LOCUS       NM_000193               4650 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens sonic hedgehog signaling molecule (SHH), transcript
            variant 1, mRNA.
ACCESSION   NM_000193
VERSION     NM_000193.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4650)
  AUTHORS   Yamada,M., Mizuno,S., Inaba,M., Uehara,T., Inagaki,H., Suzuki,H.,
            Miya,F., Takenouchi,T., Kurahashi,H. and Kosaki,K.
  TITLE     Truncating variants of the sterol recognition region of SHH cause
            hypertelorism phenotype rather than hypotelorism-holoprosencephaly
  JOURNAL   Am J Med Genet A 194 (8), e63614 (2024)
   PUBMED   38562108
  REMARK    GeneRIF: Truncating variants of the sterol recognition region of
            SHH cause hypertelorism phenotype rather than
            hypotelorism-holoprosencephaly.
REFERENCE   2  (bases 1 to 4650)
  AUTHORS   Guyodo,H., Rizzo,A., Diab,F., Noury,F., Mironov,S., de Tayrac,M.,
            David,V., Odent,S., Dubourg,C. and Dupe,V.
  TITLE     Impact of Sonic Hedgehog-dependent sphenoid bone defect on
            craniofacial growth
  JOURNAL   Clin Exp Dent Res 10 (2), e861 (2024)
   PUBMED   38558491
  REMARK    GeneRIF: Impact of Sonic Hedgehog-dependent sphenoid bone defect on
            craniofacial growth.
REFERENCE   3  (bases 1 to 4650)
  AUTHORS   Zeng,L.H., Tang,C., Yao,M., He,Q., Qv,M., Ren,Q., Xu,Y., Shen,T.,
            Gu,W., Xu,C., Zou,C., Ji,X., Wu,X. and Wang,J.
  TITLE     Phosphorylation of human glioma-associated oncogene 1 on Ser937
            regulates Sonic Hedgehog signaling in medulloblastoma
  JOURNAL   Nat Commun 15 (1), 987 (2024)
   PUBMED   38307877
  REMARK    GeneRIF: Phosphorylation of human glioma-associated oncogene 1 on
            Ser937 regulates Sonic Hedgehog signaling in medulloblastoma.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4650)
  AUTHORS   Lospinoso Severini,L., Loricchio,E., Navacci,S., Basili,I.,
            Alfonsi,R., Bernardi,F., Moretti,M., Conenna,M., Cucinotta,A.,
            Coni,S., Petroni,M., De Smaele,E., Giannini,G., Maroder,M.,
            Canettieri,G., Mastronuzzi,A., Guardavaccaro,D., Ayrault,O.,
            Infante,P., Bufalieri,F. and Di Marcotullio,L.
  TITLE     SALL4 is a CRL3REN/KCTD11 substrate that drives Sonic
            Hedgehog-dependent medulloblastoma
  JOURNAL   Cell Death Differ 31 (2), 170-187 (2024)
   PUBMED   38062245
  REMARK    GeneRIF: SALL4 is a CRL3[REN/KCTD11] substrate that drives Sonic
            Hedgehog-dependent medulloblastoma.
REFERENCE   5  (bases 1 to 4650)
  AUTHORS   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. and Galdes,A.
  TITLE     Identification of a palmitic acid-modified form of human Sonic
            hedgehog
  JOURNAL   J Biol Chem 273 (22), 14037-14045 (1998)
   PUBMED   9593755
REFERENCE   6  (bases 1 to 4650)
  AUTHORS   Marigo,V., Roberts,D.J., Lee,S.M., Tsukurov,O., Levi,T.,
            Gastier,J.M., Epstein,D.J., Gilbert,D.J., Copeland,N.G.,
            Seidman,C.E. et al.
  TITLE     Cloning, expression, and chromosomal location of SHH and IHH: two
            human homologues of the Drosophila segment polarity gene hedgehog
  JOURNAL   Genomics 28 (1), 44-51 (1995)
   PUBMED   7590746
REFERENCE   7  (bases 1 to 4650)
  AUTHORS   Chang,D.T., Lopez,A., von Kessler,D.P., Chiang,C., Simandl,B.K.,
            Zhao,R., Seldin,M.F., Fallon,J.F. and Beachy,P.A.
  TITLE     Products, genetic linkage and limb patterning activity of a murine
            hedgehog gene
  JOURNAL   Development 120 (11), 3339-3353 (1994)
   PUBMED   7720571
REFERENCE   8  (bases 1 to 4650)
  AUTHORS   Tsukurov,O., Boehmer,A., Flynn,J., Nicolai,J.P., Hamel,B.C.,
            Traill,S., Zaleske,D., Mankin,H.J., Yeon,H., Ho,C. et al.
