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Protein

Hephaestin

Gene

HEPH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May function as a ferroxidase for ferrous (II) to ferric ion (III) conversion and may be involved in copper transport and homeostasis. Implicated in iron homeostasis and may mediate iron efflux associated to ferroportin 1.

Cofactori

Cu cationBy similarityNote: Binds 6 Cu cations per monomer.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi126Copper 1; type 2By similarity1
Metal bindingi128Copper 2; type 3By similarity1
Metal bindingi186Copper 2; type 3By similarity1
Metal bindingi188Copper 3; type 3By similarity1
Metal bindingi304Copper 4; type 1By similarity1
Metal bindingi347Copper 4; type 1By similarity1
Metal bindingi352Copper 4; type 1By similarity1
Metal bindingi656Copper 5; type 1By similarity1
Metal bindingi699Copper 5; type 1By similarity1
Metal bindingi704Copper 5; type 1By similarity1
Metal bindingi709Copper 5; type 1By similarity1
Metal bindingi1000Copper 6; type 1By similarity1
Metal bindingi1003Copper 1; type 2By similarity1
Metal bindingi1005Copper 3; type 3By similarity1
Metal bindingi1045Copper 3; type 3By similarity1
Metal bindingi1046Copper 6; type 1By similarity1
Metal bindingi1047Copper 2; type 3By similarity1
Metal bindingi1051Copper 6; type 1By similarity1
Metal bindingi1056Copper 6; type 1By similarity1

GO - Molecular functioni

  • copper ion binding Source: UniProtKB
  • ferrous iron binding Source: UniProtKB
  • ferroxidase activity Source: UniProtKB

GO - Biological processi

  • cellular iron ion homeostasis Source: Reactome
  • copper ion transport Source: UniProtKB-KW
  • iron ion transport Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Copper transport, Ion transport, Iron transport, Transport

Keywords - Ligandi

Copper, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-425410. Metal ion SLC transporters.
R-HSA-917937. Iron uptake and transport.

Names & Taxonomyi

Protein namesi
Recommended name:
Hephaestin (EC:1.-.-.-)
Gene namesi
Name:HEPH
Synonyms:KIAA0698
ORF Names:UNQ2562/PRO6242
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:4866. HEPH.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 1110ExtracellularSequence analysisAdd BLAST1087
Transmembranei1111 – 1131HelicalSequence analysisAdd BLAST21
Topological domaini1132 – 1158CytoplasmicSequence analysisAdd BLAST27

GO - Cellular componenti

  • basolateral plasma membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • intracellular Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi9843.
OpenTargetsiENSG00000089472.
PharmGKBiPA29241.

Polymorphism and mutation databases

BioMutaiHEPH.
DMDMi52782976.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000000291524 – 1158HephaestinAdd BLAST1135

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi164N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi180 ↔ 206Sequence analysis
Glycosylationi236N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi285 ↔ 366Sequence analysis
Disulfide bondi534 ↔ 560Sequence analysis
Glycosylationi588N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi637 ↔ 718Sequence analysis
Glycosylationi714N-linked (GlcNAc...)Sequence analysis1
Glycosylationi758N-linked (GlcNAc...)Sequence analysis1
Glycosylationi829N-linked (GlcNAc...)Sequence analysis1
Glycosylationi873N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi877 ↔ 903Sequence analysis
Glycosylationi931N-linked (GlcNAc...)Sequence analysis1
Modified residuei1145PhosphoserineCombined sources1
Modified residuei1150PhosphoserineCombined sources1
Modified residuei1155PhosphoserineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9BQS7.
PaxDbiQ9BQS7.
PeptideAtlasiQ9BQS7.
PRIDEiQ9BQS7.

PTM databases

iPTMnetiQ9BQS7.
PhosphoSitePlusiQ9BQS7.

Expressioni

Tissue specificityi

Detected in breast, colon, bone trabecular cells and fibroblasts.

Gene expression databases

BgeeiENSG00000089472.
CleanExiHS_HEPH.
ExpressionAtlasiQ9BQS7. baseline and differential.
GenevisibleiQ9BQS7. HS.

Organism-specific databases

HPAiHPA005824.

Interactioni

Protein-protein interaction databases

BioGridi115179. 1 interactor.
STRINGi9606.ENSP00000430620.

