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O43323

- DHH_HUMAN

UniProt

O43323 - DHH_HUMAN

Protein

Desert hedgehog protein

Gene

DHH

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 1 (01 Jun 1998)
      Previous versions | rss
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    Functioni

    Intercellular signal essential for a variety of patterning events during development. May function as a spermatocyte survival factor in the testes. Essential for testes development.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi90 – 901Calcium 1
    Metal bindingi91 – 911Calcium 1
    Metal bindingi91 – 911Calcium 2
    Metal bindingi96 – 961Calcium 1
    Metal bindingi126 – 1261Calcium 1; via carbonyl oxygen
    Metal bindingi127 – 1271Calcium 1
    Metal bindingi127 – 1271Calcium 2
    Metal bindingi130 – 1301Calcium 2
    Metal bindingi132 – 1321Calcium 2
    Metal bindingi141 – 1411Zinc
    Metal bindingi148 – 1481Zinc
    Metal bindingi183 – 1831Zinc
    Sitei198 – 1992Cleavage; by autolysisBy similarity
    Sitei244 – 2441Involved in cholesterol transferBy similarity
    Sitei268 – 2681Involved in auto-cleavageBy similarity
    Sitei271 – 2711Essential for auto-cleavageBy similarity

    GO - Molecular functioni

    1. calcium ion binding Source: UniProtKB
    2. peptidase activity Source: UniProtKB-KW
    3. protein binding Source: BHF-UCL
    4. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. cell-cell signaling Source: InterPro
    2. Leydig cell differentiation Source: Ensembl
    3. male sex determination Source: Ensembl
    4. myelination Source: Ensembl
    5. regulation of steroid biosynthetic process Source: Ensembl
    6. response to estradiol Source: Ensembl
    7. spermatid development Source: Ensembl

    Keywords - Molecular functioni

    Developmental protein, Hydrolase, Protease

    Keywords - Ligandi

    Calcium, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
    SignaLinkiO43323.

    Protein family/group databases

    MEROPSiC46.004.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Desert hedgehog protein
    Short name:
    DHH
    Alternative name(s):
    HHG-3
    Cleaved into the following 2 chains:
    Gene namesi
    Name:DHH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:2865. DHH.

    Subcellular locationi

    Chain Desert hedgehog protein N-product : Cell membrane By similarity; Lipid-anchor By similarity; Extracellular side By similarity
    Note: The N-terminal peptide remains associated with the cell surface.By similarity
    Chain Desert hedgehog protein C-product : Secretedextracellular space By similarity
    Note: The C-terminal peptide diffuses from the cell.By similarity

    GO - Cellular componenti

    1. extracellular space Source: UniProtKB-SubCell
    2. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:607080]: Characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.1 Publication
    Note: The disease may be caused by mutations affecting the gene represented in this entry.
    Complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:233420]: Type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be non-functional streaks.1 Publication
    Note: The disease may be caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti162 – 1621L → P in GDXYM. 1 Publication
    VAR_054873

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi233420. phenotype.
    607080. phenotype.
    Orphaneti242. 46,XY complete gonadal dysgenesis.
    168563. 46,XY gonadal dysgenesis - motor and sensory neuropathy.
    PharmGKBiPA27326.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2222Sequence AnalysisAdd
    BLAST
    Chaini23 – 396374Desert hedgehog proteinPRO_0000013244Add
    BLAST
    Chaini23 – 198176Desert hedgehog protein N-productPRO_0000013245Add
    BLAST
    Chaini199 – 396198Desert hedgehog protein C-productPRO_0000013246Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi23 – 231N-palmitoyl cysteineBy similarity
    Lipidationi198 – 1981Cholesterol glycine esterBy similarity

    Post-translational modificationi

    The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity. Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (N-product). This covalent modification appears to play an essential role in restricting the spatial distribution of the protein activity to the cell surface. The N-product is the active species in both local and long-range signaling, whereas the C-product has no signaling activity By similarity.By similarity

    Keywords - PTMi

    Autocatalytic cleavage, Lipoprotein, Palmitate

    Proteomic databases

    PaxDbiO43323.
    PRIDEiO43323.

    Expressioni

    Gene expression databases

    ArrayExpressiO43323.
    BgeeiO43323.
    CleanExiHS_DHH.
    GenevestigatoriO43323.

    Organism-specific databases

    HPAiCAB034386.

    Interactioni

    Subunit structurei

    Interacts with BOC and CDON. Interacts with HHIP.2 Publications

    Protein-protein interaction databases

    BioGridi119151. 1 interaction.
    DIPiDIP-48538N.
    STRINGi9606.ENSP00000266991.

