Sonic hedgehog

SHH
Tilgængelige strukturer
PDB	Ortologsøgning: PDBe RCSB
Liste over PDB-idkoder
	3HO5, 3M1N, 3MXW
Identifikatorer
Aliaser	SHH, HHG1, HLP3, HPE3, MCOPCB5, SMMCI, TPT, TPTPS, sonic hedgehog, Sonic hedgehog, ShhNC, sonic hedgehog signaling molecule
External IDs	OMIM: 600725 MGI: 98297 HomoloGene: 30961 GeneCards: SHH
Genetisk-relaterede sygdomme
	holoprosencephaly 3, Laurin-Sandrow syndrome
Genontologi
Molekylær funktion	• calcium ion binding; • metal-ion-binding; • patched binding; • GO:0070122 peptidase activity; • zinc ion binding; • laminin-1 binding; • glycosaminoglycan binding; • morphogen activity; • hydrolase activity; • GO:0001948, GO:0016582 proteinbinding; • endopeptidase activity;
Cellulær komponent	• cytosol; • endoplasmic reticulum lumen; • membran; • celleoverflade; • membrane raft; • cellemembran; • ekstracellulære rum; • ekstracellulære region; • GO:0005578 ekstracellulær matrix;
Biologisk proces	• positive regulation of skeletal muscle cell proliferation; • pattern specification process; • myotube differentiation; • mesenchymal cell proliferation; • male genitalia development; • bud outgrowth involved in lung branching; • limb bud formation; • T cell differentiation in thymus; • embryonic pattern specification; • positive regulation of skeletal muscle tissue development; • positive regulation of immature T cell proliferation in thymus; • positive regulation of kidney smooth muscle cell differentiation; • negative regulation of Wnt signaling pathway; • anatomical structure formation involved in morphogenesis; • ectoderm development; • hindgut morphogenesis; • spinal cord dorsal/ventral patterning; • GO:0007364, GO:0007361, GO:0007358 formation of anatomical boundary; • oligodendrocyte differentiation; • trachea development; • prostate gland development; • negative regulation of transcription elongation from RNA polymerase II promoter; • limb development; • vasculogenesis; • primary prostatic bud elongation; • heart looping; • telencephalon regionalization; • odontogenesis of dentin-containing tooth; • positive regulation of mesenchymal cell proliferation; • angiogenesis; • positive regulation of epithelial cell proliferation involved in prostate gland development; • positive regulation of striated muscle cell differentiation; • negative regulation of proteasomal ubiquitin-dependent protein catabolic process; • embryonic digestive tract morphogenesis; • apoptotic signaling pathway; • inner ear development; • hair follicle morphogenesis; • cell population proliferation; • metanephros development; • lung epithelium development; • negative regulation of canonical Wnt signaling pathway; • regulation of proteolysis; • branching involved in salivary gland morphogenesis; • negative regulation of mesenchymal cell apoptotic process; • positive regulation of neuroblast proliferation; • dopaminergic neuron differentiation; • intermediate filament organization; • renal system development; • cell fate commitment; • GO:0009373 regulation of transcription, DNA-templated; • positive regulation of smoothened signaling pathway; • androgen metabolic process; • kidney development; • lung development; • GO:1903363 negative regulation of protein catabolic process; • thymus development; • embryonic organ development; • negative regulation of cell differentiation; • negative regulation of dopaminergic neuron differentiation; • embryonic digit morphogenesis; • negative regulation of alpha-beta T cell differentiation; • positive regulation of sclerotome development; • epithelial-mesenchymal cell signaling; • negative regulation of gene expression; • lymphoid progenitor cell differentiation; • negative thymic T cell selection; • GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated; • positive regulation of Wnt signaling pathway; • ventral midline development; • centralnervesystemsudvikling; • hjertets udvikling; • branching involved in ureteric bud morphogenesis; • negative regulation of T cell proliferation; • embryonic limb morphogenesis; • positive regulation of cell differentiation; • branching involved in prostate gland morphogenesis; • positive regulation of mesenchymal cell proliferation involved in ureter development; • establishment of cell polarity; • branching involved in blood vessel morphogenesis; • positive regulation of cerebellar granule cell precursor