  TITLE     A complex bilateral polysyndactyly disease locus maps to chromosome
            7q36
  JOURNAL   Nat Genet 6 (3), 282-286 (1994)
   PUBMED   8012391
REFERENCE   9  (bases 1 to 4650)
  AUTHORS   Tekendo-Ngongang,C., Muenke,M. and Kruszka,P.
  TITLE     Holoprosencephaly Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301702
REFERENCE   10 (bases 1 to 4650)
  AUTHORS   Bardakjian,T., Weiss,A. and Schneider,A.
  TITLE     Microphthalmia/Anophthalmia/Coloboma Spectrum - RETIRED CHAPTER,
            FOR HISTORICAL REFERENCE ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301552
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC078834.5, L38518.1,
            BX452210.1, BY797055.2 and BX109787.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_000193.3.
            
            Summary: This gene encodes a protein that is instrumental in
            patterning the early embryo. It has been implicated as the key
            inductive signal in patterning of the ventral neural tube, the
            anterior-posterior limb axis, and the ventral somites. Of three
            human proteins showing sequence and functional similarity to the
            sonic hedgehog protein of Drosophila, this protein is the most
            similar. The protein is made as a precursor that is
            autocatalytically cleaved; the N-terminal portion is soluble and
            contains the signalling activity while the C-terminal portion is
            involved in precursor processing. More importantly, the C-terminal
            product covalently attaches a cholesterol moiety to the N-terminal
            product, restricting the N-terminal product to the cell surface and
            preventing it from freely diffusing throughout the developing
            embryo. Defects in this protein or in its signalling pathway are a
            cause of holoprosencephaly (HPE), a disorder in which the
            developing forebrain fails to correctly separate into right and
            left hemispheres. HPE is manifested by facial deformities. It is
            also thought that mutations in this gene or in its signalling
            pathway may be responsible for VACTERL syndrome, which is
            characterized by vertebral defects, anal atresia, tracheoesophageal
            fistula with esophageal atresia, radial and renal dysplasia,
            cardiac anomalies, and limb abnormalities. Additionally, mutations
            in a long range enhancer located approximately 1 megabase upstream
            of this gene disrupt limb patterning and can result in preaxial
            polydactyly. [provided by RefSeq, Jul 2008].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longer isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR14038191.240896.1,
                                           SRR14038193.1138684.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMN03267752,
                                           SAMN03267759 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            CDS uses downstream in-frame AUG :: experimental evidence (PMID:
                                                9593755)
            MANE Ensembl match               :: ENST00000297261.7/
                                                ENSP00000297261.2
            RefSeq Select criteria           :: based on conservation,
                                                expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-190               AC078834.5         104083-104272       c
            191-293             L38518.1           1-103
            294-294             BX452210.1         13-13
            295-1765            L38518.1           105-1575
            1766-1773           AC078834.5         94666-94673         c
            1774-1837           BY797055.2         1-64
            1838-1956           BX109787.1         1-119
            1957-1957           BY797055.2         184-184
            1958-2390           BX109787.1         121-553
            2391-4650           AC078834.5         91789-94048         c
FEATURES             Location/Qualifiers
     source          1..4650
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="7"
                     /map="7q36.3"
     gene            1..4650