Structurei

3D structure databases

ProteinModelPortaliQ9BQS7.
SMRiQ9BQS7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 206Plastocyanin-like 1Add BLAST183
Domaini218 – 366Plastocyanin-like 2Add BLAST149
Domaini379 – 560Plastocyanin-like 3Add BLAST182
Domaini570 – 718Plastocyanin-like 4Add BLAST149
Domaini731 – 903Plastocyanin-like 5Add BLAST173
Domaini911 – 1087Plastocyanin-like 6Add BLAST177

Sequence similaritiesi

Belongs to the multicopper oxidase family.Curated
Contains 6 plastocyanin-like domains.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1263. Eukaryota.
COG2132. LUCA.
GeneTreeiENSGT00550000074552.
HOGENOMiHOG000231499.
HOVERGENiHBG003674.
InParanoidiQ9BQS7.
KOiK14735.
OMAiLIHLKNF.
OrthoDBiEOG091G00QL.
PhylomeDBiQ9BQS7.
TreeFamiTF329807.

Family and domain databases

Gene3Di2.60.40.420. 6 hits.
InterProiIPR011706. Cu-oxidase_2.
IPR011707. Cu-oxidase_3.
IPR033138. Cu_oxidase_CS.
IPR002355. Cu_oxidase_Cu_BS.
IPR008972. Cupredoxin.
IPR027154. HEPH.
[Graphical view]
PANTHERiPTHR10127:SF622. PTHR10127:SF622. 1 hit.
PfamiPF07731. Cu-oxidase_2. 1 hit.
PF07732. Cu-oxidase_3. 2 hits.
[Graphical view]
SUPFAMiSSF49503. SSF49503. 6 hits.
PROSITEiPS00079. MULTICOPPER_OXIDASE1. 3 hits.
PS00080. MULTICOPPER_OXIDASE2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BQS7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MESGHLLWAL LFMQSLWPQL TDGATRVYYL GIRDVQWNYA PKGRNVITNQ
60 70 80 90 100
PLDSDIVASS FLKSDKNRIG GTYKKTIYKE YKDDSYTDEV AQPAWLGFLG
110 120 130 140 150
PVLQAEVGDV ILIHLKNFAT RPYTIHPHGV FYEKDSEGSL YPDGSSGPLK
160 170 180 190 200
ADDSVPPGGS HIYNWTIPEG HAPTDADPAC LTWIYHSHVD APRDIATGLI
210 220 230 240 250
GPLITCKRGA LDGNSPPQRQ DVDHDFFLLF SVVDENLSWH LNENIATYCS
260 270 280 290 300
DPASVDKEDE TFQESNRMHA INGFVFGNLP ELNMCAQKRV AWHLFGMGNE
310 320 330 340 350
IDVHTAFFHG QMLTTRGHHT DVANIFPATF VTAEMVPWEP GTWLISCQVN
360 370 380 390 400
SHFRDGMQAL YKVKSCSMAP PVDLLTGKVR QYFIEAHEIQ WDYGPMGHDG
410 420 430 440 450
STGKNLREPG SISDKFFQKS SSRIGGTYWK VRYEAFQDET FQEKMHLEED
460 470 480 490 500
RHLGILGPVI RAEVGDTIQV VFYNRASQPF SMQPHGVFYE KDYEGTVYND
510 520 530 540 550
GSSYPGLVAK PFEKVTYRWT VPPHAGPTAQ DPACLTWMYF SAADPIRDTN
560 570 580 590 600
SGLVGPLLVC RAGALGADGK QKGVDKEFFL LFTVLDENKS WYSNANQAAA
610 620 630 640 650
MLDFRLLSED IEGFQDSNRM HAINGFLFSN LPRLDMCKGD TVAWHLLGLG
660 670 680 690 700
TETDVHGVMF QGNTVQLQGM RKGAAMLFPH TFVMAIMQPD NLGTFEIYCQ
710 720 730 740 750
AGSHREAGMR AIYNVSQCPG HQATPRQRYQ AARIYYIMAE EVEWDYCPDR
760 770 780 790 800
SWEREWHNQS EKDSYGYIFL SNKDGLLGSR YKKAVFREYT DGTFRIPRPR
810 820 830 840 850
TGPEEHLGIL GPLIKGEVGD ILTVVFKNNA SRPYSVHAHG VLESTTVWPL
860 870 880 890 900
AAEPGEVVTY QWNIPERSGP GPNDSACVSW IYYSAVDPIK DMYSGLVGPL
910 920 930 940 950
AICQKGILEP HGGRSDMDRE FALLFLIFDE NKSWYLEENV ATHGSQDPGS
960 970 980 990 1000
INLQDETFLE SNKMHAINGK LYANLRGLTM YQGERVAWYM LAMGQDVDLH
1010 1020 1030 1040 1050
TIHFHAESFL YRNGENYRAD VVDLFPGTFE VVEMVASNPG TWLMHCHVTD
1060 1070 1080 1090 1100
HVHAGMETLF TVFSRTEHLS PLTVITKETE KAVPPRDIEE GNVKMLGMQI
1110 1120 1130 1140 1150
PIKNVEMLAS VLVAISVTLL LVVLALGGVV WYQHRQRKLR RNRRSILDDS

