Mothers against decapentaplegic homolog 1

SMAD1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1KHU, 2LAW, 2LAX, 2LAY, 2LAZ, 2LB0, 2LB1, 3Q47, 3Q4A Contents Nomenclature ; Function ; References ; External links ;
Identifiers
Aliases	SMAD1 , BSP-1, BSP1, JV4-1, JV41, MADH1, MADR1, SMAD family member 1
External IDs	OMIM: 601595 MGI: 109452 HomoloGene: 21196 GeneCards: SMAD1
Gene location (Mouse)
Chr.	Chromosome 8 (mouse) [1]
End	79,399,518 bp [1]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• DNA binding ; • co-SMAD binding ; • protein homodimerization activity ; • I-SMAD binding ; • transcription factor activity, sequence-specific DNA binding ; • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding ; • metal ion binding ; • transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity ; • protein binding ; • identical protein binding ; • protein heterodimerization activity ; • protein kinase binding ; • sequence-specific DNA binding ; • DEAD/H-box RNA helicase binding ; • primary miRNA binding ; • RNA polymerase II core promoter proximal region sequence-specific DNA binding ; • RNA polymerase II transcription factor activity, sequence-specific DNA binding ;
Cellular component	• cytoplasm ; • integral component of membrane ; • SMAD protein complex ; • cytosol ; • transcription factor complex ; • intracellular ; • nucleoplasm ; • nuclear inner membrane ; • cell nucleus ; • macromolecular complex ;
Biological process	• positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus ; • SMAD protein complex assembly ; • ureteric bud development ; • regulation of transcription, DNA-templated ; • SMAD protein signal transduction ; • embryonic pattern specification ; • regulation of transcription from RNA polymerase II promoter ; • cellular response to organic cyclic compound ; • hindbrain development ; • cellular response to BMP stimulus ; • cardiac muscle cell proliferation ; • BMP signaling pathway ; • transcription, DNA-templated ; • MAPK cascade ; • protein phosphorylation ; • gamete generation ; • cartilage development ; • positive regulation of gene expression ; • positive regulation of osteoblast differentiation ; • positive regulation of cartilage development ; • primary miRNA processing ; • mesodermal cell fate commitment ; • inflammatory response ; • bone development ; • transforming growth factor beta receptor signaling pathway ; • midbrain development ; • signal transduction ; • negative regulation of cell proliferation ; • positive regulation of transcription from RNA polymerase II promoter ; • osteoblast fate commitment ; • homeostatic process ; • transcription from RNA polymerase II promoter ; • positive regulation of pri-miRNA transcription from RNA polymerase II promoter ; • protein deubiquitination ; • positive regulation of sprouting angiogenesis ;
	Sources:Amigo / QuickGO
Orthologs
	4086
	17125
	n/a
	ENSMUSG00000031681
	Q15797
	P70340
	NM_001003688 ; NM_005900
	NM_008539
NP_001003688 ; NP_005891 ; NP_001341740 ; NP_001341741 ; NP_001341742 ;
	NP_001341743 ; NP_001341745 ; NP_001341746
	NP_032565
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated April 25, 2019

Mothers against decapentaplegic homolog 1 also known as SMAD family member 1 or SMAD1 is a protein that in humans is encoded by the SMAD1 gene.^[4]^[5]

Protein biological molecule consisting of chains of amino acid residues

Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.

In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

Nomenclature

SMAD1 belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma.^{[ citation needed ]} The name is a combination of the two; and based on a tradition of such unusual naming within the gene research community.^[6]

Smads comprise a family of structurally similar proteins that are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily, which are critically important for regulating cell development and growth. The abbreviation refers to the homologies to the Caenorhabditis elegans SMA and Drosophila MAD family of genes.

Drosophila is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit. They should not be confused with the Tephritidae, a related family, which are also called fruit flies ; tephritids feed primarily on unripe or ripe fruit, with many species being regarded as destructive agricultural pests, especially the Mediterranean fruit fly. One species of Drosophila in particular, D. melanogaster, has been heavily used in research in genetics and is a common model organism in developmental biology. The terms "fruit fly" and "Drosophila" are often used synonymously with D. melanogaster in modern biological literature. The entire genus, however, contains more than 1,500 species and is very diverse in appearance, behavior, and breeding habitat.

Mothers against decapentaplegic is a protein from the SMAD family that was discovered in Drosophila. During Drosophila research, it was found that a mutation in the gene in the mother repressed the gene decapentaplegic in the embryo. The phrase "Mothers against" was added as a humorous take-off on organizations opposing various issues e.g. Mothers Against Drunk Driving (MADD); and based on a tradition of such unusual naming within the gene research community.

It was found that a mutation in the 'Drosophila' gene, MAD, in the mother, repressed the gene, decapentaplegic , in the embryo. Mad mutations can be placed in an allelic series based on the relative severity of the maternal effect enhancement of weak dpp alleles, thus explaining the name Mothers against dpp.^[7]

Decapentaplegic (Dpp) is a key morphogen involved in the development of the fruit fly Drosophila melanogaster and is the first validated secreted morphogen. It is known to be necessary for the correct patterning and development of the early Drosophila embryo and the fifteen imaginal discs, which are tissues that will become limbs and other organs and structures in the adult fly. It has also been suggested that Dpp plays a role in regulating the growth and size of tissues. Flies with mutations in decapentaplegic fail to form these structures correctly, hence the name. Dpp is the Drosophila homolog of the vertebrate bone morphogenetic proteins (BMPs), which are members of the TGF-β superfamily, a class of proteins that are often associated with their own specific signaling pathway. Studies of Dpp in Drosophila have led to greater understanding of the function and importance of their homologs in vertebrates like humans.

Function

SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signals of the bone morphogenetic proteins (BMPs), which are involved in a range of biological activities including cell growth, apoptosis, morphogenesis, development and immune responses. In response to BMP ligands, this protein can be phosphorylated and activated by the BMP receptor kinase. The phosphorylated form of this protein forms a complex with SMAD4, which is important for its function in the transcription regulation. This protein is a target for SMAD-specific E3 ubiquitin ligases, such as SMURF1 and SMURF2, and undergoes ubiquitination and proteasome-mediated degradation. Alternatively spliced transcript variants encoding the same protein have been observed.^[8]

Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. The important functioning of BMP signals in physiology is emphasized by the multitude of roles for dysregulated BMP signalling in pathological processes. Cancerous disease often involves misregulation of the BMP signalling system. Absence of BMP signalling is, for instance, an important factor in the progression of colon cancer, and conversely, overactivation of BMP signalling following reflux-induced esophagitis provokes Barrett's esophagus and is thus instrumental in the development of adenocarcinoma in the proximal portion of the gastrointestinal tract.

Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between the ages of 8 to 14 year old approximately 20 to 30 billion cells die per day.

Morphogenesis is the biological process that causes an organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of cell growth and cellular differentiation, unified in evolutionary developmental biology (evo-devo).

SMAD1 is a receptor regulated SMAD (R-SMAD) and is activated by bone morphogenetic protein type 1 receptor kinase.

R-SMADs are receptor-regulated SMADs. SMADs are transcription factors that transduce extracellular TGF-β superfamily ligand signaling from cell membrane bound TGF-β receptors into the nucleus where they activate transcription TGF-β target genes. R-SMADS are directly phosphorylated on their c-terminus by type 1 TGF-β receptors through their intracellular kinase domain, leading to r-SMAD activation.

Related Research Articles

Paracrine signaling is a form of cell-to-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance, as opposed to endocrine factors, juxtacrine interactions, and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

The JAK-STAT signalling pathway is a chain of interactions between proteins in a cell, and is involved in processes such as immunity, cell division, cell death and tumour formation. The pathway communicates information from chemical signals outside of a cell to the cell nucleus, resulting in the activation of genes through a process called transcription. There are three key parts of JAK-STAT signalling: Janus kinases (JAKs), Signal Transducer and Activator of Transcription proteins (STATs), and receptors. Disrupted JAK-STAT signalling may lead to a variety of diseases, such as skin conditions, cancers, and disorders affecting the immune system.

Bone morphogenetic protein 4 is a protein that in humans is encoded by BMP4 gene. BMP4 is found on chromosome 14q22-q23

Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the SMAD2 gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways.

Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.

SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 is a highly-conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, which act as mediators of TGF-β signal transduction. The TGFβ family of cytokines regulates critical processes during the lifecycle of metazoans, with important roles during embryo development, tissue homeostasis, regeneration, and immune regulation.

SMAD family member 6, also known as SMAD6, is a protein that in humans is encoded by the SMAD6 gene.

Mothers against decapentaplegic homolog 5 also known as SMAD5 is a protein that in humans is encoded by the SMAD5 gene.

Mothers against decapentaplegic homolog 7 or SMAD7 is a protein that in humans is encoded by the SMAD7 gene.

Mothers against decapentaplegic homolog 9 also known as SMAD9, SMAD8, and MADH6 is a protein that in humans is enocoded by the SMAD9 gene.

The transforming growth factor beta (TGFB) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. In spite of the wide range of cellular processes that the TGFβ signaling pathway regulates, the process is relatively simple. TGFβ superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor. The type I receptor then phosphorylates receptor-regulated SMADs (R-SMADs) which can now bind the coSMAD SMAD4. R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression.

Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic proteins, members of the TGF beta superfamily of ligands, which are involved in paracrine signalling. BMPs are involved in a host of cellular functions including osteogenesis, cell growth and cell differentiation. Signaling in the BMP pathway begins with the binding of a BMP to the type II receptor. This causes the recruitment of a BMP type I receptor, which it phosphorylates. The Type I receptor phosphorylates an R-SMAD a transcriptional regulator.

The bone morphogenetic protein receptor, type IA also known as BMPR1A is a protein which in humans is encoded by the BMPR1A gene. BMPR1A has also been designated as CD292.

Activin A receptor, type I (ACVR1) is a protein which in humans is encoded by the ACVR1 gene; also known as ALK-2. ACVR1 has been linked to the 2q23-24 region of the genome. This protein is important in the bone morphogenic protein (BMP) pathway which is responsible for the development and repair of the skeletal system. While knock-out models with this gene are in progress, the ACVR1 gene has been connected to Fibrodysplasia Ossificans Progressiva, a disease characterized by the formation of heterotopic bone throughout the body. It is a Bone morphogenetic protein receptor, type 1.

Growth differentiation factor 2 (GDF2) also known as bone morphogenetic protein (BMP)-9 is a protein that in humans is encoded by the GDF2 gene. GDF2 belongs to the transforming growth factor beta superfamily.

Bone morphogenetic protein receptor type-1B also known as CDw293 is a protein that in humans is encoded by the BMPR1B gene.

Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the MAP3K7 gene.

References

1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031681 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Hoodless PA, Haerry T, Abdollah S, Stapleton M, O'Connor MB, Attisano L, Wrana JL (May 1996). "MADR1, a MAD-related protein that functions in BMP2 signaling pathways". Cell. 85 (4): 489–500. doi:10.1016/S0092-8674(00)81250-7. PMID 8653785.
↑ Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B (July 1996). "Mad-related genes in the human". Nature Genetics. 13 (3): 347–9. doi:10.1038/ng0796-347. PMID 8673135.
↑ "Sonic Hedgehog, DICER, and the Problem With Naming Genes", Sep 26, 2014, Michael White. psmag.com
↑ "Interactive fly, Drosophila".
↑ "Entrez Gene: SMAD1 SMAD family member 1".

External links

DrosophilaMothers against dpp - The Interactive Fly
Smad1 Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
SMAD1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

Medical Subject Headings (MeSH) is a comprehensive controlled vocabulary for the purpose of indexing journal articles and books in the life sciences. It serves as a thesaurus that facilitates searching. Created and updated by the United States National Library of Medicine (NLM), it is used by the MEDLINE/PubMed article database and by NLM's catalog of book holdings. MeSH is also used by ClinicalTrials.gov registry to classify which diseases are studied by trials registered in ClinicalTrials.

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[refGRCm38Ensembl-1] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031681 - Ensembl, May 2017

[2] "Human PubMed Reference:".

[3] "Mouse PubMed Reference:".

[pmid8653785-4] Hoodless PA, Haerry T, Abdollah S, Stapleton M, O'Connor MB, Attisano L, Wrana JL (May 1996). "MADR1, a MAD-related protein that functions in BMP2 signaling pathways". Cell. 85 (4): 489–500. doi:10.1016/S0092-8674(00)81250-7. PMID 8653785.

[pmid8673135-5] Riggins GJ, Thiagalingam S, Rozenblum E, Weinstein CL, Kern SE, Hamilton SR, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B (July 1996). "Mad-related genes in the human". Nature Genetics. 13 (3): 347–9. doi:10.1038/ng0796-347. PMID 8673135.

[6] "Sonic Hedgehog, DICER, and the Problem With Naming Genes", Sep 26, 2014, Michael White. psmag.com

[7] "Interactive fly, Drosophila".

[8] "Entrez Gene: SMAD1 SMAD family member 1".