.
DR RefSeq; XP_008771470.1; XM_008773248.1.
DR RefSeq; XP_008771471.1; XM_008773249.2.
DR RefSeq; XP_008771472.1; XM_008773250.2.
DR AlphaFoldDB; Q920H8; -.
DR SMR; Q920H8; -.
DR STRING; 10116.ENSRNOP00000017312; -.
DR GlyGen; Q920H8; 8 sites.
DR iPTMnet; Q920H8; -.
DR PhosphoSitePlus; Q920H8; -.
DR PaxDb; Q920H8; -.
DR Ensembl; ENSRNOT00000017312; ENSRNOP00000017312; ENSRNOG00000012294.
DR GeneID; 117240; -.
DR KEGG; rno:117240; -.
DR CTD; 9843; -.
DR RGD; 71060; Heph.
DR eggNOG; KOG1263; Eukaryota.
DR GeneTree; ENSGT00940000158517; -.
DR HOGENOM; CLU_005569_0_0_1; -.
DR InParanoid; Q920H8; -.
DR OMA; YCQEGSH; -.
DR OrthoDB; 454773at2759; -.
DR PhylomeDB; Q920H8; -.
DR TreeFam; TF329807; -.
DR Reactome; R-RNO-425410; Metal ion SLC transporters.
DR Reactome; R-RNO-917937; Iron uptake and transport.
DR PRO; PR:Q920H8; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000012294; Expressed in duodenum and 18 other tissues.
DR Genevisible; Q920H8; RN.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0005507; F:copper ion binding; ISO:RGD.
DR GO; GO:0008198; F:ferrous iron binding; ISO:RGD.
DR GO; GO:0004322; F:ferroxidase activity; ISO:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:InterPro.
DR GO; GO:0006825; P:copper ion transport; IEA:UniProtKB-KW.
DR GO; GO:0030218; P:erythrocyte differentiation; ISO:RGD.
DR GO; GO:0055072; P:iron ion homeostasis; IBA:GO_Central.
DR GO; GO:0006826; P:iron ion transport; ISO:RGD.
DR Gene3D; 2.60.40.420; -; 3.
DR InterPro; IPR011706; Cu-oxidase_C.
DR InterPro; IPR045087; Cu-oxidase_fam.
DR InterPro; IPR011707; Cu-oxidase_N.
DR InterPro; IPR033138; Cu_oxidase_CS.
DR InterPro; IPR002355; Cu_oxidase_Cu_BS.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR027154; HEPH.
DR PANTHER; PTHR11709; PTHR11709; 5.
DR PANTHER; PTHR11709:SF221; PTHR11709:SF221; 5.
DR Pfam; PF07731; Cu-oxidase_2; 1.
DR Pfam; PF07732; Cu-oxidase_3; 3.
DR SUPFAM; SSF49503; SSF49503; 6.
DR PROSITE; PS00079; MULTICOPPER_OXIDASE1; 3.
DR PROSITE; PS00080; MULTICOPPER_OXIDASE2; 1.
