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the mammalian homologue of E‐cadherin as a target of another member of the Grh‐like family, Grhl2 (JMC and SMJ, unpublished)."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

Grainy head genes

Gene ID: 29841 is GRHL1 grainyhead like transcription factor 1: "This gene encodes a member of the grainyhead family of transcription factors. The encoded protein can exist as a homodimer or can form heterodimers with sister-of-mammalian grainyhead or brother-of-mammalian grainyhead. This protein functions as a transcription factor during development."

1. NP_937825.2 grainyhead-like protein 1 homolog.

Gene ID: 57822 is GRHL3 grainyhead like transcription factor 3: "This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene."

1. NP_001181939.1 grainyhead-like protein 3 homolog isoform 4: "Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (4) is shorter than isoform 1."
2. NP_067003.2 grainyhead-like protein 3 homolog isoform 1: "Transcript Variant: This variant (1, also known as SOM1) encodes isoform 1."
3. NP_937816.1 grainyhead-like protein 3 homolog isoform 2: "Transcript Variant: This variant (2, also known as SOM2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1."
4. NP_937817.3 grainyhead-like protein 3 homolog isoform 3: "Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. This variant also differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (3) has distinct N- and C-termini and is longer than isoform 1."

Gene ID: 79977 is GRHL2 grainyhead like transcription factor 2: "The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28)."

1. NP_001317522.1 grainyhead-like protein 2 homolog isoform 2.
2. NP_079191.2 grainyhead-like protein 2 homolog isoform 1.

Protocadherins

Gene ID: 5097 is PCDH1 protocadherin 1: "This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene."

1. NP_001265542.1 protocadherin-1 isoform 3: "Transcript Variant: This variant (3) has an alternate 5' exon and lacks two 3' exons. Its transcription extends past a splice site that is used in variant 2, resulting in a novel 3' coding region and 3' UTR compared to variant 2. It encodes isoform 3 which is shorter and has a distinct C-terminus, compared to isoform 2."
2. NP_001265544.1 protocadherin-1 isoform 4: "Transcript Variant: This variant (4) lacks two 5' and 3' exons, respectively. It has an alternate 5' exon and its transcription extends past a splice site that is used in variant 2, resulting in a novel 3' coding region and 3' UTR compared to variant 2. It encodes isoform 4 which has a shorter N-terminus and a shorter and distinct C-terminus, compared to isoform 2."
3. NP_002578.2 protocadherin-1 isoform 1 precursor: "Transcript Variant: This variant (1) lacks two exons and its transcription extends past a splice site that is used in variant 2, resulting in a novel 3' coding region and 3' UTR compared to variant 2. It encodes isoform 1 which is shorter and has a distinct C-terminus, compared to isoform 2."
4. NP_115796.2 protocadherin-1 isoform 2 precursor: "Transcript Variant: This variant (2) represents the longest transcript and encodes the longest isoform (2)."

Gene ID: 27328 is PCDH11X protocadherin 11 X-linked: "This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia. Alternative splicing results in multiple transcript variants."

1. NP_001161832.1 protocadherin-11 X-linked isoform e precursor: "Transcript Variant: This variant (e) lacks an in-frame exon in the 3' coding region, compared to variant c. The encoded isoform (e) is shorter, compared to isoform c."
2. NP_001161833.1 protocadherin-11 X-linked isoform f precursor: "Transcript Variant: This variant (f) lacks one exon and contains an alternate exon, which results in a frameshift and an early stop codon, compared to variant c. The encoded isoform (f) has a shorter and distinct C-terminus, compared to isoform c."
3. NP_001161834.1 protocadherin-11 X-linked isoform g precursor: "Transcript Variant: This variant (g) lacks two consecutive in-frame exons in the central coding region, compared to variant c. The encoded isoform (g) is shorter, compared to isoform c."
4. NP_001161835.1 protocadherin-11 X-linked isoform h precursor: "Transcript Variant: This variant (h) lacks two in-frame exons in the central coding region, compared to variant c. The encoded isoform (h) is shorter, compared to isoform c."
5. NP_116750.1 protocadherin-11 X-linked isoform c precursor: "Transcript Variant: This variant (c) represents the longest transcript and encodes the longest isoform (c)."
6. NP_116751.1 protocadherin-11 X-linked isoform d precursor: "Transcript Variant: This variant (d) lacks an in-frame exon in the central coding region, compared to variant c. The encoded isoform (d) is shorter, compared to isoform c."

