Indian hedgehog (protein)

Last updated

IHH
Protein IHH PDB 1vhh.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IHH , BDA1, HHG2, indian hedgehog, Indian hedgehog signaling molecule
External IDs OMIM: 600726; MGI: 96533; HomoloGene: 22586; GeneCards: IHH; OMA:IHH - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002181

NM_010544
NM_001313683

RefSeq (protein)

NP_002172

NP_001300612
NP_034674

Location (UCSC) Chr 2: 219.05 – 219.06 Mb Chr 1: 74.98 – 74.99 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Indian hedgehog homolog (Drosophila), also known as IHH, is a protein which in humans is encoded by the IHH gene. [5] [6] [7] This cell signaling protein is in the hedgehog signaling pathway. The several mammalian variants of the Drosophila hedgehog gene (which was the first named) have been named after the various species of hedgehog; the Indian hedgehog is honored by this one. The gene is not specific to Indian hedgehogs.

Contents

Function

The Indian hedgehog protein is one of three proteins in the mammalian hedgehog family, the others being desert hedgehog (DHH) and sonic hedgehog (SHH). [8] It is involved in chondrocyte differentiation, proliferation and maturation especially during endochondral ossification. It regulates its effects by feedback control of parathyroid hormone-related peptide (PTHrP). [9]

Indian Hedge Hog, (Ihh) is one of three signaling molecules from the Hedgehog (Hh) gene family. [10] Genes of the Hh family, Sonic Hedgehog (Shh), Desert Hedgehog (Dhh) and Ihh regulate several fetal developmental processes. [10] The Ihh homolog is involved in the formation of chondrocytes during the development of limbs. [10] The protein is released by small, non-proliferating, mature chondrocytes during endochondral ossification. [10] Recently, Ihh mutations are shown to cause brachydactyly type A1 (BDA1), the first Mendelian autosomal dominant disorder in humans to be recorded. [10] [11] There are seven known mutations to Ihh that cause BDA1. [11] Of particular interest, are mutations involving the E95 residue, which is thought to be involved with proper signaling mechanisms between Ihh and its receptors. [11] In a mouse model, mice with mutations to the E95 residue were found to have abnormalities to their digits. [12]

Ihh may also be involved in endometrial cell differentiation and implantation. Studies have shown progesterone to upregulate Ihh expression in the murine endometrium, suggesting a role in implantation. [13] Ihh is suspected to be involved in the downstream regulation of other signaling molecules that are known to play a role in murine implantation. [14] Mouse models involving Ihh null mice demonstrated failure of attachment and decidualization. [14]

Related Research Articles

<span class="mw-page-title-main">Sonic hedgehog protein</span> Signaling molecule in animals

Sonic hedgehog protein (SHH) is encoded for by the SHH gene. The protein is named after the video game character Sonic the Hedgehog.

<span class="mw-page-title-main">Parathyroid hormone-related protein</span> Mammalian protein

Parathyroid hormone-related protein (PTHrP) is a proteinaceous hormone and a member of the parathyroid hormone family secreted by mesenchymal stem cells. It is occasionally secreted by cancer cells. However, it also has normal functions in bone, teeth, vascular tissues and other tissues.

<span class="mw-page-title-main">Chondrocyte</span> Cell that composes cartilage

Chondrocytes are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word chondroblast is commonly used to describe an immature chondrocyte, the term is imprecise, since the progenitor of chondrocytes can differentiate into various cell types, including osteoblasts.

<span class="mw-page-title-main">GLI2</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein GLI2 also known as GLI family zinc finger 2 is a protein that in humans is encoded by the GLI2 gene. The protein encoded by this gene is a transcription factor.

<span class="mw-page-title-main">GLI3</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein GLI3 is a protein that in humans is encoded by the GLI3 gene.

<span class="mw-page-title-main">Chondrogenesis</span>

Chondrogenesis is the biological process through which cartilage tissue is formed and developed. This intricate and tightly regulated cellular differentiation pathway plays a crucial role in skeletal development, as cartilage serves as a fundamental component of the embryonic skeleton. The term "chondrogenesis" is derived from the Greek words "chondros," meaning cartilage, and "genesis," meaning origin or formation.

The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathway also has roles in the adult. Diseases associated with the malfunction of this pathway include cancer.

<span class="mw-page-title-main">ROR2</span> Protein

Tyrosine-protein kinase transmembrane receptor ROR2, also known as neurotrophic tyrosine kinase, receptor-related 2, is a protein that in humans is encoded by the ROR2 gene located on position 9 of the long arm of chromosome 9. This protein is responsible for aspects of bone and cartilage growth. It is involved in Robinow syndrome and autosomal dominant brachydactyly type B. ROR2 is a member of the receptor tyrosine kinase-like orphan receptor (ROR) family.

<span class="mw-page-title-main">Smoothened</span> Gene found in humans and other animals

Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA).

<span class="mw-page-title-main">Bone morphogenetic protein 6</span> Protein-coding gene in the species Homo sapiens

Bone morphogenetic protein 6 is a protein that in humans is encoded by the BMP6 gene.