PE 1: Evidence at protein level;
KW Copper; Copper transport; Disulfide bond; Glycoprotein; Ion transport;
KW Iron; Iron transport; Membrane; Metal-binding; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1157
FT /note="Hephaestin"
FT /id="PRO_0000002917"
FT TOPO_DOM 24..1109
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1110..1130
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1131..1157
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..206
FT /note="Plastocyanin-like 1"
FT DOMAIN 218..366
FT /note="Plastocyanin-like 2"
FT DOMAIN 379..559
FT /note="Plastocyanin-like 3"
FT DOMAIN 569..717
FT /note="Plastocyanin-like 4"
FT DOMAIN 730..902
FT /note="Plastocyanin-like 5"
FT DOMAIN 910..1086
FT /note="Plastocyanin-like 6"
FT BINDING 126
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /note="type 2 copper site"
FT /evidence="ECO:0000250"
FT BINDING 128
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /note="type 3 copper site"
FT /evidence="ECO:0000250"
FT BINDING 186
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /note="type 3 copper site"
FT /evidence="ECO:0000250"
FT BINDING 188
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="3"
FT /note="type 3 copper site"
FT /evidence="ECO:0000250"
FT BINDING 304
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="4"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 347
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="4"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 352
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="4"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 655
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="5"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 698
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="5"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 703
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="5"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 708
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="5"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 999
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="6"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 1002
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="1"
FT /note="type 2 copper site"
FT /evidence="ECO:0000250"
FT BINDING 1004
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="3"
FT /note="type 3 copper site"
FT /evidence="ECO:0000250"
FT BINDING 1044
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="3"
FT /note="type 3 copper site"
FT /evidence="ECO:0000250"
FT BINDING 1045
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="6"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 1046
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="2"
FT /note="type 3 copper site"
FT /evidence="ECO:0000250"
FT BINDING 1050
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="6"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT BINDING 1055
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /ligand_label="6"
FT /note="type 1 copper site"
FT /evidence="ECO:0000250"
FT MOD_RES 1144
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1149
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1154
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0Z4"
FT CARBOHYD 49
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 587
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 713
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 757
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 930
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 180..206
FT /evidence="ECO:0000255"
FT DISULFID 285..366
FT /evidence="ECO:0000255"
FT DISULFID 533..559
FT /evidence="ECO:0000255"
FT DISULFID 636..717
FT /evidence="ECO:0000255"
FT DISULFID 876..902
FT /evidence="ECO:0000255"
SQ SEQUENCE 1157 AA; 129593 MW; 0C626FA3E2F51DE2 CRC64;
MKAGHLLWAL LLMHSLCSLP TDGAIRNYYL GIQDIQWNYA PKGRNVITNQ TLNNDTVASS
FLKSGKNRIG GTYKKTVYKE YSDGTYTNEI AKPAWLGFLG PLLKAEMGDV ILIHLKNFAS
RPYTIHPHGV FYEKDSEGSL YPDGSSGYLK ADDSVPPGGS HVYNWSIPEG HAPTEADPAC
LTWIYHSHVD APRDIATGLI GPLITCKRGT LDGNSPPQRK DVDHNFFLLF SVIDENLSWH
LDDNIATYCS DPASVDKEDG PFQDSNRMHA INGFVFGNLP ELSMCAQKHV AWHLFGMGNE
IDVHTAFFHG QTLSIRGHRT DVAHIFPATF VTAEMVPQKS GTWLISCVVN SHLKSGMQAF
YKVDSCSMDP PVEQLTGKVR QYFIQAHEIQ WDYGPIGHDG RTGKSLREPG SGPDKYFQKS
SSRIGGTYWK VRYEAFQDET FQERLHQEEE THLGILGPVI RAEVGDTIQV VFYNRASQPF
SIQPHGVFYE KSSEGTVYND GTSYPKVAKS FEKVTYYWTV PPHAGPTAED PACLTWMYFS
AADPTRDTNS GLVGPLLVCK AGALGEDGKQ KGVDKEFFLL FTIFDENESW YNNANQAAGM
LDSRLLSEDV EGFEDSNRMH AINGFLFSNL PRLDICKGDT VAWHLLGLGT ENDVHGVMFE
GNTLQLQGMR KSAAMLFPHT FVTAIMQPDN PGIFEIYCQA GSHREAGMQA IYNVSQCSSH
QDSPRQHYQA SRVYYIMAEE IEWDYCPDRS WELEWYNTSE KDSYGHVFLS NKDGLLGSKY
KKAVFREYTD GTFRIPQPRS GPEEHLGILG PLIRGEVGDI LTVVFKNKAS RPYSIHAHGV
LESSTGWPQA AEPGEVLTYQ WNIPERSGPG PSDSACVSWI YYSAVDPIKD MYSGLVGPLV
ICRNGILEPN GGRNDMDREF ALLFLIFDEN QSWYLKENIA TYGPQETSHV NLQDATFLES
NKMHAINGKL YANLRGLTVY QGERVAWYML AMGQDTDIHT VHFHAESFLY QNGHSYRADV
VDLFPGTFEV VEMVASNPGA WLMHCHVTDH VHAGMETIFT VLSHEEHFST MTTITKEIGK
AVILQNIGEG NVKMLGMNIP VKNVEILSSA LIAICVVLLL IALALGGVVW YQHRQRKLRR
NRRSILDDSF KLLSLKQ
