Reviewed, UniProtKB/Swiss-Prot Q15465 (SHH_HUMAN)

Names and origin

Protein names

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

Gene names

Name:

SHH

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	462 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	Binds to the patched (PTC) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes. In the absence of SHH, PTC represses the constitutive signaling activity of SMO. Also regulates another target, the gli oncogene. Intercellular 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 By similarity.
Subunit structure	Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus. N-product is active as a multimer By similarity.
Subcellular location	Sonic hedgehog protein C-product: Secreted › extracellular space By similarity. Note: The C-terminal peptide diffuses from the cell By similarity. Sonic hedgehog protein N-product: Cell membrane; Lipid-anchor By similarity. Note: The N-product either remains associated with lipid rafts at the cell surface, or forms freely diffusible active multimers with its hydrophobic lipid-modified N- and C-termini buried inside By similarity.
Tissue specificity	Expressed in fetal intestine, liver, lung, and kidney. Not expressed in adult tissues.
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). The N-product is the active species in both local and long-range signaling, whereas the C-product has no signaling activity. Cholesterylation is required for N-product targeting to lipid rafts and multimerization By similarity. N-palmitoylation of Cys-24 by HHAT is required for N-product multimerization and full activity By similarity.
Involvement in disease	Defects in SHH are the cause of microphthalmia isolated with coloboma type 5 (MCOPCB5) [MIM:611638]. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, cataract and other abnormalities like cataract may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Ref.16 Defects in SHH are the cause of holoprosencephaly type 3 (HPE3) [MIM:142945]. Holoprosencephaly (HPE) [MIM:236100] is the most common structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. The majority of HPE3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance have been described. Interestingly, up to 30% of obligate carriers of HPE3 gene in autosomal dominant pedigrees are clinically unaffected. Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Defects in SHH are a cause of solitary median maxillary central incisor (SMMCI) [MIM:147250]. SMMCI is a rare dental anomaly characterized by the congenital absence of one maxillary central incisor. Ref.14 Defects in SHH are the cause of triphalangeal thumb-polysyndactyly syndrome (TPTPS) [MIM:174500]. TPTPS is an autosomal dominant syndrome characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern during limb development. TPTPS mutations have been mapped to the 7q36 locus in the LMBR1 gene which contains in its intron 5 a long-range cis-regulatory element of SHH expression. Ref.8
Sequence similarities	Belongs to the hedgehog family.
Mass spectrometry	Molecular mass is 19.560 Da from positions 24 - 197. Determined by ESI. Soluble N-product, purified from insect cells. Ref.6 Molecular mass is 20.167 Da from positions 24 - 197. Determined by ESI. Membrane-bound N-product, purified from insect cells. Ref.6

