SHH (sonic hedgehog signaling molecule)
- symbol:
- SHH
- locus group:
- protein-coding gene
- location:
- 7q36.3
- gene_family:
- alias symbol:
- HHG1|SMMCI|TPT|TPTPS|MCOPCB5
- alias name:
- None
- entrez id:
- 6469
- ensembl gene id:
- ENSG00000164690
- ucsc gene id:
- uc003wmk.2
- refseq accession:
- NM_000193
- hgnc_id:
- HGNC:10848
- approved reserved:
- 1995-03-10
SHH（Sonic Hedgehog）基因属于Hedgehog（刺猬）基因家族，该家族在胚胎发育中起关键作用，包括细胞分化、器官形成和肢体发育。SHH基因编码一种分泌性蛋白（分泌蛋白指细胞释放到外部的蛋白质），作为信号分子调控靶基因表达。其主要作用位点是发育中的神经管（胚胎中形成大脑和脊髓的结构）、四肢芽基（未来发育为四肢的区域）以及多种内脏器官。SHH蛋白通过结合细胞膜上的受体Patched1（PTCH1）解除其对Smoothened（SMO）受体的抑制，激活下游GLI转录因子（调控基因开关的蛋白质），进而控制细胞增殖和分化。SHH基因突变会导致功能异常，例如功能丧失突变可能引起全前脑畸形（HPE，一种大脑分裂障碍）、多指/趾畸形（额外的手指或脚趾）或骨骼发育异常；而功能获得性突变可能与基底细胞癌（一种皮肤癌）和髓母细胞瘤（儿童脑瘤）相关。SHH过表达会异常激活下游信号通路，导致组织过度生长或肿瘤发生，如戈林综合征（Gorlin syndrome，一种易患癌症的遗传病）；表达不足则引发发育缺陷如HPE或四肢畸形。该基因家族（Hedgehog）的共性是通过保守的信号通路调控形态发生（生物体形状的形成过程），成员包括DHH（Desert Hedgehog）和IHH（Indian Hedgehog），分别参与睾丸和骨骼发育。SHH的表达水平变化还会影响其他基因如PTCH1和GLI的表达，形成反馈调节环路（一种自我平衡机制）。目前SHH抑制剂如vismodegib被用于治疗基底细胞癌，体现其临床重要性。术语补充：形态发生（morphogenesis）、转录因子（transcription factor）、分泌蛋白（secreted protein）、反馈调节（feedback regulation）。
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]
该基因编码的蛋白是在构图早期胚胎的工具。它已被暗示为在腹侧神经管，前 - 后肢轴的图案的关键感应式信号，及腹侧体节。三个人类蛋白质表示序列和功能相似于果蝇的音猬蛋白，这种蛋白是最相似的。该蛋白质是由作为被自催化裂解的前体;的N端部分是可溶的并且含有信号活动而C端部分是参与前体的处理。更重要的是，C末端产物共价附着胆固醇部分的N末端产物，限制N末端产物到细胞表面，并防止它在整个发育中的胚胎自由扩散。在该蛋白质或它的信号传导途径的缺陷是holoprosencephaly（HPE）的一个原因，其中所述显影前脑不能正确分离成左右半球的病症。 HPE是由面部畸形表现。它也被认为是在该基因或在其信号传导途径的突变可以负责VACTERL综合症，其特征是脊椎缺陷，肛门闭锁，气管食管瘘用食管闭锁，径向和肾发育不良，心脏异常，和肢体异常。此外，在很长的范围增强剂突变位于约1兆碱基此基因的上游扰乱肢图案形成，并可能导致preaxial趾。 [由RefSeq的，2008年7月提供]
基因本体信息
SHH基因（以及对应的蛋白质）的细胞分布位置：
- 质膜
- 细胞质
- 细胞外
- 高尔基体
- 囊泡
- 细胞骨架
- 内质网
- 细胞核
- 内体
- 溶酶体
- 线粒体
SHH基因的本体（GO）信息：
| 名称 |
|---|
| 4340 Hedgehog signaling pathway [PATH:hsa04340] |
| 5200 Pathways in cancer [PATH:hsa05200] |
| 5217 Basal cell carcinoma [PATH:hsa05217] |
| 名称 |
|---|
| Activation of SMO |
| Class B/2 (Secretin family receptors) |
| Disease |
| Diseases of signal transduction |
| GPCR ligand binding |
| Hedgehog 'on' state |
| Hedgehog ligand biogenesis |
| Hh mutants abrogate ligand secretion |
| Hh mutants that don't undergo autocatalytic processing are degraded by ERAD |
| Ligand-receptor interactions |
| Release of Hh-Np from the secreting cell |
| Signaling by GPCR |
| Signaling by Hedgehog |
| 疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
| SOLITARY MEDIAN MAXILLARY CENTRAL INCISOR | 0.480814326 | 3 | 3 | BeFree_CLINVAR_CTD_human_ORPHANET_UNIPROT |
| HOLOPROSENCEPHALY 3 | 0.44 | 11 | 26 | CLINVAR_CTD_human_MGD_UNIPROT |
| Congenital ocular coloboma (disorder) | 0.240271442 | 1 | 0 | BeFree_CTD_human_ORPHANET |
| Schizencephaly | 0.240271442 | 1 | 1 | BeFree_CLINVAR_ORPHANET |
| MICROPHTHALMIA, ISOLATED, WITH COLOBOMA 5 (disorder) | 0.24 | 0 | 0 | CLINVAR_CTD_human |
| Holoprosencephaly | 0.154175389 | 69 | 0 | BeFree_CTD_human_GAD_LHGDN |
| Syndactyly, Type IV | 0.120814326 | 3 | 0 | BeFree_ORPHANET |
| POLYDACTYLY, PREAXIAL II (disorder) | 0.120271442 | 1 | 0 | BeFree_CTD_human |
| Semilobar Holoprosencephaly | 0.12 | 0 | 0 | ORPHANET |
| Lobar Holoprosencephaly | 0.12 | 0 | 0 | ORPHANET |
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