Reviewed, UniProtKB/Swiss-Prot O43323 (DHH_HUMAN)

Names and origin

Protein names

Recommended name:
    Desert hedgehog protein
      Short name=DHH
Alternative name(s):
    HHG-3
Cleaved into the following 2 chains:
    1- Recommended name:
            Desert hedgehog protein N-product
    2- Recommended name:
            Desert hedgehog protein C-product

Gene names

Name:

DHH

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	396 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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: Secreted › extracellular space By similarity. Note: The C-terminal peptide diffuses from the cell By similarity.
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	Defects in DHH may be the cause of partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:607080]. PGD is 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. Ref.4 Defects in DHH may be the cause of complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:233420]; also known as male-limited gonadal dysgenesis 46,XY. GDXYM is a 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. Ref.5
Sequence similarities	Belongs to the hedgehog family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Disease	Disease mutation
Domain	Signal
Molecular function	Developmental protein Hydrolase Protease
PTM	Autocatalytic cleavage Lipoprotein Palmitate
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell-cell signaling Inferred from electronic annotation. Source: InterPro proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Chain

23 – 396

374

Desert hedgehog protein

PRO_0000013244

Chain

23 – 198

176

Desert hedgehog protein N-product

PRO_0000013245

Chain

199 – 396

198

Desert hedgehog protein C-product

PRO_0000013246

Sites

Site

198 – 199

2

Cleavage; by autolysis By similarity

Site

244

1

Involved in cholesterol transfer By similarity

Site

268

1

Involved in auto-cleavage By similarity

Site

271

1

Essential for auto-cleavage By similarity

Amino acid modifications

Lipidation

23

1

N-palmitoyl cysteine By similarity

Lipidation

198

1

Cholesterol glycine ester By similarity

Natural variations

Natural variant

162

1

L → P in GDXYM. Ref.5

VAR_054873

Experimental info

Sequence conflict

177

1

E → G in AAB03398. Ref.3

Secondary structure

1

.

.

.

.

.

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.

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.

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.

.

396

Helix Strand Turn

Details...

Helix

73 – 76

4

Beta strand

85 – 87

3

Helix

101 – 117

17

Beta strand

123 – 127

5

Helix

140 – 142

3

Beta strand

146 – 151

6

Helix

156 – 158

3

Helix

162 – 168

7

Beta strand

173 – 178

6

Beta strand

181 – 185

5

Sequences

	Sequence		Length	Mass (Da)
	O43323-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: FCE4FB21972C3AD5	FASTA	396	43,577
	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

References

	« Hide 'large scale' referencesShow '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: 15489334] [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: 11017805] [Abstract] Cited for: INVOLVEMENT IN PGD.
[5]	"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: 15356051] [Abstract] Cited for: VARIANT GDXYM PRO-162.
[6]	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.

IPI

IPI00011978.

PIR

G02735.

RefSeq

NP_066382.1.

UniGene

Hs.524382

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

SMR

O43323. Positions 199-345.

ModBase

Search...

Protein-protein interaction databases

STRING

O43323.

Protein family/group databases

MEROPS

C46.004.

Proteomic databases

PRIDE

O43323.

Genome annotation databases

Ensembl

ENST00000266991; ENSP00000266991; ENSG00000139549; Homo sapiens. [Genome view]

GeneID

50846.

KEGG

hsa:50846.

UCSC

uc001rtf.1. human.

Organism-specific databases

CTD

50846.

GeneCards

GC12M047769.

H-InvDB

HIX0026385.

HGNC

HGNC:2865. DHH.

MIM

233420. phenotype.
605423. gene.
607080. phenotype.

Orphanet

168563. 46,XY gonadal dysgenesis - motor and sensory neuropathy.
242. Gonadal dysgenesis, XY female type.
1770. Gonadal dysgenesis, XY type - associated anomalies.

PharmGKB

PA27326.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08414.

HOGENOM

HBG403179.

HOVERGEN

O43323.

InParanoid

O43323.

OMA

YKQFVPS.

OrthoDB

EOG92JRBP.

PhylomeDB

O43323.

Enzyme and pathway databases

Pathway_Interaction_DB

hedgehog_2pathway. Signaling events mediated by the Hedgehog family.

Gene expression databases

ArrayExpress

O43323.

Bgee

O43323.

CleanEx

HS_DHH.

Genevestigator

O43323.

GermOnline

ENSG00000139549. Homo sapiens.

Family and domain databases

InterPro

IPR009045. Hedgehog/DD-pept_Zn-bd.
IPR003586. Hedgehog_hint_C.
IPR003587. Hedgehog_hint_N.
IPR000320. Hedgehog_signaling_dom.
IPR001657. Peptidase_C46.
IPR001767. Peptidase_C46_hint.
[Graphical view]

Pfam

PF01085. HH_signal. 1 hit.
PF01079. Hint. 1 hit.
[Graphical view]

PIRSF

PIRSF009400. Peptidase_C46. 1 hit.

PRINTS

PR00632. SONICHHOG.

SMART

SM00305. HintC. 1 hit.
SM00306. HintN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

53313.

SOURCE

Search...

Entry information

Entry name

DHH_HUMAN

Accession

Primary (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:	February 9, 2010
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.