FKLLSFKQ
Length:1,158
Mass (Da):130,449
Last modified:September 27, 2004 - v3
Checksum:iCD032199E2E2868D
GO
Isoform 2 (identifier: Q9BQS7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1082-1082: Missing.

Show »
Length:1,157
Mass (Da):130,378
Checksum:i3DCFE053093BFA7D
GO
Isoform 3 (identifier: Q9BQS7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MTQTLPYHLSLLNVLFPGPCSRHFKFRRGKCAQPAWRKVSAPSQDLLITKVMWAM

Note: No experimental confirmation available.
Show »
Length:1,212
Mass (Da):136,658
Checksum:i9C03D79DAE69BA8C
GO
Isoform 4 (identifier: Q9BQS7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-267: Missing.

Note: No experimental confirmation available.
Show »
Length:891
Mass (Da):100,624
Checksum:iAB70D0436109C5B2
GO

Sequence cautioni

The sequence AAQ89349 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence EAX05385 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence EAX05388 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55 – 56DI → QR in BAA31673 (PubMed:9734811).Curated2
Sequence conflicti222V → T in CAC35365 (PubMed:11932491).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_024379595A → T.Corresponds to variant rs17216603dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0473321 – 267Missing in isoform 4. CuratedAdd BLAST267
Alternative sequenceiVSP_0473311M → MTQTLPYHLSLLNVLFPGPC SRHFKFRRGKCAQPAWRKVS APSQDLLITKVMWAM in isoform 3. Curated1
Alternative sequenceiVSP_0116271082Missing in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ296162 mRNA. Translation: CAC35365.2.
AF148860 mRNA. Translation: AAK08131.1.
AY358990 mRNA. Translation: AAQ89349.1. Different initiation.
AL030998 Genomic DNA. No translation available.
AL157698 Genomic DNA. No translation available.
CH471132 Genomic DNA. Translation: EAX05384.1.
CH471132 Genomic DNA. Translation: EAX05385.1. Different initiation.
CH471132 Genomic DNA. Translation: EAX05386.1.
CH471132 Genomic DNA. Translation: EAX05388.1. Different initiation.
BC011561 mRNA. Translation: AAH11561.1.
AB014598 mRNA. Translation: BAA31673.2.
CCDSiCCDS14384.3. [Q9BQS7-3]
CCDS14385.1. [Q9BQS7-4]
RefSeqiNP_001124332.1. NM_001130860.3.
NP_001269070.1. NM_001282141.1.
NP_055614.1. NM_014799.3. [Q9BQS7-4]
NP_620074.3. NM_138737.4. [Q9BQS7-3]
XP_006724785.1. XM_006724722.1.
UniGeneiHs.31720.

