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O43323

- DHH_HUMAN

UniProt

O43323 - DHH_HUMAN

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Protein

Desert hedgehog protein

Gene

DHH

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

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. 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
Complete GO annotation...

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 region Source: UniProtKB-KW
  2. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

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

BgeeiO43323.
CleanExiHS_DHH.
ExpressionAtlasiO43323. baseline.
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.
GeneTreeiENSGT00390000001117.
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

        10         20         30         40         50
MALLTNLLPL CCLALLALPA QSCGPGRGPV GRRRYARKQL VPLLYKQFVP
60 70 80 90 100
GVPERTLGAS GPAEGRVARG SERFRDLVPN YNPDIIFKDE ENSGADRLMT
110 120 130 140 150
ERCKERVNAL AIAVMNMWPG VRLRVTEGWD EDGHHAQDSL HYEGRALDIT
160 170 180 190 200
TSDRDRNKYG LLARLAVEAG FDWVYYESRN HVHVSVKADN SLAVRAGGCF
210 220 230 240 250
PGNATVRLWS GERKGLRELH RGDWVLAADA SGRVVPTPVL LFLDRDLQRR
260 270 280 290 300
ASFVAVETEW PPRKLLLTPW HLVFAARGPA PAPGDFAPVF ARRLRAGDSV
310 320 330 340 350
LAPGGDALRP ARVARVAREE AVGVFAPLTA HGTLLVNDVL ASCYAVLESH
360 370 380 390
QWAHRAFAPL RLLHALGALL PGGAVQPTGM HWYSRLLYRL AEELLG
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.
GeneTreei ENSGT00390000001117.
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

Bgeei O43323.
CleanExi HS_DHH.
ExpressionAtlasi O43323. baseline.
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

« Hide 'large scale' publications
  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 29, 2014
This is version 140 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