<span class="mw-page-title-main">GDF5</span> Protein-coding gene in the species Homo sapiens

Growth/differentiation factor 5 is a protein that in humans is encoded by the GDF5 gene.

Limbin (LBN) is a protein that is part of the EvC complex that consists of EvC and EvC2 genes, the activity of which is critical in bone formation and skeletal development. The complex positively regulates ciliary Hedgehog (Hh) signaling due to the ciliary localization.

<span class="mw-page-title-main">Notch 4</span> Protein-coding gene in the species Homo sapiens

Neurogenic locus notch homolog 4(Notch 4) is a protein that in humans is encoded by the NOTCH4 gene located on chromosome 6.

<span class="mw-page-title-main">PTCH1</span> Protein-coding gene in the species Homo sapiens

Protein patched homolog 1 is a protein that is the member of the patched family and in humans is encoded by the PTCH1 gene.

<span class="mw-page-title-main">Eyes absent homolog 1</span> Protein-coding gene in the species Homo sapiens

Eyes absent homolog 1 is a protein that in humans is encoded by the EYA1 gene.

<span class="mw-page-title-main">DLX3</span> Mammalian protein found in Homo sapiens

Homeobox protein DLX-3 is a protein that in humans is encoded by the DLX3 gene.

<span class="mw-page-title-main">SUFU</span> Protein-coding gene in the species Homo sapiens

Suppressor of fused homolog is a protein that in humans is encoded by the SUFU gene. In molecular biology, the protein domain suppressor of fused protein (Sufu) has an important role in the cell. The Sufu is important in negatively regulating an important signalling pathway in the cell, the Hedgehog signalling pathway (HH). This particular pathway is crucial in embryonic development. There are several homologues of Sufu, found in a wide variety of organisms.

<span class="mw-page-title-main">FOXE1</span> Mammalian protein found in Homo sapiens

Forkhead box protein E1 is a protein that in humans is encoded by the FOXE1 gene.

<span class="mw-page-title-main">HHIP</span> Protein-coding gene in the species Homo sapiens

Hedgehog interacting protein (HHIP) is a protein that in humans is encoded by the HHIP gene.

<span class="mw-page-title-main">RAB23</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rab-23 is a protein that in humans is encoded by the RAB23 gene. Alternative splicing occurs at this gene locus and two transcript variants encoding the same protein have been identified.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000163501 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000006538 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: IHH Indian hedgehog homolog (Drosophila)".
  6. Marigo V, Roberts DJ, Lee SM, Tsukurov O, Levi T, Gastier JM, Epstein DJ, Gilbert DJ, Copeland NG, Seidman CE (July 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.
  7. van den Brink GR, Bleuming SA, Hardwick JC, Schepman BL, Offerhaus GJ, Keller JJ, Nielsen C, Gaffield W, van Deventer SJ, Roberts DJ, Peppelenbosch MP (March 2004). "Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation". Nat. Genet. 36 (3): 277–82. doi: 10.1038/ng1304 . PMID   14770182.
  8. Kumar S, Balczarek KA, Lai ZC (March 1996). "Evolution of the hedgehog gene family". Genetics. 142 (3): 965–72. doi:10.1093/genetics/142.3.965. PMC   1207033 . PMID   8849902.
  9. Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ (August 1996). "Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein". Science. 273 (5275): 613–22. Bibcode:1996Sci...273..613V. doi:10.1126/science.273.5275.613. PMID   8662546. S2CID   27737023.
  10. 1 2 3 4 5 Ma, G., Yu, J., Xiao, Y. et al. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels. Cell Res 21, 1343–1357 (2011). https://doi.org/10.1038/cr.2011.76
  11. 1 2 3 Lodder EM, Hoogeboom AJM, Coert JH, de Graaff E. 2008. Deletion of 1 amino acid in Indian hedgehog leads to brachydactylyA1. Am J Med Genet Part A 146A:2152–2154. doi:10.1002/ajmg.a.32441
  12. Gao, B., Hu, J., Stricker, S. et al. A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range. Nature 458, 1196–1200 (2009). https://doi.org/10.1038/nature07862
  13. Qingxiang Wei, Eric D. Levens, Lilja Stefansson, Lynnette K. Nieman, Indian Hedgehog and Its Targets in Human Endometrium: Menstrual Cycle Expression and Response to CDB-2914, The Journal of Clinical Endocrinology & Metabolism, Volume 95, Issue 12, 1 December 2010, Pages 5330–5337, https://doi.org/10.1210/jc.2010-0637
  14. 1 2 Kathryn Smith, Redab Alnifaidy, Qingxiang Wei, Lynnette K. Nieman, Endometrial Indian hedgehog expression is decreased in women with endometriosis, Fertility and Sterility, Volume 95, Issue 8, 2011, Pages 2738-2741.e3, ISSN 0015-0282, https://doi.org/10.1016/j.fertnstert.2011.05.018.

Further reading