    Structurei

    Secondary structure

    1
    396
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi48 – 525
    Turni57 – 604
    Helixi73 – 764
    Beta strandi85 – 873
    Beta strandi92 – 943
    Helixi95 – 973
    Helixi101 – 11717
    Beta strandi123 – 1275
    Helixi140 – 1434
    Beta strandi146 – 1516
    Helixi156 – 1583
    Helixi159 – 16810
    Beta strandi172 – 1787
    Beta strandi181 – 1855

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2WFQX-ray1.85A39-194[»]
    2WFRX-ray1.95A39-194[»]
    2WG3X-ray2.60A/B40-194[»]
    3N1GX-ray1.90A/B24-189[»]
    3N1QX-ray2.89A/B/E24-189[»]
    ProteinModelPortaliO43323.
    SMRiO43323. Positions 39-189, 199-345.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO43323.

    Family & Domainsi

    Domaini

    The desert hedgehog protein N-product binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.2 Publications

    Sequence similaritiesi

    Belongs to the hedgehog family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG250647.
    HOGENOMiHOG000233428.
    HOVERGENiHBG005480.
    InParanoidiO43323.
    KOiK11990.
    OMAiHSCGPGR.
    OrthoDBiEOG779NZ5.
    PhylomeDBiO43323.
    TreeFamiTF106458.

    Family and domain databases

    Gene3Di2.170.16.10. 1 hit.
    3.30.1380.10. 1 hit.
    InterProiIPR001657. Hedgehog.
    IPR028992. Hedgehog/Intein_dom.
    IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom.
    IPR000320. Hedgehog_signalling_dom.
    IPR001767. Hint_dom.
    IPR003586. Hint_dom_C.
    IPR003587. Hint_dom_N.
    [Graphical view]
    PfamiPF01085. HH_signal. 1 hit.
    PF01079. Hint. 1 hit.
    [Graphical view]
    PIRSFiPIRSF009400. Peptidase_C46. 1 hit.
    PRINTSiPR00632. SONICHHOG.
    SMARTiSM00305. HintC. 1 hit.
    SM00306. HintN. 1 hit.
    [Graphical view]
    SUPFAMiSSF51294. SSF51294. 1 hit.
    SSF55166. SSF55166. 1 hit.

    Sequencei

    Sequence statusi: Complete.

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

    O43323-1 [UniParc]FASTAAdd to Basket

    « Hide

    MALLTNLLPL CCLALLALPA QSCGPGRGPV GRRRYARKQL VPLLYKQFVP    50
    GVPERTLGAS GPAEGRVARG SERFRDLVPN YNPDIIFKDE ENSGADRLMT 100
    ERCKERVNAL AIAVMNMWPG VRLRVTEGWD EDGHHAQDSL HYEGRALDIT 150
    TSDRDRNKYG LLARLAVEAG FDWVYYESRN HVHVSVKADN SLAVRAGGCF 200
    PGNATVRLWS GERKGLRELH RGDWVLAADA SGRVVPTPVL LFLDRDLQRR 250
    ASFVAVETEW PPRKLLLTPW HLVFAARGPA PAPGDFAPVF ARRLRAGDSV 300
    LAPGGDALRP ARVARVAREE AVGVFAPLTA HGTLLVNDVL ASCYAVLESH 350
    QWAHRAFAPL RLLHALGALL PGGAVQPTGM HWYSRLLYRL AEELLG 396
    Length:396
    Mass (Da):43,577
    Last modified:June 1, 1998 - v1
    Checksum:iFCE4FB21972C3AD5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti177 – 1771E → G in AAB03398. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti162 – 1621L → P in GDXYM. 1 Publication
    VAR_054873

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB010994 Genomic DNA. Translation: BAA24866.1.
    BC033507 mRNA. Translation: AAH33507.1.
    U59748 mRNA. Translation: AAB03398.1.
    CCDSiCCDS8779.1.
    PIRiG02735.
    RefSeqiNP_066382.1. NM_021044.2.
    UniGeneiHs.524382.

    Genome annotation databases

    EnsembliENST00000266991; ENSP00000266991; ENSG00000139549.
    GeneIDi50846.
    KEGGihsa:50846.
    UCSCiuc001rtf.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB010994 Genomic DNA. Translation: BAA24866.1 .
    BC033507 mRNA. Translation: AAH33507.1 .
    U59748 mRNA. Translation: AAB03398.1 .
    CCDSi CCDS8779.1.
    PIRi G02735.
    RefSeqi NP_066382.1. NM_021044.2.
    UniGenei Hs.524382.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2WFQ X-ray 1.85 A 39-194 [» ]
    2WFR X-ray 1.95 A 39-194 [» ]
    2WG3 X-ray 2.60 A/B 40-194 [» ]
    3N1G X-ray 1.90 A/B 24-189 [» ]
    3N1Q X-ray 2.89 A/B/E 24-189 [» ]
    ProteinModelPortali O43323.
    SMRi O43323. Positions 39-189, 199-345.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 119151. 1 interaction.
    DIPi DIP-48538N.
    STRINGi 9606.ENSP00000266991.