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="sonic hedgehog signaling molecule"
                     /db_xref="GeneID:6469"
                     /db_xref="HGNC:HGNC:10848"
                     /db_xref="MIM:600725"
     exon            1..641
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /inference="alignment:Splign:2.1.0"
     CDS             342..1730
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1; sonic hedgehog homolog; shh unprocessed
                     N-terminal signaling and C-terminal autoprocessing
                     domains"
                     /codon_start=1
                     /product="sonic hedgehog protein isoform 1 preproprotein"
                     /protein_id="NP_000184.1"
                     /db_xref="CCDS:CCDS5942.1"
                     /db_xref="GeneID:6469"
                     /db_xref="HGNC:HGNC:10848"
                     /db_xref="MIM:600725"
                     /translation="MLLLARCLLLVLVSSLLVCSGLACGPGRGFGKRRHPKKLTPLAY
                     KQFIPNVAEKTLGASGRYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRC
                     KDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGM
                     LARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPGSATVHLEQGGTKLVKDL
                     SPGDRVLAADDQGRLLYSDFLTFLDRDDGAKKVFYVIETREPRERLLLTAAHLLFVAP
                     HNDSATGEPEASSGSGPPSGGALGPRALFASRVRPGQRVYVVAERDGDRRLLPAAVHS
                     VTLSEEAAGAYAPLTAQGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAP
                     ARTDRGGDSGGGDRGGGGGRVALTAPGAADAPGAGATAGIHWYSQLLYQIGTWLLDSE
                     ALHPLGMAVKSS"
     exon            642..903
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /inference="alignment:Splign:2.1.0"
     exon            904..4650
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2023..2028
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="hexamer: AATAAT"
     polyA_site      2055
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="major polyA site"
     regulatory      2763..2768
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="hexamer: AATAAA"
     polyA_site      2806
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="major polyA site"
     polyA_site      2809
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="major polyA site"
     regulatory      4627..4632
                     /regulatory_class="polyA_signal_sequence"
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="hexamer: ATTAAA"
     polyA_site      4650
                     /gene="SHH"
                     /gene_synonym="HHG1; HLP3; HPE3; MCOPCB5; ShhNC; SMMCI;
                     TPT; TPTPS"
                     /note="major polyA site"
ORIGIN      
        1 acaagctctc caggcttgct accatttaaa atcagactct ttttgtcttt tgattgctgt
       61 ctcgcgaccc aactccgatg tgttccgtta tcagcggccg gcagcctgcc attccagccc
      121 ctgtctgggt ggggagcggt ggagagtccc ccgcagccgc ggcgggcaag gttatatagg
      181 aagagaaaga gcgaggcagc cagcgaggga gagagcgagc gggcgagccg gagcgaggaa
      241 gggaaagcgc aagagagagc gcacacgcac acacccgccg cgcgcactcg cgcacggacc
      301 cgcacgggga cagctcggaa gtcatcagtt ccatgggcga gatgctgctg ctggcgagat
      361 gtctgctgct agtcctcgtc tcctcgctgc tggtatgctc gggactggcg tgcggaccgg
      421 gcagggggtt cgggaagagg aggcacccca aaaagctgac ccctttagcc tacaagcagt
      481 ttatccccaa tgtggccgag aagaccctag gcgccagcgg aaggtatgaa gggaagatct
      541 ccagaaactc cgagcgattt aaggaactca cccccaatta caaccccgac atcatattta
      601 aggatgaaga aaacaccgga gcggacaggc tgatgactca gaggtgtaag gacaagttga
      661 acgctttggc catctcggtg atgaaccagt ggccaggagt gaaactgcgg gtgaccgagg
      721 gctgggacga agatggccac cactcagagg agtctctgca ctacgagggc cgcgcagtgg
      781 acatcaccac gtctgaccgc gaccgcagca agtacggcat gctggcccgc ctggcggtgg
      841 aggccggctt cgactgggtg tactacgagt ccaaggcaca tatccactgc tcggtgaaag
      901 cagagaactc ggtggcggcc aaatcgggag gctgcttccc gggctcggcc acggtgcacc
      961 tggagcaggg cggcaccaag ctggtgaagg acctgagccc cggggaccgc gtgctggcgg
     1021 cggacgacca gggccggctg ctctacagcg acttcctcac tttcctggac cgcgacgacg
     1081 gcgccaagaa ggtcttctac gtgatcgaga cgcgggagcc gcgcgagcgc ctgctgctca
     1141 ccgccgcgca cctgctcttt gtggcgccgc acaacgactc ggccaccggg gagcccgagg
     1201 cgtcctcggg ctcggggccg ccttccgggg gcgcactggg gcctcgggcg ctgttcgcca