Gene ID: 51294 is PCDH12 protocadherin 12: "This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 6 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene localizes to the region on chromosome 5 where the protocadherin gene clusters reside. The exon organization of this transcript is similar to that of the gene cluster transcripts, notably the first large exon, but no significant sequence homology exists. The function of this cellular adhesion protein is undetermined but mouse protocadherin 12 does not bind catenins and appears to have no affect on cell migration or growth."

1. NP_057664.1 protocadherin-12 precursor.

Gene ID: 57575 is PCDH10 protocadherin 10: "This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This family member contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein is a cadherin-related neuronal receptor thought to function in the establishment of specific cell-cell connections in the brain. This gene plays a role in inhibiting cancer cell motility and cell migration. Alternative splicing results in multiple transcript variants encoding different isoforms."

1. NP_065866.1 protocadherin-10 isoform 2 precursor: "Transcript Variant: This variant (2) is intronless, and its 3' terminal end extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 2 which is shorter, and has a distinct C-terminus, compared to isoform 1."
2. NP_116586.1 protocadherin-10 isoform 1 precursor: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."

Gene ID: 64881 is PCDH20 protocadherin 20: "This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This gene encodes a protein which contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. Although its specific function is undetermined, the cadherin-related neuronal receptor is thought to play a role in the establishment and function of specific cell-cell connections in the brain."

1. NP_073754.2 protocadherin-20 precursor.

Gene ID: 83259 is PCDH11Y protocadherin 11 Y-linked: "This gene belongs to the protocadherin family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing seven cadherin repeats, a transmembrane domain, and a cytoplasmic tail that differs from those of the classical cadherins. This gene is located on the Y chromosome in a block of X/Y homology and is very closely related to its paralog on the X chromosome. The protein is thought to play a role in cell-cell recognition during development of the central nervous system. Alternative splicing results in multiple transcript variants encoding different isoforms."

1. NP_001265548.1 protocadherin-11 Y-linked isoform a: "Transcript Variant: This variant (d, also known as Ty2) contains an alternate exon in the 5' UTR, compared to variant a. Variants a and d encode the same isoform (a)."

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."

Gene ID: 1013 is CDH15 cadherin 15 aka CDH3; CDHM; MCAD; MRD3; CDH14: "This gene is a member of the cadherin superfamily of genes, encoding calcium-dependent intercellular adhesion glycoproteins. Cadherins consist of an extracellular domain containing 5 cadherin domains, a transmembrane region, and a conserved cytoplasmic domain. Transcripts from this particular cadherin are expressed in myoblasts and upregulated in myotubule-forming cells. The protein is thought to be essential for the control of morphogenetic processes, specifically myogenesis, and may provide a trigger for terminal muscle cell differentiation."

1. NP_004924.1 cadherin-15 preproprotein.

Gene ID: 1014 is CDH16 cadherin 16: "This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. Mapped to a previously identified cluster of cadherin genes on chromosome 16q22.1, the gene localizes with superfamily members CDH1, CDH3, CDH5, CDH8 and CDH11. The protein consists of an extracellular domain containing 6 cadherin domains, a transmembrane region and a truncated cytoplasmic domain but lacks the prosequence and tripeptide HAV adhesion recognition sequence typical of most classical cadherins. Expression is exclusively in kidney, where the protein functions as the principal mediator of homotypic cellular recognition, playing a role in the morphogenic direction of tissue development. Alternatively spliced transcript variants encoding distinct isoforms have been identified."

1. NP_001191673.1 cadherin-16 isoform 2 precursor: "Transcript Variant: This variant (2) lacks an in-frame segment in the 3' coding region, as compared to variant 1. The resulting isoform (2) lacks an internal segment, as compared to isoform 1."
2. NP_001191674.1 cadherin-16 isoform 3 precursor: "Transcript Variant: This variant (3) lacks an in-frame segment in the 3' coding region, as compared to variant 1. The resulting isoform (3) lacks an internal segment, as compared to isoform 1."
3. NP_001191675.1 cadherin-16 isoform 4 precursor: "Transcript Variant: This variant (4) lacks an in-frame segment in the 5' coding region, as compared to variant 1. The resulting isoform (4) lacks an internal segment, as compared to isoform 1."
4. NP_004053.1 cadherin-16 isoform 1 precursor: "Transcript Variant: This variant (1) encodes the longest isoform (1)."