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Disease	Disease mutation Holoprosencephaly Microphthalmia
Domain	Signal
Molecular function	Developmental protein Hydrolase Protease
PTM	Autocatalytic cleavage Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	androgen metabolic process Inferred from sequence or structural similarity. Source: UniProtKB axon guidance Inferred from sequence or structural similarity. Source: UniProtKB branching involved in ureteric bud morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB cell fate specification Inferred from sequence or structural similarity. Source: UniProtKB embryonic digit morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB epithelial-mesenchymal signaling involved in prostate gland development Inferred from direct assay. Source: MGI heart development Inferred from sequence or structural similarity. Source: UniProtKB hindbrain development Inferred from sequence or structural similarity. Source: UniProtKB intein-mediated protein splicing Inferred from electronic annotation. Source: InterPro lung development Inferred from sequence or structural similarity. Source: UniProtKB male genitalia development Inferred from sequence or structural similarity. Source: UniProtKB midbrain development Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB neural crest cell migration Inferred from sequence or structural similarity. Source: UniProtKB neuroblast proliferation Inferred from sequence or structural similarity. Source: UniProtKB neuron fate commitment Inferred from sequence or structural similarity. Source: UniProtKB patterning of blood vessels Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: InterPro salivary gland morphogenesis Inferred from sequence or structural similarity. Source: UniProtKB vasculogenesis Inferred from sequence or structural similarity. Source: UniProtKB ventral midline development Ref.10 Traceable author statement. Source: ProtInc
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell surface Inferred from sequence or structural similarity. Source: UniProtKB extracellular space Inferred from sequence or structural similarity. Source: UniProtKB membrane raft Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	laminin-1 binding Inferred from sequence or structural similarity. Source: UniProtKB 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 – 23	23	Ref.6
	Chain	24 – 462	439	Sonic hedgehog protein		PRO_0000013208
	Chain	24 – 197	174	Sonic hedgehog protein N-product		PRO_0000013209
	Chain	198 – 462	265	Sonic hedgehog protein C-product		PRO_0000013210
Regions
	Compositional bias	407 – 411	5	Poly-Gly
Sites
	Site	197 – 198	2	Cleavage; by autolysis By similarity
	Site	243	1	Involved in cholesterol transfer By similarity
	Site	267	1	Involved in auto-cleavage By similarity
	Site	270	1	Essential for auto-cleavage By similarity
Amino acid modifications
	Lipidation	24	1	N-palmitoyl cysteine
	Lipidation	197	1	Cholesterol glycine ester By similarity
	Glycosylation	278	1	N-linked (GlcNAc...) Ref.9
Natural variations
	Natural variant	6	1	R → T in HPE3. Ref.18		VAR_023804
	Natural variant	27	1	G → A in HPE3. Ref.17		VAR_039888
	Natural variant	31	1	G → R in HPE3. dbSNP rs28936675. Ref.10 Ref.11		VAR_003619
	Natural variant	88	1	D → V in HPE3; familial. Ref.13		VAR_009163
	Natural variant	100	1	Q → H in HPE3; sporadic. Ref.12 Ref.18		VAR_009164
	Natural variant	106 – 107	2	Missing in HPE3.		VAR_023805
	Natural variant	110	1	A → D in HPE3. Ref.18		VAR_023806
	Natural variant	111	1	I → F in SMMCI. Ref.14		VAR_017883
	Natural variant	111	1	I → N in HPE3. Ref.19		VAR_039889
	Natural variant	115	1	N → K in HPE3; familial. Ref.13		VAR_009165
	Natural variant	117	1	W → G in HPE3. Ref.10 Ref.11		VAR_003620
	Natural variant	117	1	W → R in HPE3. Ref.10 Ref.11		VAR_003621