proliferation; • neuroblast proliferation; • pancreas development; • positive regulation of protein import into nucleus; • smoothened signaling pathway; • oligodendrocyte development; • camera-type eye development; • spinal cord motor neuron differentiation; • positive regulation of alpha-beta T cell differentiation; • digestive tract morphogenesis; • hair follicle development; • positive regulation of oligodendrocyte differentiation; • roof of mouth development; • left lung development; • striated muscle tissue development; • positive regulation of T cell differentiation in thymus; • cellular response to lithium ion; • embryonic foregut morphogenesis; • GO:1903374 anatomical structure development; • thalamus development; • stem cell development; • smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation; • cell fate specification; • negative regulation of apoptotic process; • GO:1901227 negative regulation of transcription by RNA polymerase II; • regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry; • proteolyse; • embryonic skeletal system development; • regulation of protein localization to nucleus; • odontogenesis; • respiratory tube development; • regulation of prostatic bud formation; • thyroid gland development; • negative regulation of cell migration; • developmental growth; • right lung development; • determination of left/right asymmetry in lateral mesoderm; • positive thymic T cell selection; • mesenchymal smoothened signaling pathway involved in prostate gland development; • canonical Wnt signaling pathway; • genudtryksregulering; • osteoblast development; • negative regulation of cholesterol efflux; • dorsal/ventral neural tube patterning; • regulation of epithelial cell proliferation involved in prostate gland development; • epithelial-mesenchymal signaling involved in prostate gland development; • dorsal/ventral pattern formation; • branching morphogenesis of an epithelial tube; • lung lobe morphogenesis; • embryonic forelimb morphogenesis; • midbrain development; • skin development; • regulation of odontogenesis; • regulation of mesenchymal cell proliferation involved in prostate gland development; • mesenchymal cell proliferation involved in lung development; • positive regulation of hh _target transcription factor activity; • prostate epithelial cord elongation; • metanephric mesenchymal cell proliferation involved in metanephros development; • Endocytose; • lung morphogenesis; • cell development; • trachea morphogenesis; • epithelial cell proliferation involved in salivary gland morphogenesis; • cell-cell signaling; • salivary gland cavitation; • hindbrain development; • koagulation; • negative regulation of kidney smooth muscle cell differentiation; • somite development; • cerebellar granule cell precursor proliferation; • axon guidance; • negative regulation of ureter smooth muscle cell differentiation; • positive regulation of ureter smooth muscle cell differentiation; • multicellular organism development; • animal organ formation; • intein-mediated protein splicing; • determination of left/right symmetry; • vasculature development; • GO:1901313 positive regulation of gene expression; • regulation of cell population proliferation; • embryonic morphogenesis; • neural crest cell migration; • polarity specification of anterior/posterior axis; • positive regulation of cell population proliferation; • artery development; • protein localization to nucleus; • Bergmann glial cell differentiation; • forhjerneudvikling; • neuron fate commitment; • CD4-positive or CD8-positive, alpha-beta T cell lineage commitment; • striated muscle cell differentiation; • myoblast differentiation; • lung-associated mesenchyme development; • epithelial tube branching involved in lung morphogenesis; • positive regulation of cell division; • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II; • anterior/posterior pattern specification; • embryonic hindlimb morphogenesis; • forebrain regionalization; • cell proliferation in external granule layer; • tracheoesophageal septum formation; • regulation of signaling receptor activity;
	Sources:Amigo / QuickGO
RNA-udtryksmønster
	Flere henvisninger til udtrykdata
Ortologer
	6469
	20423
	ENSG00000164690
	ENSMUSG00000002633
	Q15465
	Q62226
	NM_000193; NM_001310462
	NM_009170
	NP_000184; NP_001297391
	NP_033196
	Wikidata
Vis/Rediger Menneske	Vis/Rediger Mus