Gene ID: 1015 is CDH17 cadherin 17 aka HPT1; CDH16; HPT-1: "This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. The encoded protein is cadherin-like, consisting of an extracellular region, containing 7 cadherin domains, and a transmembrane region but lacking the conserved cytoplasmic domain. The protein is a component of the gastrointestinal tract and pancreatic ducts, acting as an intestinal proton-dependent peptide transporter in the first step in oral absorption of many medically important peptide-based drugs. The protein may also play a role in the morphological organization of liver and intestine. Alternative splicing results in multiple transcript variants."

1. NP_001138135.1 cadherin-17 precursor: "Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein."
2. NP_004054.3 cadherin-17 precursor: "Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein."

Gene ID: 1016 is CDH18 cadherin 18 aka CDH14; CDH24; CDH14L: "This gene encodes a type II classical cadherin from the cadherin superfamily of 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. This particular cadherin is expressed specifically in the central nervous system and is putatively involved in synaptic adhesion, axon outgrowth and guidance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene."

1. NP_001161139.1 cadherin-18 isoform 2 precursor: "Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 2, which has a shorter and distinct C-terminus, compared to isoform 1. Variant 2 and 9 encode the same protein (isoform 2). This isoform (2) may undergo proteolytic processing similar to isoform 1."
2. NP_001278885.1 cadherin-18 isoform 1 preproprotein: "Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 3, 5, 6, and 7 encode the same protein (isoform 1)."
3. NP_001278886.1 cadherin-18 isoform 3 precursor: "Transcript Variant: This variant (4) differs in the 5' UTR and has an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 3, which has a shorter and distinct C-terminus, compared to isoform 1. Variant 4 and 8 encode the same protein (isoform 3). This isoform (3) may undergo proteolytic processing similar to isoform 1."
4. NP_001336485.1 cadherin-18 isoform 1 preproprotein: "Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1, 3, 5, 6, and 7 encode the same protein (isoform 1)."
5. NP_001336487.1 cadherin-18 isoform 1 preproprotein: "Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 1. Variants 1, 3, 5, 6, and 7 encode the same protein (isoform 1)."
6. NP_001336488.1 cadherin-18 isoform 1 preproprotein: "Transcript Variant: This variant (7) differs in the 5' UTR compared to variant 1. Variants 1, 3, 5, 6, and 7 encode the same protein (isoform 1)."
7. NP_001336489.1 cadherin-18 isoform 3 precursor: "Transcript Variant: This variant (8) differs in the 5' UTR and uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 3, which has a shorter and distinct C-terminus, compared to isoform 1. Variant 4 and 8 encode the same protein (isoform 3). This isoform (3) may undergo proteolytic processing similar to isoform 1."
8. NP_001336490.1 cadherin-18 isoform 2 precursor: "Transcript Variant: This variant (9) differs in the 5' UTR and uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 2, which has a shorter and distinct C-terminus, compared to isoform 1. Variant 2 and 9 encode the same protein (isoform 2). This isoform (2) may undergo proteolytic processing similar to isoform 1."
9. NP_001336491.1 cadherin-18 isoform 4: "Transcript Variant: This variant (10) differs in the 5' UTR and uses a downstream start codon compared to variant 1. It encodes isoform 4 which has a shorter N-terminus compared to isoform 1. Variants 11 and 12 encode the same protein (isoform 4)."
10. NP_001336492.1 cadherin-18 isoform 4: "Transcript Variant: This variant (11) contains an alternate exon in the 5' region, which results in the use of a downstream start codon compared to variant 1. It encodes isoform 4 which has a shorter N-terminus compared to isoform 1. Variants 11 and 12 encode the same protein (isoform 4)."
11. NP_004925.1 cadherin-18 isoform 1 preproprotein: "Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1, 3, 5, 6, and 7 encode the same protein (isoform 1)."

Gene ID: 1951 is CELSR3 cadherin EGF LAG seven-pass G-type receptor 3 aka FMI1; EGFL1; HFMI1; MEGF2; ADGRC3; CDHF11; RESDA1: "This gene belongs to the flamingo subfamily, which is included in the cadherin superfamily. The flamingo cadherins consist of nonclassic-type cadherins that do not interact with catenins. They are plasma membrane proteins containing seven epidermal growth factor-like repeats, nine cadherin domains and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic feature of their subfamily. The encoded protein may be involved in the regulation of contact-dependent neurite growth and may play a role in tumor formation."