	Natural variant	140	1	H → P in HPE3. Ref.15		VAR_039890
	Natural variant	140	1	H → Q in HPE3. Ref.20		VAR_039891
	Natural variant	150	1	T → R in HPE3. Ref.18		VAR_023807
	Natural variant	176 – 178	3	Missing in HPE3.		VAR_023808
	Natural variant	183	1	C → F in HPE3. Ref.15		VAR_039892
	Natural variant	188	1	E → Q in HPE3; familial. Ref.12 Ref.18		VAR_009166
	Natural variant	222	1	D → N in HPE3; familial. Ref.12 Ref.18		VAR_009167
	Natural variant	224	1	V → E in HPE3. Ref.11		VAR_009168
	Natural variant	226	1	A → T in HPE3; familial. Ref.11		VAR_009169
	Natural variant	236	1	S → R in HPE3; familial. Ref.13		VAR_009170
	Natural variant	263 – 269	7	Missing in HPE3; sporadic.		VAR_009171
	Natural variant	267	1	T → I in HPE3. Ref.17		VAR_039893
	Natural variant	271	1	L → P in HPE3. Ref.18		VAR_023809
	Natural variant	290	1	G → D in HPE3; sporadic. Ref.13		VAR_009172
	Natural variant	332	1	V → A in HPE3. Ref.18		VAR_023810
	Natural variant	347	1	P → Q in HPE3. Ref.18		VAR_023811
	Natural variant	354	1	I → T in HPE3. Ref.18		VAR_023812
	Natural variant	373	1	A → T in HPE3. Ref.17		VAR_039894
	Natural variant	378 – 380	3	Missing in HPE3; familial.		VAR_009173
	Natural variant	381	1	R → P in HPE3. Ref.18		VAR_023813
	Natural variant	383	1	A → T in HPE3; sporadic. Ref.11		VAR_009174
	Natural variant	401 – 408	8	Missing in ocular coloboma.		VAR_017884
	Natural variant	404 – 408	5	Missing in HPE3; familial.		VAR_009175
	Natural variant	424	1	P → A in HPE3; familial. Ref.13		VAR_009176
	Natural variant	436	1	S → L in HPE3; sporadic. Ref.13		VAR_009177
Experimental info
	Mutagenesis	24	1	C → S: Abolishes palmitoylation. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q15465-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: DD687AFA582A4749	FASTA	462	49,607
	10 20 30 40 50 60 MLLLARCLLL VLVSSLLVCS GLACGPGRGF GKRRHPKKLT PLAYKQFIPN VAEKTLGASG 70 80 90 100 110 120 RYEGKISRNS ERFKELTPNY NPDIIFKDEE NTGADRLMTQ RCKDKLNALA ISVMNQWPGV 130 140 150 160 170 180 KLRVTEGWDE DGHHSEESLH YEGRAVDITT SDRDRSKYGM LARLAVEAGF DWVYYESKAH 190 200 210 220 230 240 IHCSVKAENS VAAKSGGCFP GSATVHLEQG GTKLVKDLSP GDRVLAADDQ GRLLYSDFLT 250 260 270 280 290 300 FLDRDDGAKK VFYVIETREP RERLLLTAAH LLFVAPHNDS ATGEPEASSG SGPPSGGALG 310 320 330 340 350 360 PRALFASRVR PGQRVYVVAE RDGDRRLLPA AVHSVTLSEE AAGAYAPLTA QGTILINRVL 370 380 390 400 410 420 ASCYAVIEEH SWAHRAFAPF RLAHALLAAL APARTDRGGD SGGGDRGGGG GRVALTAPGA 430 440 450 460 ADAPGAGATA GIHWYSQLLY QIGTWLLDSE ALHPLGMAVK SS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog." Marigo V., Roberts D.J., Lee S.M.K., Tsukurov O., Levi T., Gastier J.M., Epstein D.J., Gilbert D.J., Copeland N.G., Seidman C.E., Jenkins N.A., Seidman J.G., McMahon A.P., Tabin C. Genomics 28:44-51(1995) [PubMed: 7590746] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal lung.
[2]	"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].
[3]	NIEHS SNPs program Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., 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 C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., 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 W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Identification of a palmitic acid-modified form of human Sonic hedgehog." Pepinsky R.B., Zeng C., Wen D., Rayhorn P., Baker D.P., Williams K.P., Bixler S.A., Ambrose C.M., Garber E.A., Miatkowski K., Taylor F.R., Wang E.A., Galdes A. J. Biol. Chem. 273:14037-14045(1998) [PubMed: 9593755] [Abstract] Cited for: PROTEIN SEQUENCE OF 24-32, PALMITOYLATION AT CYS-24, CHOLESTERYLATION, MUTAGENESIS OF CYS-24, MASS SPECTROMETRY.
[7]	"Products, genetic linkage and limb patterning activity of a murine hedgehog gene." Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K., Zhao R., Seldin M.F., Fallon J.F., Beachy P.A. Development 120:3339-3353(1994) [PubMed: 7720571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 119-167.
