Sonic hedgehog protein


NameSonic hedgehog protein
SynonymsHHG-1 SHH
Gene NameSHH
OrganismHuman
Amino acid sequence
>lcl|BSEQ0013929|Sonic hedgehog protein
MLLLARCLLLVLVSSLLVCSGLACGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASG
RYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGV
KLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAH
IHCSVKAENSVAAKSGGCFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLT
FLDRDDGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSATGEPEASSGSGPPSGGALG
PRALFASRVRPGQRVYVVAERDGDRRLLPAAVHSVTLSEEAAGAYAPLTAQGTILINRVL
ASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDRGGDSGGGDRGGGGGRVALTAPGA
ADAPGAGATAGIHWYSQLLYQIGTWLLDSEALHPLGMAVKSS
Number of residues462
Molecular Weight49606.685
Theoretical pINone
GO Classification
Functions
    patched binding
    laminin-1 binding
    glycosaminoglycan binding
    zinc ion binding
    calcium ion binding
    morphogen activity
    peptidase activity
Processes
    intein-mediated protein splicing
    negative regulation of transcription from RNA polymerase II promoter
    right lung development
    negative regulation of proteasomal ubiquitin-dependent protein catabolic process
    epithelial cell proliferation involved in salivary gland morphogenesis
    palate development
    negative regulation of ureter smooth muscle cell differentiation
    patterning of blood vessels
    positive regulation of transcription, DNA-templated
    positive regulation of T cell differentiation in thymus
    camera-type eye development
    canonical Wnt signaling pathway
    dorsal/ventral pattern formation
    left lung development
    negative regulation of cell differentiation
    smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation
    salivary gland cavitation
    hair follicle morphogenesis
    Bergmann glial cell differentiation
    neuroblast proliferation
    apoptotic signaling pathway
    protein localization to nucleus
    positive regulation of ureter smooth muscle cell differentiation
    central nervous system development
    cell fate specification
    lung epithelium development
    thalamus development
    somite development
    positive regulation of immature T cell proliferation in thymus
    limb bud formation
    intermediate filament organization
    neuron fate commitment
    negative thymic T cell selection
    lung development
    primary prostatic bud elongation
    spinal cord motor neuron differentiation
    ectoderm development
    lymphoid progenitor cell differentiation
    myotube differentiation
    striated muscle tissue development
    embryo development
    lung lobe morphogenesis
    hindbrain development
    organ formation
    forebrain development
    heart development
    regulation of mesenchymal cell proliferation involved in prostate gland development
    pancreas development
    embryonic digit morphogenesis
    bud outgrowth involved in lung branching
    mesenchymal smoothened signaling pathway involved in prostate gland development
    negative regulation of T cell proliferation
    telencephalon regionalization
    artery development
    positive regulation of smoothened signaling pathway
    lung-associated mesenchyme development
    cell development
    cell-cell signaling
    pattern specification process
    embryonic hindlimb morphogenesis
    negative regulation of apoptotic process
    regulation of nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry
    androgen metabolic process
    embryonic foregut morphogenesis
    CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
    positive regulation of protein import into nucleus
    metanephric mesenchymal cell proliferation involved in metanephros development
    positive regulation of oligodendrocyte differentiation
    thyroid gland development
    negative regulation of canonical Wnt signaling pathway
    mesenchymal cell proliferation involved in lung development
    embryonic limb morphogenesis