Genome annotation databases

EnsembliENST00000336279; ENSP00000337418; ENSG00000089472. [Q9BQS7-4]
ENST00000343002; ENSP00000343939; ENSG00000089472. [Q9BQS7-1]
ENST00000519389; ENSP00000430620; ENSG00000089472. [Q9BQS7-3]
GeneIDi9843.
KEGGihsa:9843.
UCSCiuc004dwn.5. human. [Q9BQS7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Hephaestin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ296162 mRNA. Translation: CAC35365.2.
AF148860 mRNA. Translation: AAK08131.1.
AY358990 mRNA. Translation: AAQ89349.1. Different initiation.
AL030998 Genomic DNA. No translation available.
AL157698 Genomic DNA. No translation available.
CH471132 Genomic DNA. Translation: EAX05384.1.
CH471132 Genomic DNA. Translation: EAX05385.1. Different initiation.
CH471132 Genomic DNA. Translation: EAX05386.1.
CH471132 Genomic DNA. Translation: EAX05388.1. Different initiation.
BC011561 mRNA. Translation: AAH11561.1.
AB014598 mRNA. Translation: BAA31673.2.
CCDSiCCDS14384.3. [Q9BQS7-3]
CCDS14385.1. [Q9BQS7-4]
RefSeqiNP_001124332.1. NM_001130860.3.
NP_001269070.1. NM_001282141.1.
NP_055614.1. NM_014799.3. [Q9BQS7-4]
NP_620074.3. NM_138737.4. [Q9BQS7-3]
XP_006724785.1. XM_006724722.1.
UniGeneiHs.31720.

3D structure databases

ProteinModelPortaliQ9BQS7.
SMRiQ9BQS7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115179. 1 interactor.
STRINGi9606.ENSP00000430620.

PTM databases

iPTMnetiQ9BQS7.
PhosphoSitePlusiQ9BQS7.

Polymorphism and mutation databases

BioMutaiHEPH.
DMDMi52782976.

Proteomic databases

MaxQBiQ9BQS7.
PaxDbiQ9BQS7.
PeptideAtlasiQ9BQS7.
PRIDEiQ9BQS7.

Protocols and materials databases

DNASUi9843.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336279; ENSP00000337418; ENSG00000089472. [Q9BQS7-4]
ENST00000343002; ENSP00000343939; ENSG00000089472. [Q9BQS7-1]
ENST00000519389; ENSP00000430620; ENSG00000089472. [Q9BQS7-3]
GeneIDi9843.
KEGGihsa:9843.
UCSCiuc004dwn.5. human. [Q9BQS7-1]

Organism-specific databases

CTDi9843.
DisGeNETi9843.
GeneCardsiHEPH.
H-InvDBHIX0016844.
HGNCiHGNC:4866. HEPH.
HPAiHPA005824.
MIMi300167. gene.
neXtProtiNX_Q9BQS7.
OpenTargetsiENSG00000089472.
PharmGKBiPA29241.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1263. Eukaryota.
COG2132. LUCA.
GeneTreeiENSGT00550000074552.
HOGENOMiHOG000231499.
HOVERGENiHBG003674.
InParanoidiQ9BQS7.
KOiK14735.
OMAiLIHLKNF.
OrthoDBiEOG091G00QL.
PhylomeDBiQ9BQS7.
TreeFamiTF329807.

Enzyme and pathway databases

ReactomeiR-HSA-425410. Metal ion SLC transporters.
R-HSA-917937. Iron uptake and transport.

Miscellaneous databases

GenomeRNAii9843.
PROiQ9BQS7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000089472.
CleanExiHS_HEPH.
ExpressionAtlasiQ9BQS7. baseline and differential.
GenevisibleiQ9BQS7. HS.

Family and domain databases

Gene3Di2.60.40.420. 6 hits.
InterProiIPR011706. Cu-oxidase_2.
IPR011707. Cu-oxidase_3.
IPR033138. Cu_oxidase_CS.
IPR002355. Cu_oxidase_Cu_BS.
IPR008972. Cupredoxin.
IPR027154. HEPH.
[Graphical view]
PANTHERiPTHR10127:SF622. PTHR10127:SF622. 1 hit.
PfamiPF07731. Cu-oxidase_2. 1 hit.
PF07732. Cu-oxidase_3. 2 hits.
[Graphical view]
SUPFAMiSSF49503. SSF49503. 6 hits.
PROSITEiPS00079. MULTICOPPER_OXIDASE1. 3 hits.
PS00080. MULTICOPPER_OXIDASE2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHEPH_HUMAN
AccessioniPrimary (citable) accession number: Q9BQS7
Secondary accession number(s): B1AJX8
, D3DVT7, E9PHN8, O75180, Q6UW45, Q9C058
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 27, 2004
Last sequence update: September 27, 2004
Last modified: November 2, 2016
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.