[8]	"A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly." Lettice L.A., Heaney S.J.H., Purdie L.A., Li L., de Beer P., Oostra B.A., Goode D., Elgar G., Hill R.E., de Graaff E. Hum. Mol. Genet. 12:1725-1735(2003) [PubMed: 12837695] [Abstract] Cited for: INVOLVEMENT IN TPTPS.
[9]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278, MASS SPECTROMETRY. Tissue: Plasma.
[10]	"Mutations in the human Sonic hedgehog gene cause holoprosencephaly." Roessler E., Belloni E., Gaudenz K., Jay P., Berta P., Scherer S.W., Tsui L.-C., Muenke M. Nat. Genet. 14:357-360(1996) [PubMed: 8896572] [Abstract] Cited for: VARIANTS HPE3 ARG-31; GLY-117 AND ARG-117.
[11]	"Mutations in the C-terminal domain of Sonic hedgehog cause holoprosencephaly." Roessler E., Belloni E., Gaudenz K., Vargas F., Scherer S.W., Tsui L.-C., Muenke M. Hum. Mol. Genet. 6:1847-1853(1997) [PubMed: 9302262] [Abstract] Cited for: VARIANTS HPE3 ARG-31; GLY-117; ARG-117; GLU-224; THR-226 AND THR-383.
[12]	"Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly." Odent S., Atti-Bitach T., Blayau M., Mathieu M., Aug J., Delezo de A.L., Gall J.Y., Le Marec B., Munnich A., David V., Vekemans M. Hum. Mol. Genet. 8:1683-1689(1999) [PubMed: 10441331] [Abstract] Cited for: VARIANTS HPE3 HIS-100; GLN-188 AND ASN-222.
[13]	"The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly." Nanni L., Ming J.E., Bocian M., Steinhaus K., Bianchi D.W., Die-Smulders C., Giannotti A., Imaizumi K., Jones K.L., Campo M.D., Martin R.A., Meinecke P., Pierpont M.E.M., Robin N.H., Young I.D., Roessler E., Muenke M. Hum. Mol. Genet. 8:2479-2488(1999) [PubMed: 10556296] [Abstract] Cited for: VARIANTS HPE3 VAL-88; LYS-115; ARG-236; 263-ARG--ALA-269 DEL; ASP-290; ALA-424 AND LEU-436.
[14]	"SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature." Nanni L., Ming J.E., Du Y., Hall R.K., Aldred M., Bankier A., Muenke M. Am. J. Med. Genet. 102:1-10(2001) [PubMed: 11471164] [Abstract] Cited for: VARIANT SMMCI PHE-111.
[15]	"Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly." Orioli I.M., Castilla E.E., Ming J.E., Nazer J., Burle de Aguiar M.J., Llerena J.C., Muenke M. Hum. Genet. 109:1-6(2001) [PubMed: 11479728] [Abstract] Cited for: VARIANTS HPE3 PRO-140 AND PHE-183.
[16]	"Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia." Schimmenti L.A., de la Cruz J., Lewis R.A., Karkera J.D., Manligas G.S., Roessler E., Muenke M. Am. J. Med. Genet. A 116:215-221(2003) [PubMed: 12503095] [Abstract] Cited for: VARIANT MCOPCB5 401-SER--GLY-408 DEL.
[17]	"Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation." Hehr U., Gross C., Diebold U., Wahl D., Beudt U., Heidemann P., Hehr A., Mueller D. Eur. J. Pediatr. 163:347-352(2004) [PubMed: 15107988] [Abstract] Cited for: VARIANTS HPE3 ALA-27; ILE-267 AND THR-373.
[18]	"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations." Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., Le Duff F., Durou M.-R., Odent S., David V. Hum. Mutat. 24:43-51(2004) [PubMed: 15221788] [Abstract] Cited for: VARIANTS HPE3 THR-6; HIS-100; 106-LEU-ASN-107 DEL; ASP-110; ARG-150; 176-GLU--LYS-178 DEL; GLN-188; ASN-222; PRO-271; ALA-332; GLN-347; THR-354 AND PRO-381.
[19]	"SHH Ile111Asp in alobar holoprosencephaly in a proposita, whose mother had only a solitary median maxillary incisor." El-Jaick K.B., Brunoni D., Castilla E.E., Moreira M.A., Orioli I.M. Am. J. Med. Genet. A 136:345-345(2005) [PubMed: 15942952] [Abstract] Cited for: VARIANT HPE3 ASN-111.
[20]	"Single median maxillary central incisor, hypophyseal tumor, and SHH mutation." Ribeiro L.A., Richieri-Costa A. Am. J. Med. Genet. A 136:346-347(2005) [PubMed: 15942953] [Abstract] Cited for: VARIANT HPE3 GLN-140.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