    polarity specification of anterior/posterior axis
    positive regulation of cell division
    positive regulation of transcription from RNA polymerase II promoter
    regulation of odontogenesis
    prostate gland development
    embryonic forelimb morphogenesis
    establishment of cell polarity
    multicellular structure septum development
    odontogenesis of dentin-containing tooth
    trachea morphogenesis
    myoblast differentiation
    midbrain development
    cerebellar granule cell precursor proliferation
    positive regulation of hh target transcription factor activity
    dorsal/ventral neural tube patterning
    smoothened signaling pathway
    regulation of prostatic bud formation
    osteoblast development
    positive regulation of epithelial cell proliferation involved in prostate gland development
    oligodendrocyte development
    blood coagulation
    negative regulation of alpha-beta T cell differentiation
    inner ear development
    ventral midline development
    positive regulation of skeletal muscle tissue development
    positive regulation of kidney smooth muscle cell differentiation
    negative regulation of cholesterol efflux
    positive regulation of Wnt signaling pathway
    stem cell development
    axon guidance
    epithelial-mesenchymal signaling involved in prostate gland development
    positive regulation of cell proliferation
    regulation of protein localization to nucleus
    positive regulation of neuroblast proliferation
    heart looping
    negative regulation of kidney smooth muscle cell differentiation
    negative regulation of cell migration
    branching involved in salivary gland morphogenesis
    positive regulation of mesenchymal cell proliferation involved in ureter development
    endocytosis
    prostate epithelial cord elongation
    regulation of cell proliferation
    formation of anatomical boundary
    regulation of proteolysis
    T cell differentiation in thymus
    embryonic digestive tract morphogenesis
    metanephros development
    negative regulation of mesenchymal cell apoptotic process
    positive regulation of alpha-beta T cell differentiation
    positive regulation of sclerotome development
    male genitalia development
    vasculogenesis
    determination of left/right asymmetry in lateral mesoderm
    hindgut morphogenesis
    cellular response to lithium ion
    renal system development
    thymus development
    embryonic pattern specification
    positive thymic T cell selection
    negative regulation of transcription elongation from RNA polymerase II promoter
    neural crest cell migration
    embryonic skeletal system development
    positive regulation of skeletal muscle cell proliferation
    branching morphogenesis of an epithelial tube
    branching involved in ureteric bud morphogenesis
    positive regulation of striated muscle cell differentiation
Components
    nucleus
    plasma membrane
    extracellular space
    cell surface
    proteinaceous extracellular matrix
    cytosol
    membrane raft
    endoplasmic reticulum lumen
    extracellular region
General FunctionZinc ion binding
Specific FunctionIntercellular signal essential for a variety of patterning events during development: signal produced by the notochord that induces ventral cell fate in the neural tube and somites, and the polarizing signal for patterning of the anterior-posterior axis of the developing limb bud. Displays both floor plate- and motor neuron-inducing activity. The threshold concentration of N-product required for motor neuron induction is 5-fold lower than that required for floor plate induction. Activates the transcription of target genes by interacting with its receptor PTCH1 to prevent normal inhibition by PTCH1 on the constitutive signaling activity of SMO (By similarity).
Transmembrane Regions
GenBank Protein ID
UniProtKB IDQ15465
UniProtKB Entry NameSHH_HUMAN
Cellular LocationSecreted
Gene sequence
>lcl|BSEQ0013930|Sonic hedgehog protein (SHH)