For computerspilsfiguren, se Sonic the Hedgehog

Sonic hedgehog eller SHH er et protein som i mennesker er kodet for af genet SHH ("sonic hedgehog").^[4] Både genet og proteinet findes også med den alternative notering "Shh".

Sonic hedgehog (SHH) indgår i pattedyrs signaltransduktion. Det er et af tre membranproteiner i familien “hedgehog” - de to andre er Desert hedgehog (DHH) og Indian hedgehog (IHH). SHH er den bedst studerede del af hedgehog-signalvejen. Den spiller en vigtig rolle i regulering af hvirveldyrs organdannelse, såsom vækst af ekstremiteter på lemmer og organiseringen af hjernen. Sonic hedgehog er et af de bedste eksempeler på et molekyle der diffunderer så der dannes en koncentrationsgradient med forskellige effekter på celler i det udviklende embryo afhængigt af koncentrationen. SHH forbliver vigtig i voksne, da det også kontrollerer celledelingen af voksne stamceller og har implikationer for udvikling af nogle typer cancer.

Opdagelse og navngivning

Genet for Hedgehog (som betyder pindsvin på dansk) blev først identificeret i frugtfluen Drosophila melanogaster i en serie af klassiske mutationsundersøgelser, nærmere bestemt genetiske screeninger, udført af Christiane Nüsslein-Volhard og Eric Wieschaus, som blev publiceret i 1980.^[5]. Disse genetiske undersøgelser gav dem Nobelprisen i fysiologi eller medicin i 1995 sammen med udviklingsgenetikeren Edward B. Lewis, der identificerede generne, der kontrollerer segmentationsmønstre, som kan observeres i Drosophila-embryoer. Embryoet af mutantfænotypen, der har mistet funktionen, og som designeres hh, er dækket af små stikkende projektioner, der minder om pindene på et pindsvin.

Undersøgelser er rettet mod at finde et ækvivalent gen til hedgehog i hvirveldyr af Philip Ingham, Andrew P. McMahon, and Clifford Tabin, som fandt tre homologe gener.^[6]^[7]^[8]^[9] To af disse, desert hedgehog og Indian hedgehog, blev navngivet efter arter af pindsvin, mens sonic hedgehog blev navngivet efter SEGA's videospilskarakter Sonic the Hedgehog.^[10]^[11] Navnet blev givet af Robert Riddle, som var postdoc i Tabins laboratorium, efter han så en tegneserie med Sonic, som hans datter havde købt i England.^[12]^[13]

Kontroverser omkring navngivning

Dette gen er associeret med en svær tilstand kaldet holoprosencephali, hvilket resulterer i svære hjerne-, kranie- og ansigtsdefekter. Dette har medført at klinikker og forskere har kritiseret navnet for at være upassende. Det er ikke en humoristisk situation, hvis patienter eller forældre til patienter med en alvorlig sygdom skal forklares, at de eller deres barn har en mutation i deres sonic hedgehog.^[12]^[14]^[15]

Se også

Pikachurin, et retinalt protein opkaldt efter Pikachu

Wikimedia Commons har flere filer relateret til Sonic hedgehog

Referencer

^ "Sygdomme, der er genetisk associerede med SHH vis/rediger henvisninger på wikidata".
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ Marigo V, Roberts DJ, Lee SM, Tsukurov O, Levi T, Gastier JM, Epstein DJ, Gilbert DJ, Copeland NG, Seidman CE (juli 1995). "Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog". Genomics. 28 (1): 44-51. doi:10.1006/geno.1995.1104. PMID 7590746. {{cite journal}}: |url-access= requires |url= (hjælp)
^ Nüsslein-Volhard C, Wieschaus E (oktober 1980). "Mutations affecting segment number and polarity in Drosophila". Nature. 287 (5785): 795-801. doi:10.1038/287795a0. PMID 6776413. {{cite journal}}: |url-access= requires |url= (hjælp)
^ Krauss S, Concordet JP, Ingham PW (december 1993). "A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos". Cell. 75 (7): 1431-44. doi:10.1016/0092-8674(93)90628-4. PMID 8269519. {{cite journal}}: |url-access= requires |url= (hjælp)
^ Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP (december 1993). "Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity". Cell. 75 (7): 1417-30. doi:10.1016/0092-8674(93)90627-3. PMID 7916661.
^ Riddle RD, Johnson RL, Laufer E, Tabin C (1993). "Sonic hedgehog mediates the polarizing activity of the ZPA". Cell. 75 (7): 1401-16. doi:10.1016/0092-8674(93)90626-2. PMID 8269518.
^ Angier N (1994-01-11). "Biologists Find Key Genes That Shape Patterning of Embryos". Science. New York Times.
^ Anwood R (2007-09-06). Emus Can't Walk Backwards. Ebury Press. s. 113-114. ISBN 978-0-09-192151-4.
^ Tom Simonite (2005-12-15). "Pokémon blocks gene name". Vol. 438, no. 897. Nature. doi:10.1038/438897a. Hentet 2013-05-23.
^ ^a ^b "A Gene Named Sonic". The New York Times. 1994-01-11.
^ Annalise Keen & Cliff Tabin (12. april 2004). "Cliff Tabin: Super Sonic An Interview". The Weekly Murmur. Arkiveret fra originalen 10. november 2005. Hentet 27. januar 2018.
^ Maclean K (januar 2006). "Humour of gene names lost in translation to patients". Nature. 439 (7074): 266. doi:10.1038/439266d. PMID 16421543.
^ Cohen MM (juli 2006). "Problems in the naming of genes". Am. J. Med. Genet. A. 140 (13): 1483-4. doi:10.1002/ajmg.a.31264. PMID 16718675.