L38518 mRNA. Translation: AAA62179.1.
AY422195 Genomic DNA. Translation: AAQ87879.1.
AC002484 Genomic DNA. Translation: AAB67604.1.
AC078834 Genomic DNA. Translation: AAS01990.1.
CH236954 Genomic DNA. Translation: EAL23913.1.

IPI

IPI00017480.

RefSeq

NP_000184.1.

UniGene

Hs.164537

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3HO5	X-ray	3.01	H	29-197	[»]

SMR

Q15465. Positions 38-194.

ModBase

Search...

Protein-protein interaction databases

STRING

Q15465.

Protein family/group databases

MEROPS

C46.002.

Proteomic databases

PRIDE

Q15465.

Genome annotation databases

Ensembl

ENST00000297261; ENSP00000297261; ENSG00000164690; Homo sapiens. [Genome view]
ENST00000430104; ENSP00000396621; ENSG00000164690; Homo sapiens. [Genome view]
ENST00000435425; ENSP00000413871; ENSG00000164690; Homo sapiens. [Genome view]
ENST00000441114; ENSP00000410546; ENSG00000164690; Homo sapiens. [Genome view]

GeneID

6469.

KEGG

hsa:6469.

UCSC

uc003wmj.1. human.
uc003wmk.1. human.

Organism-specific databases

CTD

6469.

GeneCards

GC07M155288.

H-InvDB

HIX0033702.

HGNC

HGNC:10848. SHH.

HPA

CAB018966.

MIM

142945. phenotype.
147250. phenotype.
174500. phenotype.
600725. gene.
611638. phenotype.

Orphanet

98938. Colobomatous microphthalmia.
2162. Holoprosencephaly.
194. Ocular coloboma.
93336. Polydactyly of a triphalangeal thumb (PPD2).
2922. Polydactyly, preaxial.
2286. Solitary median maxillary central incisor syndrome.
2950. Triphalangeal thumb-polysyndactyly syndrome.
2948. Triphalangeal thumbs - duplication of the big toes, familial.

PharmGKB

PA35752.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q15465.

HOVERGEN

Q15465.

OMA

LGMAVKS.

Enzyme and pathway databases

Pathway_Interaction_DB

hnf3apathway. FOXA1 transcription factor network.
glypican_3pathway. Glypican 3 network.
hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.
hedgehog_2pathway. Signaling events mediated by the Hedgehog family.

Gene expression databases

ArrayExpress

Q15465.

Bgee

Q15465.

CleanEx

HS_SHH.

Genevestigator

Q15465.

GermOnline

ENSG00000164690. Homo sapiens.

Family and domain databases

InterPro

IPR003586. Hedgehog_hint_C.
IPR003587. Hedgehog_hint_N.
IPR000320. HH_signal.
IPR006141. Intein_splicing_site.
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]

PROSITE

PS50817. INTEIN_N_TER. 1 hit.
[Graphical view]

ProtoNet

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Other Resources

NextBio

25129.

SOURCE

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Entry information

Entry name

SHH_HUMAN

Accession

Primary (citable) accession number: Q15465
Secondary accession number(s): A4D247, Q75MC9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1996
Last modified:	November 3, 2009
This is version 118 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.