ATGCTGCTGCTGGCGAGATGTCTGCTGCTAGTCCTCGTCTCCTCGCTGCTGGTATGCTCG
GGACTGGCGTGCGGACCGGGCAGGGGGTTCGGGAAGAGGAGGCACCCCAAAAAGCTGACC
CCTTTAGCCTACAAGCAGTTTATCCCCAATGTGGCCGAGAAGACCCTAGGCGCCAGCGGA
AGGTATGAAGGGAAGATCTCCAGAAACTCCGAGCGATTTAAGGAACTCACCCCCAATTAC
AACCCCGACATCATATTTAAGGATGAAGAAAACACCGGAGCGGACAGGCTGATGACTCAG
AGGTGTAAGGACAAGTTGAACGCTTTGGCCATCTCGGTGATGAACCAGTGGCCAGGAGTG
AAACTGCGGGTGACCGAGGGCTGGGACGAAGATGGCCACCACTCAGAGGAGTCTCTGCAC
TACGAGGGCCGCGCAGTGGACATCACCACGTCTGACCGCGACCGCAGCAAGTACGGCATG
CTGGCCCGCCTGGCGGTGGAGGCCGGCTTCGACTGGGTGTACTACGAGTCCAAGGCACAT
ATCCACTGCTCGGTGAAAGCAGAGAACTCGGTGGCGGCCAAATCGGGAGGCTGCTTCCCG
GGCTCGGCCACGGTGCACCTGGAGCAGGGCGGCACCAAGCTGGTGAAGGACCTGAGCCCC
GGGGACCGCGTGCTGGCGGCGGACGACCAGGGCCGGCTGCTCTACAGCGACTTCCTCACT
TTCCTGGACCGCGACGACGGCGCCAAGAAGGTCTTCTACGTGATCGAGACGCGGGAGCCG
CGCGAGCGCCTGCTGCTCACCGCCGCGCACCTGCTCTTTGTGGCGCCGCACAACGACTCG
GCCACCGGGGAGCCCGAGGCGTCCTCGGGCTCGGGGCCGCCTTCCGGGGGCGCACTGGGG
CCTCGGGCGCTGTTCGCCAGCCGCGTGCGCCCGGGCCAGCGCGTGTACGTGGTGGCCGAG
CGTGACGGGGACCGCCGGCTCCTGCCCGCCGCTGTGCACAGCGTGACCCTAAGCGAGGAG
GCCGCGGGCGCCTACGCGCCGCTCACGGCCCAGGGCACCATTCTCATCAACCGGGTGCTG
GCCTCGTGCTACGCGGTCATCGAGGAGCACAGCTGGGCGCACCGGGCCTTCGCGCCCTTC
CGCCTGGCGCACGCGCTCCTGGCTGCACTGGCGCCCGCGCGCACGGACCGCGGCGGGGAC
AGCGGCGGCGGGGACCGCGGGGGCGGCGGCGGCAGAGTAGCCCTAACCGCTCCAGGTGCT
GCCGACGCTCCGGGTGCGGGGGCCACCGCGGGCATCCACTGGTACTCGCAGCTGCTCTAC
CAAATAGGCACCTGGCTCCTGGACAGCGAGGCCCTGCACCCGCTGGGCATGGCGGTCAAG
TCCAGCTGA
GenBank Gene ID
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:10848
Chromosome Location7
LocusNone
References
  1. Maun HR, Wen X, Lingel A, de Sauvage FJ, Lazarus RA, Scales SJ, Hymowitz SG: Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site. J Biol Chem. 2010 Aug 20;285(34):26570-80. doi: 10.1074/jbc.M110.112284. Epub 2010 May 26.[20504762 ]
  2. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64.[12853948 ]
  3. Nanni L, Ming JE, Bocian M, Steinhaus K, Bianchi DW, Die-Smulders C, Giannotti A, Imaizumi K, Jones KL, Campo MD, Martin RA, Meinecke P, Pierpont ME, Robin NH, Young ID, Roessler E, Muenke M: The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Hum Mol Genet. 1999 Dec;8(13):2479-88.[10556296 ]
  4. Richieri-Costa A, Ribeiro LA: Holoprosencephaly-like phenotype: clinical and genetic perspectives. Am J Med Genet A. 2006 Dec 1;140(23):2587-93.[17001669 ]
  5. Marigo V, Roberts DJ, Lee SM, Tsukurov O, Levi T, Gastier JM, Epstein DJ, Gilbert DJ, Copeland NG, Seidman CE, et al.: Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. Genomics. 1995 Jul 1;28(1):44-51.[7590746 ]
  6. Roessler E, El-Jaick KB, Dubourg C, Velez JI, Solomon BD, Pineda-Alvarez DE, Lacbawan F, Zhou N, Ouspenskaia M, Paulussen A, Smeets HJ, Hehr U, Bendavid C, Bale S, Odent S, David V, Muenke M: The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis. Hum Mutat. 2009 Oct;30(10):E921-35. doi: 10.1002/humu.21090.[19603532 ]
  7. Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC: Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10.[12690205 ]
  8. Pepinsky RB, Zeng C, Wen D, Rayhorn P, Baker DP, Williams KP, Bixler SA, Ambrose CM, Garber EA, Miatkowski K, Taylor FR, Wang EA, Galdes A: Identification of a palmitic acid-modified form of human Sonic hedgehog. J Biol Chem. 1998 May 29;273(22):14037-45.[9593755 ]
  9. Chang DT, Lopez A, von Kessler DP, Chiang C, Simandl BK, Zhao R, Seldin MF, Fallon JF, Beachy PA: Products, genetic linkage and limb patterning activity of a murine hedgehog gene. Development. 1994 Nov;120(11):3339-53.[7720571 ]
  10. Lettice LA, Heaney SJ, Purdie LA, Li L, de Beer P, Oostra BA, Goode D, Elgar G, Hill RE, de Graaff E: A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum Mol Genet. 2003 Jul 15;12(14):1725-35.[12837695 ]
  11. Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. J Proteome Res. 2005 Nov-Dec;4(6):2070-80.[16335952 ]
  12. Sun M, Ma F, Zeng X, Liu Q, Zhao XL, Wu FX, Wu GP, Zhang ZF, Gu B, Zhao YF, Tian SH, Lin B, Kong XY, Zhang XL, Yang W, Lo WH, Zhang X: Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb-specific SHH enhancer. J Med Genet. 2008 Sep;45(9):589-95. doi: 10.1136/jmg.2008.057646. Epub 2008 Apr 16.[18417549 ]
