O43323 (DHH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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. Desert hedgehog protein N-product
2. Desert hedgehog protein C-product

Gene names

Name:

DHH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	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.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 Reference proteome
Gene Ontology (GO)
Biological_process	Leydig cell differentiation Inferred from electronic annotation. Source: Compara cell cycle process Inferred from electronic annotation. Source: Compara cell-cell signaling Inferred from electronic annotation. Source: InterPro male sex determination Inferred from electronic annotation. Source: Compara proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of steroid biosynthetic process Inferred from electronic annotation. Source: Compara spermatid development Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from direct assay PubMed 19561611. Source: UniProtKB peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from direct assay PubMed 19561611. Source: UniProtKB
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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396

Helix Strand Turn

Details...

Beta strand

48 – 52

5

Turn

57 – 60

4

Helix

73 – 76

4

Beta strand

85 – 87

3

Beta strand

92 – 94

3

Helix

95 – 97

3

Helix

101 – 117

17

Beta strand

123 – 127

5

Helix

140 – 143

4

Beta strand

146 – 151

6

Helix

156 – 158

3

Helix

159 – 168

10

Beta strand

172 – 178

7

Beta strand

181 – 185

5

Sequences

	Sequence		Length	Mass (Da)
	O43323 [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] [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]	"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.
[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. NM_021044.2.

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	[»]
3N1G	X-ray	1.90	A/B	24-189	[»]
3N1Q	X-ray	2.89	A/B/E	24-189	[»]

ProteinModelPortal

O43323.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48538N.

STRING

9606.ENSP00000266991.

Protein family/group databases

MEROPS

C46.004.

Proteomic databases

PaxDb

O43323.

PRIDE

O43323.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000266991; ENSP00000266991; ENSG00000139549.

GeneID

50846.

KEGG

hsa:50846.

UCSC

uc001rtf.3. human.

Organism-specific databases

CTD

50846.

GeneCards

GC12M049483.

HGNC

HGNC:2865. DHH.

HPA

CAB034386.

MIM

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

neXtProt

NX_O43323.

Orphanet

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

PharmGKB

PA27326.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG250647.

HOGENOM

HOG000233428.

HOVERGEN

HBG005480.

InParanoid

O43323.

KO

K11990.

OMA

HSCGPGR.

OrthoDB

EOG46WZ8G.

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

Gene3D

3.30.1380.10. 1 hit.

InterPro

IPR001657. Hedgehog.
IPR009045. Hedgehog_sig/DD-Pept_Zn-bd_dom.
IPR000320. Hedgehog_signaling_dom.
IPR001767. Hint_dom.
IPR003586. Hint_dom_C.
IPR003587. Hint_dom_N.
[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]

SUPFAM

SSF55166. Hedgehog_sig_N. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

O43323.

GenomeRNAi

50846.

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:	May 1, 2013
This is version 126 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.