HPHL1_MOUSE
ID HPHL1_MOUSE Reviewed; 1159 AA.
AC Q3V1H3;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Ferroxidase HEPHL1 {ECO:0000250|UniProtKB:Q6MZM0};
DE EC=1.16.3.1 {ECO:0000250|UniProtKB:Q6MZM0};
DE AltName: Full=Hephaestin-like protein 1 {ECO:0000250|UniProtKB:Q6MZM0};
DE Flags: Precursor;
GN Name=Hephl1; Synonyms=Gm509;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP INVOLVEMENT IN CURLY WHISKERS PHENOTYPE.
RX PubMed=31293895; DOI=10.1016/j.ymgmr.2019.100478;
RA Eragene S., Stewart J.J., Samuel-Constanzo J.I., Tan T., Esgdaille N.Z.,
RA Bigiarelli K.J., DaCosta V.D., Jimenez H., King T.R.;
RT "The mouse curly whiskers (cw) mutations are recessive alleles of
RT hephaestin-like 1 (Hephl1).";
RL Mol. Genet. Metab. Rep. 20:100478-100478(2019).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=31125343; DOI=10.1371/journal.pgen.1008143;
RA Sharma P., Reichert M., Lu Y., Markello T.C., Adams D.R., Steinbach P.J.,
RA Fuqua B.K., Parisi X., Kaler S.G., Vulpe C.D., Anderson G.J., Gahl W.A.,
RA Malicdan M.C.V.;
RT "Biallelic HEPHL1 variants impair ferroxidase activity and cause an
RT abnormal hair phenotype.";
RL PLoS Genet. 15:E1008143-E1008143(2019).
CC -!- FUNCTION: Is a copper-binding glycoprotein with ferroxidase activity.
CC It oxidizes Fe(2+) to Fe(3+) without releasing radical oxygen species.
CC May be involved in the regulation of intracellular iron content.
CC {ECO:0000250|UniProtKB:Q6MZM0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 Fe(2+) + 4 H(+) + O2 = 4 Fe(3+) + 2 H2O;
CC Xref=Rhea:RHEA:11148, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034; EC=1.16.3.1;
CC Evidence={ECO:0000250|UniProtKB:Q6MZM0};
CC -!- COFACTOR:
CC Name=Cu cation; Xref=ChEBI:CHEBI:23378;
CC Evidence={ECO:0000250|UniProtKB:Q6MZM0};
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 -!- DISEASE: Note=Defects in HEPHL1 are the cause of the curly whiskers
CC phenotype (cw). Curly whiskers mice carry a recessive mutation that
CC alters splicing and causes omission of exon 11 from the mature
CC transcript. The cw phenotype is characterized by kinky, brittle
CC vibrissae. {ECO:0000269|PubMed:31293895}.
CC -!- DISRUPTION PHENOTYPE: HEPHL1 knockdown mice exhibit short and curled
CC whiskers. {ECO:0000269|PubMed:31125343}.
CC -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE21178.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK132457; BAE21178.1; ALT_INIT; mRNA.
DR EMBL; AC154295; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC156500; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS52725.1; -.
DR RefSeq; NP_001158269.1; NM_001164797.1.
DR AlphaFoldDB; Q3V1H3; -.
DR SMR; Q3V1H3; -.
DR BioGRID; 232682; 1.
DR STRING; 10090.ENSMUSP00000124518; -.
DR GlyGen; Q3V1H3; 6 sites.
DR PhosphoSitePlus; Q3V1H3; -.
DR EPD; Q3V1H3; -.
DR MaxQB; Q3V1H3; -.
DR PaxDb; Q3V1H3; -.
DR PRIDE; Q3V1H3; -.
DR ProteomicsDB; 273166; -.
DR Antibodypedia; 31604; 65 antibodies from 13 providers.
DR Ensembl; ENSMUST00000159985; ENSMUSP00000124518; ENSMUSG00000031936.
DR GeneID; 244698; -.
DR KEGG; mmu:244698; -.
DR UCSC; uc009ofj.2; mouse.
DR CTD; 341208; -.
DR MGI; MGI:2685355; Hephl1.
DR VEuPathDB; HostDB:ENSMUSG00000031936; -.
DR eggNOG; KOG1263; Eukaryota.
DR GeneTree; ENSGT00940000157994; -.
DR HOGENOM; CLU_005569_0_0_1; -.
DR InParanoid; Q3V1H3; -.
DR OMA; PEPDMCV; -.
DR OrthoDB; 454773at2759; -.
DR PhylomeDB; Q3V1H3; -.
DR TreeFam; TF329807; -.
DR BioGRID-ORCS; 244698; 4 hits in 74 CRISPR screens.
DR PRO; PR:Q3V1H3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q3V1H3; protein.
DR Bgee; ENSMUSG00000031936; Expressed in skin of abdomen and 29 other tissues.
