DHH
entrez
50846
canonical
uniprot
O43323
canonical
ensembl
ENSG00000139549
resolver
ensp
ENSP00000497483
resolver
enst
ENST00000649637
resolver
genesymbol
DHH
resolver
hgnc
HGNC:2865
resolver
uniprot
Q15794
resolver
uniprot_entry
DHH_HUMAN
resolver
uniprot_sec
Q15794
resolver
amino_acid_sequence
MALLTNLLPLCCLALLALPAQSCGPGRGPVGRRRYARKQLVPLLYKQFVPGVPERTLGASGPAEGRVARGSERFRDLVPNYNPDIIFKDEENSGADRLMTERCKERVNALAIAVMNMWPGVRLRVTEGWDEDGHHAQDSLHYEGRALDITTSDRDRNKYGLLARLAVEAGFDWVYYESRNHVHVSVKADNSLAVRAGGCFPGNATVRLWSGERKGLRELHRGDWVLAADASGRVVPTPVLLFLDRDLQRRASFVAVETEWPPRKLLLTPWHLVFAARGPAPAPGDFAPVFARRLRAGDSVLAPGGDALRPARVARVAREEAVGVFAPLTAHGTLLVNDVLASCYAVLESHQWAHRAFAPLRLLHALGALLPGGAVQPTGMHWYSRLLYRLAEELLG
uniprot
proteins
disease_involvement
DISEASE: 46,XY gonadal dysgenesis with minifascicular neuropathy (GDMN) [MIM:607080]: An autosomal recessive disorder characterized by gonadal dysgenesis associated with polyneuropathy. Genital anomalies include 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. {ECO:0000269|PubMed:11017805, ECO:0000269|PubMed:25927242, ECO:0000269|PubMed:28589169, ECO:0000269|PubMed:28708305, ECO:0000269|PubMed:29471294, ECO:0000269|PubMed:30298535}. Note=The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: 46,XY sex reversal 7 (SRXY7) [MIM:233420]: A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. SRXY7 patients have no functional gonads. {ECO:0000269|PubMed:15356051}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.-.-
uniprot
proteins
function
FUNCTION: [Desert hedgehog protein]: Precursor of desert hedgehog, a morphogen that activates the smoothened signaling pathway, and which is essential for a variety of patterning events during development (By similarity). The C-terminal part of the precursor displays an autoproteolysis and a cholesterol transferase activity, resulting (1) in the cleavage of the full-length protein into two parts, desert hedgehog protein N-product and C-product and (2) covalent attachment of a cholesterol moiety to the C-terminus of the newly generated N-product (DHH-N) (By similarity). Both autoproteolysis and a cholesterol transferase activities occur in the endoplasmic reticulum (By similarity). Following additional lipidation, DHH-N acts as a morphogen, while the C-product is degraded in the endoplasmic reticulum (By similarity). {ECO:0000250|UniProtKB:Q62226}.; FUNCTION: [Desert hedgehog protein N-product]: The dually lipidated desert hedgehog protein N-product is a morphogen that activates the smoothened signaling pathway, and which is essential for a variety of patterning events during development (By similarity). Acts by binding to the patched receptor (PTCH1 or PTCH2), relieving smoothened (SMO) inhibition by patched, activating the smoothened signaling pathway and transcription of target genes (PubMed:11472839, PubMed:33063110). In the absence of DHH, patched represses the constitutive signaling activity of SMO (By similarity). DHH plays a key role in male gonad development (spermatogenesis) and the formation of Schwann cells (By similarity). Required for normal testis development and spermatogenesis, namely for the formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules (By similarity). In Schwann cells, controls the development of the peripheral nerve sheath and the transition of mesenchymal cells to form the epithelium-like structure of the perineurial tube (By similarity). May induce motor neurons in lateral neural tube and may have a polarizing activity (PubMed:11472839). Involved in tissue regeneration: secreted from epithelial neuroendocrine cells and elicits a regenerative response from mesenchymal cells (By similarity). Functions in cell-cell mediated juxtacrine signaling (PubMed:24342078). Activates primary cilia signaling on neighboring valve interstitial cells through a paracrine mechanism (By similarity). Promotes endothelium integrity (PubMed:33063110). {ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q61488, ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:11472839, ECO:0000269|PubMed:24342078, ECO:0000269|PubMed:33063110}.
uniprot
proteins
mass_dalton
43577
uniprot
proteins
mutagenesis
MUTAGEN 23; /note="C->A: Loss of palmitoylation."; /evidence="ECO:0000269|PubMed:24784881
uniprot
proteins
post_translational_modification
PTM: [Desert hedgehog protein]: The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (PubMed:24342078, PubMed:30298535). 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 (DHH-N) (By similarity). DHH-N is the active species in both local and long-range signaling, whereas the C-product is degraded in the endoplasmic reticulum (By similarity). {ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:24342078, ECO:0000269|PubMed:30298535}.; PTM: [Desert hedgehog protein N-product]: Dually lipidated: a cholesterol moiety is attached to its C-terminus following cleavage (By similarity). N-palmitoylated by HHAT following cholesterylation; palmitoylation is required for desert hedgehog protein N-product multimerization and full activity (PubMed:24784881). {ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:24784881}.
uniprot
proteins
protein_family
Hedgehog family
uniprot
proteins
pubmed
11017805
uniprot
proteins
pubmed
11472839
uniprot
proteins
pubmed
15356051
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19561611
uniprot
proteins
pubmed
20519495
uniprot
proteins
pubmed
24342078
uniprot
proteins
pubmed
24784881
uniprot
proteins
pubmed
25927242
uniprot
proteins
pubmed
28589169
uniprot
proteins
pubmed
28708305
uniprot
proteins
pubmed
29471294
uniprot
proteins
pubmed
30298535
uniprot
proteins
pubmed
33063110
uniprot
proteins
sequence_length
396
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Desert hedgehog protein]: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q15465}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q15465}. Note=Co-localizes with HHAT in the ER and Golgi membrane. {ECO:0000250|UniProtKB:Q15465}.; SUBCELLULAR LOCATION: [Desert hedgehog protein N-product]: Secreted {ECO:0000269|PubMed:33063110}. Cell membrane {ECO:0000269|PubMed:24342078}; Lipid-anchor {ECO:0000250|UniProtKB:Q62226}.
uniprot
proteins