1. NP_001398.2 cadherin EGF LAG seven-pass G-type receptor 3 precursor.

Gene ID: 1952 is CELSR2 cadherin EGF LAG seven-pass G-type receptor 2: "The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consists of nonclassic-type cadherins; a subpopulation that does not interact with catenins. The flamingo cadherins are located at the plasma membrane and have nine cadherin domains, seven epidermal growth factor-like repeats and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic unique to this subfamily. It is postulated that these proteins are receptors involved in contact-mediated communication, with cadherin domains acting as homophilic binding regions and the EGF-like domains involved in cell adhesion and receptor-ligand interactions. The specific function of this particular member has not been determined."

1. NP_001399.1 cadherin EGF LAG seven-pass G-type receptor 2 precursor.

Gene ID: 8642 is DCHS1 dachsous cadherin-related 1 aka FIB1; MVP2; CDH19; CDH25; CDHR6; PCDH16; VMLDS1: "This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing."

1. NP_003728.1 protocadherin-16 precursor.

Gene ID: 9620 is CELSR1 cadherin EGF LAG seven-pass G-type receptor 1: "The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consists of nonclassic-type cadherins; a subpopulation that does not interact with catenins. The flamingo cadherins are located at the plasma membrane and have nine cadherin domains, seven epidermal growth factor-like repeats and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic unique to this subfamily. It is postulated that these proteins are receptors involved in contact-mediated communication, with cadherin domains acting as homophilic binding regions and the EGF-like domains involved in cell adhesion and receptor-ligand interactions. This particular member is a developmentally regulated, neural-specific gene which plays an unspecified role in early embryogenesis."

1. NP_055061.1 cadherin EGF LAG seven-pass G-type receptor 1 precursor.

Gene ID: 28513 is CDH19 cadherin 19 aka CDH7; CDH7L2: "This gene is one of three related type II cadherin genes situated in a cluster on chromosome 18. The encoded protein is a calcium dependent cell-cell adhesion glycoprotein containing five extracellular cadherin repeats. Loss of cadherins may be associated with cancer formation. Alternative splicing results in multiple transcript variants for this gene."

1. NP_001257957.1 cadherin-19 isoform 2 preproprotein: "Transcript Variant: This variant (2) lacks two alternate exons in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1."
2. NP_066976.1 cadherin-19 isoform 1 preproprotein: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1)."
3. NR_073130.2 RNA Sequence: "Transcript Variant: This variant (3) uses an alternate splice site in an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD)."

Gene ID: 28316 is CDH20 cadherin 20 aka Cdh7; CDH7L3: "This gene is a type II classical cadherin from the cadherin superfamily and one of three cadherin 7-like genes located in a cluster on chromosome 18. The encoded membrane protein is a calcium dependent cell-cell adhesion glycoprotein 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 HAV cell adhesion recognition sequence specific to type I cadherins. Since disturbance of intracellular adhesion is a prerequisite for invasion and metastasis of tumor cells, cadherins are considered prime candidates for tumor suppressor genes."

1. NP_114097.2 cadherin-20 preproprotein.

Gene ID: 54798 is DCHS2 dachsous cadherin-related 2 aka CDHJ; CDH27; CDHR7; PCDHJ; PCDH23: "This gene encodes a large protein that contains many cadherin domains and likely functions in cell adhesion. Genome-wide association studies suggest that this gene may be important in Alzheimer's disease, compressive strength index, and appendicular lean mass."

1. NP_001136024.1 protocadherin-23 isoform 2: "Transcript Variant: This variant (2) contains an alternate 3' terminal exon and lacks several 3' coding exons, compared to variant 3. It encodes isoform 2, which is shorter and has a distinct C-terminus, compared to isoform 3."
2. NP_001345164.1 protocadherin-23 isoform 3: "Transcript Variant: This variant (3) represents the longer transcript and encodes the longer isoform 3."