  13. Wieczorek D, Pawlik B, Li Y, Akarsu NA, Caliebe A, May KJ, Schweiger B, Vargas FR, Balci S, Gillessen-Kaesbach G, Wollnik B: A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb. Hum Mutat. 2010 Jan;31(1):81-9. doi: 10.1002/humu.21142.[19847792 ]
  14. Lohan S, Spielmann M, Doelken SC, Flottmann R, Muhammad F, Baig SM, Wajid M, Hulsemann W, Habenicht R, Kjaer KW, Patil SJ, Girisha KM, Abarca-Barriga HH, Mundlos S, Klopocki E: Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome. Clin Genet. 2014 Oct;86(4):318-25. doi: 10.1111/cge.12352. Epub 2014 Feb 17.[24456159 ]
  15. Norbnop P, Srichomthong C, Suphapeetiporn K, Shotelersuk V: ZRS 406A>G mutation in patients with tibial hypoplasia, polydactyly and triphalangeal first fingers. J Hum Genet. 2014 Aug;59(8):467-70. doi: 10.1038/jhg.2014.50. Epub 2014 Jun 26.[24965254 ]
  16. Pepinsky RB, Rayhorn P, Day ES, Dergay A, Williams KP, Galdes A, Taylor FR, Boriack-Sjodin PA, Garber EA: Mapping sonic hedgehog-receptor interactions by steric interference. J Biol Chem. 2000 Apr 14;275(15):10995-1001.[10753901 ]
  17. Bosanac I, Maun HR, Scales SJ, Wen X, Lingel A, Bazan JF, de Sauvage FJ, Hymowitz SG, Lazarus RA: The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling. Nat Struct Mol Biol. 2009 Jul;16(7):691-7. doi: 10.1038/nsmb.1632. Epub 2009 Jun 28.[19561609 ]
  18. Roessler E, Belloni E, Gaudenz K, Jay P, Berta P, Scherer SW, Tsui LC, Muenke M: Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. Nat Genet. 1996 Nov;14(3):357-60.[8896572 ]
  19. Roessler E, Belloni E, Gaudenz K, Vargas F, Scherer SW, Tsui LC, Muenke M: Mutations in the C-terminal domain of Sonic Hedgehog cause holoprosencephaly. Hum Mol Genet. 1997 Oct;6(11):1847-53.[9302262 ]
  20. Odent S, Atti-Bitach T, Blayau M, Mathieu M, Aug J, Delezo de AL, Gall JY, Le Marec B, Munnich A, David V, Vekemans M: Expression of the Sonic hedgehog (SHH ) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. Hum Mol Genet. 1999 Sep;8(9):1683-9.[10441331 ]
  21. Nanni L, Ming JE, Du Y, Hall RK, Aldred M, Bankier A, Muenke M: SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature. Am J Med Genet. 2001 Jul 22;102(1):1-10.[11471164 ]
  22. Orioli IM, Castilla EE, Ming JE, Nazer J, Burle de Aguiar MJ, Llerena JC, Muenke M: Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly. Hum Genet. 2001 Jul;109(1):1-6.[11479728 ]
  23. Schimmenti LA, de la Cruz J, Lewis RA, Karkera JD, Manligas GS, Roessler E, Muenke M: Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia. Am J Med Genet A. 2003 Jan 30;116A(3):215-21.[12503095 ]
  24. Garavelli L, Zanacca C, Caselli G, Banchini G, Dubourg C, David V, Odent S, Gurrieri F, Neri G: Solitary median maxillary central incisor syndrome: clinical case with a novel mutation of sonic hedgehog. Am J Med Genet A. 2004 May 15;127A(1):93-5.[15103725 ]
  25. Hehr U, Gross C, Diebold U, Wahl D, Beudt U, Heidemann P, Hehr A, Mueller D: Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation. Eur J Pediatr. 2004 Jul;163(7):347-52. Epub 2004 Apr 24.[15107988 ]
  26. Dubourg C, Lazaro L, Pasquier L, Bendavid C, Blayau M, Le Duff F, Durou MR, Odent S, David V: Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations. Hum Mutat. 2004 Jul;24(1):43-51.[15221788 ]
  27. El-Jaick KB, Brunoni D, Castilla EE, Moreira MA, Orioli IM: SHH Ile111Asp in alobar holoprosencephaly in a proposita, whose mother had only a solitary median maxillary incisor. Am J Med Genet A. 2005 Aug 1;136A(4):345.[15942952 ]
  28. Ribeiro LA, Richieri-Costa A: Single median maxillary central incisor, hypophyseal tumor, and SHH mutation. Am J Med Genet A. 2005 Aug 1;136A(4):346-7.[15942953 ]
  29. Maity T, Fuse N, Beachy PA: Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17026-31. Epub 2005 Nov 10.[16282375 ]

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