Yderligere læsning

Dorus S, Anderson JR, Vallender EJ, Gilbert SL, Zhang L, Chemnick LG, Ryder OA, Li W, Lahn BT (2006). "Sonic Hedgehog, a key development gene, experienced intensified molecular evolution in primates". Human Molecular Genetics. 15 (13): 2031-7. doi:10.1093/hmg/ddl123. PMID 16687440.
Gilbert, Scott F. (2000). Developmental biology (6th udgave). Sunderland, Mass: Sinauer Associates. ISBN 0-87893-243-7.
Kim J, Kim P, Hui CC (2001). "The VACTERL association: lessons from the Sonic hedgehog pathway". Clinical Genetics. 59 (5): 306-15. doi:10.1034/j.1399-0004.2001.590503.x. PMID 11359461.
Morton JP, Lewis BC (2007). "SHH signaling and pancreatic cancer: implications for therapy?". Cell Cycle. 6 (13): 1553-7. doi:10.4161/cc.6.13.4467. PMID 17611415.
Mullor JL, Sánchez P, Ruiz i Altaba A (2003). "Pathways and consequences: Hedgehog signaling in human disease". Trends Cell Biol. 12 (12): 562-9. doi:10.1016/S0962-8924(02)02405-4. PMID 12495844.
Nanni L, Ming JE, Du Y, Hall RK, Aldred M, Bankier A, Muenke M (2001). "SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature". American Journal of Medical Genetics. 102 (1): 1-10. doi:10.1002/1096-8628(20010722)102:13.0.CO;2-U. PMID 11471164.
Williams JA (2006). "Hedgehog and spinal cord injury". Expert Opinion on Therapeutic _targets. 9 (6): 1137-45. doi:10.1517/14728222.9.6.1137. PMID 16300466.

[1] "Sygdomme, der er genetisk associerede med SHH vis/rediger henvisninger på wikidata".

[2] "Human PubMed Reference:".

[3] "Mouse PubMed Reference:".

[pmid7590746-4] Marigo V, Roberts DJ, Lee SM, Tsukurov O, Levi T, Gastier JM, Epstein DJ, Gilbert DJ, Copeland NG, Seidman CE (juli 1995). "Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog". Genomics. 28 (1): 44-51. doi:10.1006/geno.1995.1104. PMID 7590746. {{cite journal}}: |url-access= requires |url= (hjælp)

[pmid6776413-5] Nüsslein-Volhard C, Wieschaus E (oktober 1980). "Mutations affecting segment number and polarity in Drosophila". Nature. 287 (5785): 795-801. doi:10.1038/287795a0. PMID 6776413. {{cite journal}}: |url-access= requires |url= (hjælp)

[pmid8269519-6] Krauss S, Concordet JP, Ingham PW (december 1993). "A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos". Cell. 75 (7): 1431-44. doi:10.1016/0092-8674(93)90628-4. PMID 8269519. {{cite journal}}: |url-access= requires |url= (hjælp)

[pmid7916661-7] Echelard Y, Epstein DJ, St-Jacques B, Shen L, Mohler J, McMahon JA, McMahon AP (december 1993). "Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity". Cell. 75 (7): 1417-30. doi:10.1016/0092-8674(93)90627-3. PMID 7916661.

[pmid8269518-8] Riddle RD, Johnson RL, Laufer E, Tabin C (1993). "Sonic hedgehog mediates the polarizing activity of the ZPA". Cell. 75 (7): 1401-16. doi:10.1016/0092-8674(93)90626-2. PMID 8269518.

[url_NYT-9] Angier N (1994-01-11). "Biologists Find Key Genes That Shape Patterning of Embryos". Science. New York Times.

[10] Anwood R (2007-09-06). Emus Can't Walk Backwards. Ebury Press. s. 113-114. ISBN 978-0-09-192151-4.

[11] Tom Simonite (2005-12-15). "Pokémon blocks gene name". Vol. 438, no. 897. Nature. doi:10.1038/438897a. Hentet 2013-05-23.

[nyt1994-12] "A Gene Named Sonic". The New York Times. 1994-01-11.

[13] Annalise Keen & Cliff Tabin (12. april 2004). "Cliff Tabin: Super Sonic An Interview". The Weekly Murmur. Arkiveret fra originalen 10. november 2005. Hentet 27. januar 2018.

[pmid16421543-14] Maclean K (januar 2006). "Humour of gene names lost in translation to patients". Nature. 439 (7074): 266. doi:10.1038/439266d. PMID 16421543.

[pmid16718675-15] Cohen MM (juli 2006). "Problems in the naming of genes". Am. J. Med. Genet. A. 140 (13): 1483-4. doi:10.1002/ajmg.a.31264. PMID 16718675.

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