Gene ID: 60437 is CDH26 cadherin 26: "This gene encodes a member of the cadherin protein family. Cadherins are a family of calcium-dependent adhesion molecules that mediate cell-cell adhesion in all solid tissues and modulate a wide variety of processes, including cell polarization, migration and differentiation. Cadherin domains occur as repeats in the extracellular region and are thought to contribute to the sorting of heterogeneous cell types and the maintenance of orderly structures such as epithelium. This protein is expressed in gastrointestinal epithelial cells and may be upregulated during allergic inflammation. This protein interacts with alpha integrins and may also be involved in leukocyte migration and adhesion."

1. NP_001335133.1 cadherin-like protein 26 isoform c: "Transcript Variant: This variant (c) use an alternate exon in the 5' UTR and 5' coding region and lacks a large portion of the 5' coding region, compared to variant a. The encoded isoform (c) has a a shorter and distinct N-terminus compared to isoform a."
2. NP_068582.2 cadherin-like protein 26 isoform b: "Transcript Variant: This variant (b) use an alternate exon in the 5' UTR and 5' coding region and lacks a large portion of the 5' coding region, compared to variant a. The encoded isoform (b) has a a shorter and distinct N-terminus compared to isoform a."
3. NP_817089.1 cadherin-like protein 26 isoform a precursor: "Transcript Variant: This variant (a) represents the longer transcript and encodes the longer isoform (a)."
4. NR_145482.2 RNA Sequence: "Transcript Variant: This variant (d) uses an alternate splice site compared to variant a. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant a, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD)."

Gene ID: 64072 is CDH23 cadherin related 23 aka PITA5; USH1D; CDHR23: "This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described."

1. NP_001165401.1 cadherin-23 isoform 3 precursor: "Transcript Variant: This variant (3) differs in the 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (3) has a distinct C-terminus and is shorter than isoform 1."
2. NP_001165402.1 cadherin-23 isoform 4 precursor: "Transcript Variant: This variant (4) differs in the 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (4) has a distinct C-terminus and is shorter than isoform 1."
3. NP_001165403.1 cadherin-23 isoform 5 precursor: "Transcript Variant: This variant (5) differs in the 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (5) has a distinct C-terminus and is shorter than isoform 1."
4. NP_001165404.1 cadherin-23 isoform 6: "Transcript Variant: This variant (6) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (6, also referred to as isoform B1) is shorter than isoform 1."
5. NP_001165405.1 cadherin-23 isoform 7: "Transcript Variant: This variant (7) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. This variant also lacks an in-frame exon in the 3' coding region compared to variant 1. The encoded isoform (7, also referred to as isoform B2) is shorter than isoform 1."
6. NP_001165406.1 cadherin-23 isoform 8: "Transcript Variant: This variant (8) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (8, also referred to as isoform C1) has a distinct N-terminus and is shorter than isoform 1."
7. NP_001165407.1 cadherin-23 isoform 9: "Transcript Variant: This variant (9) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. This variant also lacks an in-frame exon in the 3' coding region compared to variant 1. The encoded isoform (9, also referred to as isoform C2) has a distinct N-terminus and is shorter than isoform 1."
8. NP_071407.4 cadherin-23 isoform 1 precursor: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1)."
9. NP_443068.1 cadherin-23 isoform 2 precursor: "Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (2) has a distinct C-terminus and is shorter than isoform 1."

Gene ID: 64403 is CDH24 cadherin 24 aka CDH11L.

1. NP_071923.2 cadherin-24 isoform 1 precursor: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."
2. NP_659422.2 cadherin-24 isoform 2 precursor: "Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1."

Gene ID: 64405 is CDH22 cadherin 22 aka C20orf25; dJ998H6.1: "This gene is a member of the cadherin superfamily. The gene product is composed of five cadherin repeat domains and a cytoplasmic tail similar to the highly conserved cytoplasmic region of classical cadherins. Expressed predominantly in the brain, this putative calcium-dependent cell adhesion protein may play an important role in morphogenesis and tissue formation in neural and non-neural cells during development and maintenance of the brain and neuroendocrine organs."

1. NP_067071.1 cadherin-22 precursor.

Gene ID: 222256 is CDHR3 cadherin related family member 3 aka CDH28.

1. NP_001288090.1 cadherin-related family member 3 isoform 2: "Transcript Variant: This variant (2) lacks part of the 5' coding region, and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1."
2. NP_689963.2 cadherin-related family member 3 isoform 1 precursor: "Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1)."

Gene ID: 389118 is CDHR4 cadherin related family member 4 aka CDH29; PRO34300.

1. NP_001007541.2 cadherin-related family member 4 precursor.

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