     1261 gccgcgtgcg cccgggccag cgcgtgtacg tggtggccga gcgtgacggg gaccgccggc
     1321 tcctgcccgc cgctgtgcac agcgtgaccc taagcgagga ggccgcgggc gcctacgcgc
     1381 cgctcacggc ccagggcacc attctcatca accgggtgct ggcctcgtgc tacgcggtca
     1441 tcgaggagca cagctgggcg caccgggcct tcgcgccctt ccgcctggcg cacgcgctcc
     1501 tggctgcact ggcgcccgcg cgcacggacc gcggcgggga cagcggcggc ggggaccgcg
     1561 ggggcggcgg cggcagagta gccctaaccg ctccaggtgc tgccgacgct ccgggtgcgg
     1621 gggccaccgc gggcatccac tggtactcgc agctgctcta ccaaataggc acctggctcc
     1681 tggacagcga ggccctgcac ccgctgggca tggcggtcaa gtccagctga agccgggggg
     1741 ccgggggagg ggcgcgggag ggggcggggc ggggcagcaa cagcaacgca aagcaaaaag
     1801 acactcggaa aaggcgcacg aaccagactg agttataata agaataagaa taataaagta
     1861 ggacagtcca aagtagactc taaggaaaca aggaccccgg gaagttttgt tgttgtgctt
     1921 agttgatata tattttttga atttttttgg ttattgtttt attttggtta ttttttcctc
     1981 ctctcctggc tatttatttg tttggtatga atagatgttt taaataatat gaaccggacc
     2041 ttcaagagcc ttaaatagtt tgtttcttgg ataatttatt atgatcatgt gaactgtact
     2101 cacgggggaa agattatttt gtgaggccaa gcaacctgct cagagtctat ttttctacat
     2161 gtccctcgtc ccggctgtca gaaagcaaac ctctgtcccc gccatccctc ccttccatct
     2221 cctgcttctc agcaagtgca aactcaaacg tgcttcatgg gggtccacaa attatatttt
     2281 tatacacaga attgtaaatt agattttttg agagatcaat acttaactga attacatttc
     2341 atttttgaaa tagtgtaaaa tatgaaaata tattatttta atttaactag tttccgatgt
     2401 aacagccatc tcctctgttg tctttatggt ttcatattcc ctttgtattc accattttgc
     2461 cacattcttg gaagccaaga ctgttacaca cacaacatac acacacactt ttctttttct
     2521 tttcttttct tttttttttt tttttttttt tttggacaaa ctggaagaac tgttattttt
     2581 aacttcaaag aatttattag aaaataatat tttttaaaag cgcacatagt gacgagccca
     2641 cgaggatgga gcctgcagtt tgtacagaga aaacaaagga tgtttttgca ttaataaatt
     2701 gagaaataac gctgtaaatt tactaaaatg tatttttgaa tattttgtaa tagttttata
     2761 gaaataaaat gtgccatgca cagaacgctt agtatctaat aactaagaat tcctgttgca
     2821 gccctttttc ttttagtttt tggcttcttt gtttgggaaa cctagcgctg acaggagctc
     2881 ccaatattct atttagatgt gttgcttata ctgtgaactc agactgactg acttaggtaa
     2941 ccaaagtagg cacacaaacc aacttgtttc ttctcatggc tggagaaacc tcagctctgt
     3001 ttgtatttat tgtgtgaagc tctttctaca ctcccaaagg ttgggagtgc cattcgtggg
     3061 gactgtgctg tccccctcac cccacccctt aactagcaaa gcctgatgtg taagcccaga
     3121 ggaggtggcc tggggatggc caccaacaac cttctcttag gactcctgtg tgtggttgct
     3181 gggcagaccc ctggcctgac cctgtttgtg cttctctgat ctgtagggag gaggctcatt
     3241 gctgctttct gaggtcctgt tgtgtccctt ccagaaagca tccttagaag agaggacccg
     3301 gtttgatctt ctctgaagct cctatcctct tttcttgagg gtccccttaa atctgagtgg
     3361 caagcccaca gtggcgaggg ccagtcgctg gaatgtcggg gctgctgttg aggtcctcag
     3421 gctacactgg ttgtctgtgt cacatggcgg tcgggcgtgg actttgatcc ctgttgagag
     3481 agcatgctgc tgtgggcgct gggctgggga aggtccttcc atgcttcatg ctgccttgga
     3541 ggtttggcca agagggtctc tgcccttggc ggttgtcagg gtcccaggtg gaggactact
     3601 cccagttctt tggcttacgg aaggtgtctg ccatgctttg tgctttgggc cgaatcgtct
     3661 gagcaggctg ggccttggaa gagttgcgct gcatgagctt ggggcctccc agcagctgca
     3721 gcctgtgtag aaggtggtcc aggcttaggg aacaggagtg aacagacttc agccccacct
     3781 ggcaggggct ggctcccgag gttgggccca gtccctgagg gtctgctctg ctacgggtct
     3841 gcccttgagt ggccttccgt ggagggtgtg tgaccaggtg gatggcgcag ggcctctgga
     3901 gccctctcct caggagcagt cctcagcctt tttctgtaaa agacttttct ttggtgttct
     3961 aggtggtcag caggttccag gctggtgttt acaatctcgg aggaagtgcg atggtttctg
     4021 ttcttttgac agttcagtct gatttcaagt cagtcgaaag cgaaccagaa gcaccgggca
     4081 cagcagctcc tctggctgtg tagacagacc tggcaatgtg gccgtgcagc ccagacgatc
     4141 agagagaagc caggcgttga ccaagcccca aggtgcctga ggccatggtg caactctgct
     4201 ggtgactggg gcaccttgga gcagagcttc acccggatgg gaaatcctca ctcctgggtg
     4261 gcactccctc ctggacaggc ccggtggcag agtgtccgtg ctgctgggtg ctgtccccag
     4321 ccctcctggt ccatcttctt aagatgcgtc cactgcttta tatttaaaat tctctttttc
     4381 acaggcaagg aaaggaaacc actgcttaga gacactaggt acagggcatc aagagggtgc
     4441 agcccagccc cgccaggacg aggcgccgac ttctcattca gggttgacgg agccaagagt
     4501 ttgtgcaaaa tgtatgcatg gtggttgctg ccagcctccc tcatgactaa atgcatatct
     4561 attcctgtca aaacgtgtat cacaatgtac ttgaaactgt tatctttgtg ctctattgtt
     4621 tgaataatta aagaaattac agagactctc
//
