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Protein

Desert hedgehog protein

Gene

DHH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
Metal bindingi90Calcium 1Combined sources2 Publications1
Metal bindingi91Calcium 1Combined sources2 Publications1
Metal bindingi91Calcium 2Combined sources2 Publications1
Metal bindingi96Calcium 1Combined sources2 Publications1
Metal bindingi126Calcium 1; via carbonyl oxygenCombined sources2 Publications1
Metal bindingi127Calcium 1Combined sources2 Publications1
Metal bindingi127Calcium 2Combined sources2 Publications1
Metal bindingi130Calcium 2Combined sources2 Publications1
Metal bindingi132Calcium 2Combined sources2 Publications1
Metal bindingi141ZincCombined sources2 Publications1
Metal bindingi148ZincCombined sources2 Publications1
Metal bindingi183ZincCombined sources2 Publications1
Sitei244Involved in cholesterol transferBy similarity1
Sitei268Involved in auto-cleavageBy similarity1
Sitei271Essential for auto-cleavageBy similarity1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • peptidase activity Source: UniProtKB-KW
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Hydrolase, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139549-MONOMER.
ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362798. Release of Hh-Np from the secreting cell.
R-HSA-5632681. Ligand-receptor interactions.
R-HSA-5632684. Hedgehog 'on' state.
R-HSA-5635838. Activation of SMO.
R-HSA-5658034. HHAT G278V abrogates palmitoylation of Hh-Np.
SignaLinkiO43323.
SIGNORiO43323.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:2865. DHH.

Subcellular locationi

Desert hedgehog protein N-product :
Desert hedgehog protein C-product :

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized 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.
See also OMIM:607080
46,XY sex reversal 7 (SRXY7)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. SRXY7 patients have no functional gonads.
See also OMIM:233420
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054873162L → P in SRXY7. 1 PublicationCorresponds to variant rs111033589dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi50846.
MalaCardsiDHH.
MIMi233420. phenotype.
607080. phenotype.
OpenTargetsiENSG00000139549.
Orphaneti242. 46,XY complete gonadal dysgenesis.
168563. 46,XY gonadal dysgenesis - motor and sensory neuropathy.
PharmGKBiPA27326.

Polymorphism and mutation databases

BioMutaiDHH.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000001324423 – 396Desert hedgehog proteinAdd BLAST374
ChainiPRO_000001324523 – 198Desert hedgehog protein N-productAdd BLAST176
ChainiPRO_0000013246199 – 396Desert hedgehog protein C-productAdd BLAST198

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi23N-palmitoyl cysteineBy similarity1
Lipidationi198Cholesterol glycine esterBy similarity1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei198 – 199Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Lipoprotein, Palmitate

Proteomic databases

PaxDbiO43323.
PeptideAtlasiO43323.
PRIDEiO43323.

PTM databases

PhosphoSitePlusiO43323.

Expressioni

Gene expression databases

BgeeiENSG00000139549.
CleanExiHS_DHH.
GenevisibleiO43323. HS.

Organism-specific databases

HPAiCAB034386.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi119151. 6 interactors.
DIPiDIP-48538N.
IntActiO43323. 1 interactor.
STRINGi9606.ENSP00000266991.

Structurei

Secondary structure

1396
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi48 – 52Combined sources5
Turni57 – 60Combined sources4
Helixi73 – 76Combined sources4
Beta strandi85 – 87Combined sources3
Beta strandi92 – 94Combined sources3
Helixi95 – 97Combined sources3
Helixi101 – 117Combined sources17
Beta strandi123 – 127Combined sources5
Helixi140 – 143Combined sources4
Beta strandi146 – 151Combined sources6
Helixi156 – 158Combined sources3
Helixi159 – 168Combined sources10
Beta strandi172 – 178Combined sources7
Beta strandi181 – 185Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
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

eggNOGiKOG3638. Eukaryota.
ENOG410XQA3. LUCA.
GeneTreeiENSGT00390000001117.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiO43323.
KOiK11990.
OMAiPSMPERT.
OrthoDBiEOG091G0N90.
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)DescriptionActionsGraphical viewLength
Sequence conflicti177E → G in AAB03398 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054873162L → P in SRXY7. 1 PublicationCorresponds to variant rs111033589dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_021044.3.
UniGeneiHs.524382.
Hs.533776.

Genome annotation databases

EnsembliENST00000266991; ENSP00000266991; ENSG00000139549.
GeneIDi50846.
KEGGihsa:50846.
UCSCiuc001rtf.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_021044.3.
UniGeneiHs.524382.
Hs.533776.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119151. 6 interactors.
DIPiDIP-48538N.
IntActiO43323. 1 interactor.
STRINGi9606.ENSP00000266991.

Protein family/group databases

MEROPSiC46.004.

PTM databases

PhosphoSitePlusiO43323.

Polymorphism and mutation databases

BioMutaiDHH.

Proteomic databases

PaxDbiO43323.
PeptideAtlasiO43323.
PRIDEiO43323.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000266991; ENSP00000266991; ENSG00000139549.
GeneIDi50846.
KEGGihsa:50846.
UCSCiuc001rtf.4. human.

Organism-specific databases

CTDi50846.
DisGeNETi50846.
GeneCardsiDHH.
GeneReviewsiDHH.
HGNCiHGNC:2865. DHH.
HPAiCAB034386.
MalaCardsiDHH.
MIMi233420. phenotype.
605423. gene.
607080. phenotype.
neXtProtiNX_O43323.
OpenTargetsiENSG00000139549.
Orphaneti242. 46,XY complete gonadal dysgenesis.
168563. 46,XY gonadal dysgenesis - motor and sensory neuropathy.
PharmGKBiPA27326.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3638. Eukaryota.
ENOG410XQA3. LUCA.
GeneTreeiENSGT00390000001117.
HOGENOMiHOG000233428.
HOVERGENiHBG005480.
InParanoidiO43323.
KOiK11990.
OMAiPSMPERT.
OrthoDBiEOG091G0N90.
PhylomeDBiO43323.
TreeFamiTF106458.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139549-MONOMER.
ReactomeiR-HSA-373080. Class B/2 (Secretin family receptors).
R-HSA-5358346. Hedgehog ligand biogenesis.
R-HSA-5362798. Release of Hh-Np from the secreting cell.
R-HSA-5632681. Ligand-receptor interactions.
R-HSA-5632684. Hedgehog 'on' state.
R-HSA-5635838. Activation of SMO.
R-HSA-5658034. HHAT G278V abrogates palmitoylation of Hh-Np.
SignaLinkiO43323.
SIGNORiO43323.

Miscellaneous databases

EvolutionaryTraceiO43323.
GeneWikiiDesert_hedgehog_protein.
GenomeRNAii50846.
PROiO43323.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139549.
CleanExiHS_DHH.
GenevisibleiO43323. HS.

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.
ProtoNetiSearch...

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: November 30, 2016
This is version 161 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

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.