    Protein family/group databases

    MEROPSi C46.004.

    Proteomic databases

    PaxDbi O43323.
    PRIDEi O43323.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000266991 ; ENSP00000266991 ; ENSG00000139549 .
    GeneIDi 50846.
    KEGGi hsa:50846.
    UCSCi uc001rtf.3. human.

    Organism-specific databases

    CTDi 50846.
    GeneCardsi GC12M049483.
    GeneReviewsi DHH.
    HGNCi HGNC:2865. DHH.
    HPAi CAB034386.
    MIMi 233420. phenotype.
    605423. gene.
    607080. phenotype.
    neXtProti NX_O43323.
    Orphaneti 242. 46,XY complete gonadal dysgenesis.
    168563. 46,XY gonadal dysgenesis - motor and sensory neuropathy.
    PharmGKBi PA27326.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG250647.
    HOGENOMi HOG000233428.
    HOVERGENi HBG005480.
    InParanoidi O43323.
    KOi K11990.
    OMAi HSCGPGR.
    OrthoDBi EOG779NZ5.
    PhylomeDBi O43323.
    TreeFami TF106458.

    Enzyme and pathway databases

    Reactomei REACT_18372. Class B/2 (Secretin family receptors).
    SignaLinki O43323.

    Miscellaneous databases

    EvolutionaryTracei O43323.
    GeneWikii Desert_hedgehog_protein.
    GenomeRNAii 50846.
    NextBioi 53313.
    PROi O43323.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43323.
    Bgeei O43323.
    CleanExi HS_DHH.
    Genevestigatori O43323.

    Family and domain databases

    Gene3Di 2.170.16.10. 1 hit.
    3.30.1380.10. 1 hit.
    InterProi IPR001657. Hedgehog.
    IPR028992. Hedgehog/Intein_dom.
    IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom.
    IPR000320. Hedgehog_signalling_dom.
    IPR001767. Hint_dom.
    IPR003586. Hint_dom_C.
    IPR003587. Hint_dom_N.
    [Graphical view ]
    Pfami PF01085. HH_signal. 1 hit.
    PF01079. Hint. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF009400. Peptidase_C46. 1 hit.
    PRINTSi PR00632. SONICHHOG.
    SMARTi SM00305. HintC. 1 hit.
    SM00306. HintN. 1 hit.
    [Graphical view ]
    SUPFAMi SSF51294. SSF51294. 1 hit.
    SSF55166. SSF55166. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Expression of Sonic hedgehog and its receptor Patched/Smoothened in human cancer cell lines and embryonic organs."
      Tate G., Kishimoto K., Mitsuya T.
      J. Biochem. Mol. Biol. Biophys. 4:27-34(2000)
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    3. "Human desert hedgehog."
      Drummond I.A.
      Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-178.
      Tissue: Kidney.
    4. "A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy."
      Umehara F., Tate G., Itoh K., Yamaguchi N., Douchi T., Mitsuya T., Osame M.
      Am. J. Hum. Genet. 67:1302-1305(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PGD.
    5. "Structural insights into hedgehog ligand sequestration by the human hedgehog-interacting protein HHIP."
      Bishop B., Aricescu A.R., Harlos K., O'Callaghan C.A., Jones E.Y., Siebold C.
      Nat. Struct. Mol. Biol. 16:698-703(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 39-194 IN COMPLEX WITH HHIP AND ZINC IONS, CALCIUM-BINDING, DOMAIN, INTERACTION WITH HHIP.
    6. "All mammalian Hedgehog proteins interact with cell adhesion molecule, down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved manner."
      Kavran J.M., Ward M.D., Oladosu O.O., Mulepati S., Leahy D.J.
      J. Biol. Chem. 285:24584-24590(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 24-189 IN COMPLEXES WITH BOC; CDON; ZINC AND CALCIUM IONS, DOMAIN, INTERACTION WITH BOC AND CDON.
    7. "Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis."
      Canto P., Soederlund D., Reyes E., Mendez J.P.
      J. Clin. Endocrinol. Metab. 89:4480-4483(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT GDXYM PRO-162.
    8. Erratum
      Canto P., Soederlund D., Reyes E., Mendez J.P.
      J. Clin. Endocrinol. Metab. 89:5453-5453(2004)

    Entry informationi

    Entry nameiDHH_HUMAN
    AccessioniPrimary (citable) accession number: O43323
    Secondary accession number(s): Q15794
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: June 1, 1998
    Last modified: October 1, 2014
    This is version 139 of the entry and version 1 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3