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O43323 (DHH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Desert hedgehog protein

Short name=DHH
Alternative name(s):
HHG-3
Gene names
Name:DHH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length396 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

Interacts with BOC and CDON. Interacts with HHIP. Ref.5 Ref.6

Subcellular location

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

Desert hedgehog protein C-product: Secretedextracellular space By similarity. Note: The C-terminal peptide diffuses from the cell By similarity.

Domain

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. Ref.5 Ref.6

Post-translational modification

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.

Involvement in disease

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.
Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.4

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.
Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the hedgehog family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Chain23 – 396374Desert hedgehog protein
PRO_0000013244
Chain23 – 198176Desert hedgehog protein N-product
PRO_0000013245
Chain199 – 396198Desert hedgehog protein C-product
PRO_0000013246

Sites

Metal binding901Calcium 1
Metal binding911Calcium 1
Metal binding911Calcium 2
Metal binding961Calcium 1
Metal binding1261Calcium 1; via carbonyl oxygen
Metal binding1271Calcium 1
Metal binding1271Calcium 2
Metal binding1301Calcium 2
Metal binding1321Calcium 2
Metal binding1411Zinc
Metal binding1481Zinc
Metal binding1831Zinc
Site198 – 1992Cleavage; by autolysis By similarity
Site2441Involved in cholesterol transfer By similarity
Site2681Involved in auto-cleavage By similarity
Site2711Essential for auto-cleavage By similarity

Amino acid modifications

Lipidation231N-palmitoyl cysteine By similarity
Lipidation1981Cholesterol glycine ester By similarity

Natural variations

Natural variant1621L → P in GDXYM. Ref.7
VAR_054873

Experimental info

Sequence conflict1771E → G in AAB03398. Ref.3

Secondary structure

........................... 396
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43323 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: FCE4FB21972C3AD5

FASTA39643,577
        10         20         30         40         50         60 
MALLTNLLPL CCLALLALPA QSCGPGRGPV GRRRYARKQL VPLLYKQFVP GVPERTLGAS 

        70         80         90        100        110        120 
GPAEGRVARG SERFRDLVPN YNPDIIFKDE ENSGADRLMT ERCKERVNAL AIAVMNMWPG 

       130        140        150        160        170        180 
VRLRVTEGWD EDGHHAQDSL HYEGRALDIT TSDRDRNKYG LLARLAVEAG FDWVYYESRN 

       190        200        210        220        230        240 
HVHVSVKADN SLAVRAGGCF PGNATVRLWS GERKGLRELH RGDWVLAADA SGRVVPTPVL 

       250        260        270        280        290        300 
LFLDRDLQRR ASFVAVETEW PPRKLLLTPW HLVFAARGPA PAPGDFAPVF ARRLRAGDSV 

       310        320        330        340        350        360 
LAPGGDALRP ARVARVAREE AVGVFAPLTA HGTLLVNDVL ASCYAVLESH QWAHRAFAPL 

       370        380        390 
RLLHALGALL PGGAVQPTGM HWYSRLLYRL AEELLG 

« Hide

References

« Hide 'large scale' references
[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)
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB010994 Genomic DNA. Translation: BAA24866.1.
BC033507 mRNA. Translation: AAH33507.1.
U59748 mRNA. Translation: AAB03398.1.
PIRG02735.
RefSeqNP_066382.1. NM_021044.2.
UniGeneHs.524382.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalO43323.
SMRO43323. Positions 39-189, 199-345.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119151. 1 interaction.
DIPDIP-48538N.
STRING9606.ENSP00000266991.

Protein family/group databases

MEROPSC46.004.

Proteomic databases

PaxDbO43323.
PRIDEO43323.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000266991; ENSP00000266991; ENSG00000139549.
GeneID50846.
KEGGhsa:50846.
UCSCuc001rtf.3. human.

Organism-specific databases

CTD50846.
GeneCardsGC12M049483.
HGNCHGNC:2865. DHH.
HPACAB034386.
MIM233420. phenotype.
605423. gene.
607080. phenotype.
neXtProtNX_O43323.
Orphanet242. 46,XY complete gonadal dysgenesis.
168563. 46,XY gonadal dysgenesis - motor and sensory neuropathy.
PharmGKBPA27326.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG250647.
HOGENOMHOG000233428.
HOVERGENHBG005480.
InParanoidO43323.
KOK11990.
OMAHSCGPGR.
OrthoDBEOG779NZ5.
PhylomeDBO43323.
TreeFamTF106458.

Enzyme and pathway databases

SignaLinkO43323.

Gene expression databases

ArrayExpressO43323.
BgeeO43323.
CleanExHS_DHH.
GenevestigatorO43323.

Family and domain databases

Gene3D3.30.1380.10. 1 hit.
InterProIPR001657. Hedgehog.
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]
PfamPF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view]
PIRSFPIRSF009400. Peptidase_C46. 1 hit.
PRINTSPR00632. SONICHHOG.
SMARTSM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view]
SUPFAMSSF55166. SSF55166. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceO43323.
GeneWikiDesert_hedgehog_protein.
GenomeRNAi50846.
NextBio53313.
PROO43323.
SOURCESearch...

Entry information

Entry nameDHH_HUMAN
AccessionPrimary (citable) accession number: O43323
Secondary accession number(s): Q15794
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: March 19, 2014
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM