Grainy head gene transcriptions

Associate Editor(s)-in-Chief: Henry A. Hoff

"The defined GRHL1 DNA‐binding consensus sequence (AACCGGTT) was identical to that defined for GRHL3, and also matched the consensus sequence for Drosophila GRH DNA binding, which we had previously identified by alignment of multiple GRH‐responsive gene regulatory regions (Wilanowski et al, 2002; Ting et al, 2005). Of note, the first of the two cytosines and the second of the guanines were invariant in both GRHL1 and GRHL3 CASTing assays."

"The putative GRHL1‐binding motif (GACTGGTT) is perfectly conserved, together with 6 bp upstream and 12 bp downstream flanking sequences, in three of the Dsg1 promoters: mouse Dsg1α, mouse Dsg1γ, and human DSG1 [...]. In the mouse Dsg1β promoter, this motif is slightly different (AACTGGTT), although the flanking sequences are still conserved."

"The consensus DNA‐binding sequence identified for GRHL1 is identical to that defined for Drosophila GRH (Wilanowski et al, 2002). In addition, the identification of cadherin genes as direct transcriptional targets of GRHL1 extends the links between the grh and cadherin gene families from Drosophila to mammals. The cadherin family consists of more than 100 members (including the protocadherins) involved in many diverse cellular and developmental events (Nollet et al, 2000). Among the known targets of Drosophila, GRH are two cadherin superfamily members, stan/fmi and E‐cadherin/shotgun (Lee and Adler, 2004; Almeida and Bray, 2005). The links between the two gene families have recently been extended in another model organism. A study of genome‐wide predictions of genetic interactions in C. elegans has identified a number of cadherin family members as prime targets for significant functional interactions with Grh‐1, the worm homologue of grh (Zhong and Sternberg, 2006). These included cdh‐6, a homologue of Drosophila stan, and hmp‐2, a β‐catenin. We have recently identified the mammalian homologue of E‐cadherin as a target of another member of the Grh‐like family, Grhl2 (JMC and SMJ, unpublished)."

Human genes

Cadherin genes

Gene ID: 999 is CDH1 cadherin 1: "This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid and ovarian cancer. Loss of function of this gene is thought to contribute to cancer progression by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells and the cytoplasmic domain is required for internalization. This gene is present in a gene cluster with other members of the cadherin family on chromosome 16."

1. NP_001304113.1 cadherin-1 isoform 2 precursor: "Transcript Variant: This variant (2) lacks an alternate exon in the central coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform 1."
2. NP_001304114.1 cadherin-1 isoform 3: "Transcript Variant: This variant (3) uses an alternate splice site in an exon in its 5' UTR, resulting in a different 5' UTR and the use of a downstream start site compared to variant 1. The encoded isoform (3) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1."
3. NP_001304115.1 cadherin-1 isoform 4: "Transcript Variant: This variant (4) lacks an exon in its 5' UTR, resulting in a different 5' UTR and the use of a downstream start site compared to variant 1. The encoded isoform (4) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1."
4. NP_004351.1 cadherin-1 isoform 1 preproprotein: "Transcript Variant: This variant (1) encodes the longest isoform (1)."

Gene ID: 1000 is CDH2 cadherin 2: "This gene encodes a classical cadherin and member of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein is proteolytically processed to generate a calcium-dependent cell adhesion molecule and glycoprotein. This protein plays a role in the establishment of left-right asymmetry, development of the nervous system and the formation of cartilage and bone."

1. NP_001295105.1 cadherin-2 isoform 2: "Transcript Variant: This variant (2) represents use of an alternate promoter, and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at an alternate start codon, resulting in an isoform (2) that lacks a predicted signal peptide and has a distinct N-terminus compared to isoform 1."
2. NP_001783.2 cadherin-2 isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."

Gene ID: 1001 is CDH3 cadherin 3: "This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS)."

1. NP_001304124.1 cadherin-3 isoform 2 precursor: "Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, which results in a frameshift and an early stop codon. The encoded isoform (2) has a shorter and distinct C-terminus compared to isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform (1)."
2. NP_001304125.1 cadherin-3 isoform 3: "Transcript Variant: This variant (3) lacks an alternate exon in its 5' UTR, resulting in the use of a downstream translation start site compared to variant 1. The encoded isoform (3) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1."
3. NP_001784.2 cadherin-3 isoform 1 preproprotein": "Transcript Variant: This variant (1) encodes the longest isoform (1)."

Gene ID: 1002 is CDH4 cadherin 4: "This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene."

1. NP_001239267.1 cadherin-4 isoform 2: "Transcript Variant: This variant (2) has an alternate exon in place of the first two exons compared to variant 1, and the alternate exon has an in-frame translation start site. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1."
2. NP_001239268.1 cadherin-4 isoform 3: "Transcript Variant: This variant (3) has an alternate exon in place of the first two exons compared to variant 1, but the alternate exon does not have an in-frame translation start site. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1."
3. NP_001785.2 cadherin-4 isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."

Gene ID: 1003 is CDH5 cadherin 5: "This gene encodes a classical cadherin of the cadherin superfamily. The encoded preproprotein is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Functioning as a classical cadherin by imparting to cells the ability to adhere in a homophilic manner, this protein plays a role in endothelial adherens junction assembly and maintenance. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer."

Gene ID: 1004 is CDH6 cadherin 6: "This gene encodes a member of the cadherin superfamily. Cadherins are membrane glycoproteins that mediate homophilic cell-cell adhesion and play critical roles in cell differentiation and morphogenesis. The encoded protein is a type II cadherin and may play a role in kidney development as well as endometrium and placenta formation. Decreased expression of this gene may be associated with tumor growth and metastasis."

1. NP_001349364.1 cadherin-6 isoform 2 preproprotein: "Transcript Variant: This variant (2) differs in the 3' CDS and 3' UTR, compared to variant 1, and encodes a protein (isoform 2) with a shorter and distinct C-terminus, compared to isoform 1."
2. NP_004923.1 cadherin-6 isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."

Gene ID: 1005 is CDH7 cadherin 7: "This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium dependent cell-cell adhesion molecule is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. Cadherins mediate cell-cell binding in a homophilic manner, contributing to the sorting of heterogeneous cell types. Mutations in this gene may be associated with bipolar disease in human patients. This gene is present in a gene cluster on chromosome 18."

1. NP_001304143.1 cadherin-7 isoform 2 precursor: "Transcript Variant: This variant (c) lacks several exons and its 3' terminal exon extends past a splice site that is used in variant b. This results in a novel 3' coding region and 3' UTR, compared to variant b. The encoded isoform has a shorter and distinct C-terminus compared to isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform 1."
2. NP_001349367.1 cadherin-7 isoform 1 preproprotein: "Transcript Variant: This variant (d) differs in the 5' UTR compared to variant b. Variants a, b and d encode the same isoform (1)."
3. NP_004352.2 cadherin-7 isoform 1 preproprotein: "Transcript Variant: This variant (b) represents the longest transcript and encodes the longer isoform (1). Variants a, b and d encode the same isoform (1)."
4. NP_387450.1 cadherin-7 isoform 1 preproprotein: "Transcript Variant: This variant (a) differs in the 5' UTR compared to variant b. Variants a, b and d encode the same isoform (1)."

Gene ID: 1006 is CDH8 cadherin 8: "This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed in brain and is putatively involved in synaptic adhesion, axon outgrowth and guidance."

Gene ID: 1007 is CDH9 cadherin 9: "This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins."

1. NP_057363.3 cadherin-9 preproprotein.

Gene ID: 1008 is CDH10 cadherin 10: "This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is predominantly expressed in brain and is putatively involved in synaptic adhesions, axon outgrowth and guidance. Mutations in this gene may be associated with lung squamous cell carcinoma and colorectal cancer in human patients."

1. NP_001304151.1 cadherin-10 isoform 2: "Transcript Variant: This variant (2) differs in the 5' UTR and uses a downstream translation start site compared to variant 1. The encoded isoform (2) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1."
2. NP_001304153.1 cadherin-10 isoform 3 preproprotein: "Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The encoded isoform (3, also known as CDH10_B) is shorter than isoform 1. This isoform (3) may undergo proteolytic processing similar to isoform 1."
3. NP_001349389.1 cadherin-10 isoform 4 preproprotein: "Transcript Variant: This variant (4) lacks two in-frame exons in the 3' coding region compared to variant 1. The encoded isoform (4) is shorter than isoform 1. This isoform (4) may undergo proteolytic processing similar to isoform 1."
4. NP_006718.2 cadherin-10 isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."

Gene ID: 1009 is CDH11 cadherin 11: "This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Expression of this particular cadherin in osteoblastic cell lines, and its upregulation during differentiation, suggests a specific function in bone development and maintenance."

1. NP_001295321.1 cadherin-11 isoform 2 precursor: "Transcript Variant: This variant (2) uses an alternate exon in the 3' coding region which results in a frameshift compared to variant 1. The encoded isoform (2) has a shorter C-terminus compared to isoform 1."
2. NP_001317505.1 cadherin-11 isoform 3: "Transcript Variant: This variant (3) lacks an alternate exon, resulting in a distinct 5' UTR and the use of a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus compared to isoform 1."
3. NP_001788.2 cadherin-11 isoform 1 preproprotein: "Transcript Variant: This variant (1) encodes the longer isoform (1)."

Gene ID: 1010 is CDH12 cadherin 12: "This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin appears to be expressed specifically in the brain and its temporal pattern of expression would be consistent with a role during a critical period of neuronal development, perhaps specifically during synaptogenesis."

1. NP_001304156.1 cadherin-12 isoform 1 preproprotein: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 4-8 all encode the same isoform (1)."
2. NP_001304157.1 cadherin-12 isoform 2 precursor: "Transcript Variant: This variant (3) differs in the 5' UTR and lacks an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform 1."
3. NP_001351033.1 cadherin-12 isoform 1 preproprotein: "Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 4-8 all encode the same isoform (1)."
4. NP_001351034.1 cadherin-12 isoform 1 preproprotein: "Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 4-8 all encode the same isoform (1)."
5. NP_001351035.1 cadherin-12 isoform 1 preproprotein: "Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 4-8 all encode the same isoform (1)."
6. NP_001351036.1 cadherin-12 isoform 1 preproprotein: "Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 4-8 all encode the same isoform (1)."
7. NP_001351037.1 cadherin-12 isoform 1 preproprotein: "Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 4-8 all encode the same isoform (1)."
8. NP_001351038.1 cadherin-12 isoform 3: "Transcript Variant: This variant (9) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1."
9. NP_004052.2 cadherin-12 isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). Variants 1, 2, and 4-8 all encode the same isoform (1)."

Gene ID: 1012 is CDH13 cadherin 13: "This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms."

1. NP_001207417.1 cadherin-13 isoform 2: "Transcript Variant: This variant (2) includes an alternate exon in the 5' coding region, compared to variant 1. It encodes isoform 2, which is longer and has a distinct N-terminus, compared to isoform 1."
2. NP_001207418.1 cadherin-13 isoform 3 precursor: "Transcript Variant: This variant (3) lacks an in-frame exon in the coding region, compared to variant 1. It encodes isoform 3, which is shorter than isoform 1."
3. NP_001207419.1 cadherin-13 isoform 4: "Transcript Variant: This variant (4) lacks an exon in the coding region resulting in use of a downstream start codon, compared to variant 1. It encodes isoform 4, which is shorter and has a distinct N-terminus, compared to isoform 1."
4. NP_001207420.1 cadherin-13 isoform 5 precursor: "Transcript Variant: This variant (5) lacks several coding exons and uses an alternate 3' terminal exon, compared to variant 1. It encodes isoform 5, which is shorter and has a distinct C-terminus, compared to isoform 1."
5. NP_001207421.1 cadherin-13 isoform 6 precursor: "Transcript Variant: This variant (6) lacks several coding exons and includes two alternate exons at the 3' end, compared to variant 1. It encodes isoform 6, which is shorter and has a distinct C-terminus, compared to isoform 1."
6. NP_001248.1 cadherin-13 isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the predominant transcript and encodes isoform 1."

Desmoglein genes

Gene ID: 1828 is DSG1 desmoglein 1: "This gene encodes a member of the desmoglein protein subfamily. Desmogleins, along with desmocollins, are cadherin-like transmembrane glycoproteins that are major components of the desmosome. Desmosomes are cell-cell junctions that help resist shearing forces and are found in high concentrations in cells subject to mechanical stress. This gene is found in a cluster with other desmoglein family members on chromosome 18. The encoded protein has been identified as a target of auto-antibodies in the autoimmune skin blistering disease pemphigus foliaceus. Disruption of this gene has also been associated with the skin diseases palmoplantar keratoderma and erythroderma."

See also

• Cadherin
• Transcription factor