DR Genevisible; Q3V1H3; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0004322; F:ferroxidase activity; ISS:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISS:UniProtKB.
DR GO; GO:0006825; P:copper ion transport; IEA:UniProtKB-KW.
DR GO; GO:0055072; P:iron ion homeostasis; ISO:MGI.
DR GO; GO:0006826; P:iron ion transport; IBA:GO_Central.
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 PANTHER; PTHR11709; PTHR11709; 3.
DR Pfam; PF07731; Cu-oxidase_2; 2.
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 2: Evidence at transcript level;
KW Copper; Copper transport; Disulfide bond; Glycoprotein; Ion transport;
KW Membrane; Metal-binding; Oxidoreductase; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1159
FT /note="Ferroxidase HEPHL1"
FT /id="PRO_0000346772"
FT TOPO_DOM 24..1114
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1115..1135
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1136..1159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 24..206
FT /note="Plastocyanin-like 1"
FT DOMAIN 217..365
FT /note="Plastocyanin-like 2"
FT DOMAIN 378..560
FT /note="Plastocyanin-like 3"
FT DOMAIN 570..718
FT /note="Plastocyanin-like 4"
FT DOMAIN 730..906
FT /note="Plastocyanin-like 5"
FT DOMAIN 914..1092
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 303
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 346
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 351
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 656
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 699
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 704
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 709
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 1002
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 1005
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 1007
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 1047
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 1048
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 1049
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 1053
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 1058
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 CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q6MZM0"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q6MZM0"
FT CARBOHYD 588
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 771
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q6MZM0"
FT CARBOHYD 934
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 180..206
FT /evidence="ECO:0000255"
FT DISULFID 284..365
FT /evidence="ECO:0000255"
FT DISULFID 534..560
FT /evidence="ECO:0000255"
FT DISULFID 637..718
FT /evidence="ECO:0000255"
FT DISULFID 880..906
FT /evidence="ECO:0000255"
SQ SEQUENCE 1159 AA; 130888 MW; 3EC317CFF861E96C CRC64;
MFLKQPGGCI LLQFLGLLGL VGAVTRTYYI GIVEEYWNYV PQGKDVITGK SFSEDKLATL
FLERGPNRIG GIYKKAVYRH FTDGSYSTEI PKPPWLGFLG PILRAEVGDV IVIHLMNFAS
RPFSLHPHGV FYDKDSEGAL YPDGTSGRNK EDDMVPPGKN YTYVWPVREE YAPAPADANC
LTWVYHSHID APKDICSGLI GPLLVCKEGV LNRYSGMRTD VDREFVIMFT LVDENQSWYL
DDNIKQFCTN PNSVDKSDAV FQRSNKMHAL NGFLFGNMPE PEMCVGESVS WHLFGMGNEI
DIHSIYFYGN TFITRGHRAD VVNLFPATFL TTEMIVENPG KWMITCQVSD HLQAGMLGQY
SVGNCRGNAP HPKVQGQQRR YFIAAEKVLW DYGPQGYDKF TGFPLNTSGS DSAVYFTQAD
NRIGGKYWKA RYTEYVDATF SRRKMPSDSE AHLGILGPVI KAEVGDILLV TFANKADKVY
SILPHGVFYD KASDAAPNVD GFLKPGAHVK PGETFTYRWT VPESVSPTDE DPPCLTYLYF
SAVQPIKDTS AGLVGPLLVC KKGTLNADGT QKGIDKEFYL LFTVFDENFS SYLDENIKKF
TWHPFSVDKE DKEFVKSNRM HAVNGYMYGS QPGLSMCKKD RVSWHLIGMG TDTDMHGVYF
QGNTIHLRGT HRDSLALFPH MATTAYMQPD HSGIFKVFCS TLPHFTRGMG QIYEISSCGN
RDPSEPPYGM LRTFFIAAEE VEWDYAPNKN WEFEKQHLDA GGERHGDIFM NHTENWIGSQ
YRKVVYREYT NGEFVEIKAR PPQEEHLQLL GPMIHAEVGD SILIIFKNKA SRPYSIAAQG
VEDSNNGKLL NVPVTKPGEI KTYRWNVPKR SGPGPSDPNC IPWVYFSTAN FVKDTYSGLM
GPLITCREGV LNEKGRRSDV DYEFALLFLV FNENESWYLD DNIKKYLNKD PRDFKHTDDF
EESNKMHAIN GKIFGNLPGL IMTEDSMTNW YLLGIGSEVD IHTIHYHAES FLFKIDKSYR
EDVYDLFPGT FQTIELFADH PGTWLLHCHV SDHIHAGMET TYTVLRNIDN RIPYSTKTPS
GAGSHAVTVP SQEQPGKEEL YFFGKNLRPR GAKAALVILF ILGLLLLVAT VVLALRLRSS
RRQMAYREVQ SCALPTDAL
