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Conserved domains on  [gi|1423310308|ref|NP_001351756|]
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periphilin-1 isoform 14 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
periphilin-like cd22896
Vertebrate periphilin-1 and similar proteins; This family contains periphilin (PPHLN1), a ...
 266-322 2.86e-35

Vertebrate periphilin-1 and similar proteins; This family contains periphilin (PPHLN1), a component of the Human Silencing Hub (HUSH) complex containing three proteins: periphilin, TASOR and MPP8 (also called MPHOSPH8) and mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3 (histone H3 lysine 9 trimethylation), as well as MORC2, a DNA-binding ATPase. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed. In human, periphilin-1, the protein encoded by the gene PPHLN1, is involved in epithelial differentiation and contributes to epidermal integrity and barrier formation. It is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Oncogenic fusion protein of Fibroblast Growth Factor Receptor 2 (FGRF2) joined to periphilin 1, that occurs through a chromosomal translocation, is associated with intrahepatic cholangiocarcinoma; FGFR2-PPHLN1 activity requiring FGRF2-driven tyrosine kinase domain and PPHLN1 dimerization domain strongly drives cellular proliferation.


:

Pssm-ID: 439377  Cd Length: 74  Bit Score: 125.80  E-value: 2.86e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1423310308 266 SQLTTRSKAIASKTKEIEQVYRQDCETFGMVVKMLIEKDPSLEKSIQFALRQNLHEI 322
Cdd:cd22896     1 SLLDTRSKAIRAKKKEIEEAYRQDCETFGMVVKMLISKDPSLEKPIQFALRENLREI 57
HERV-K_REC super family cl24310
Rec (regulator of expression encoded by corf) of HERV-K-113; REC is a family of rec proteins ...
 421-456 2.12e-03

Rec (regulator of expression encoded by corf) of HERV-K-113; REC is a family of rec proteins from the HERV-K viral polyprotein family. Rec is a functional homolog of Rev and Rex, and binds to an RNA element, the Rec-responsive element (RcRE), in the 3'LTR of HTDV/HERV-K transcripts. Thus Rec mediates nuclear export of RNA by binding to its responsive element, RcRE, present in a transcript. The human small glutamine-rich tetratricopeptide repeat-containing protein (hSGT) that controls mitotic processes and is a checkpoint protein during pro-metaphase is found to be a Rec-interacting partner.interferes with its role as a negative regulator of the androgen receptor, leading to enhanced androgen receptor activity. HERV-K(HML-2) elements benefit from this enhanced activity, as this leads to a vicious cycle that can result in increased cell proliferation, an inhibition of apoptosis, and eventually tumourigenesis.


The actual alignment was detected with superfamily member pfam15695:

Pssm-ID: 292323  Cd Length: 87  Bit Score: 37.15  E-value: 2.12e-03
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1423310308 421 TWGMLKKTTQEAERILLRTQTPFTPENLFLAMLSVV 456
Cdd:pfam15695  31 TWAQLKKLTQLATKYLENTKVTQTPESMLLAALMIV 66
 
Name Accession Description Interval E-value
periphilin-like cd22896
Vertebrate periphilin-1 and similar proteins; This family contains periphilin (PPHLN1), a ...
 266-322 2.86e-35

Vertebrate periphilin-1 and similar proteins; This family contains periphilin (PPHLN1), a component of the Human Silencing Hub (HUSH) complex containing three proteins: periphilin, TASOR and MPP8 (also called MPHOSPH8) and mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3 (histone H3 lysine 9 trimethylation), as well as MORC2, a DNA-binding ATPase. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed. In human, periphilin-1, the protein encoded by the gene PPHLN1, is involved in epithelial differentiation and contributes to epidermal integrity and barrier formation. It is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Oncogenic fusion protein of Fibroblast Growth Factor Receptor 2 (FGRF2) joined to periphilin 1, that occurs through a chromosomal translocation, is associated with intrahepatic cholangiocarcinoma; FGFR2-PPHLN1 activity requiring FGRF2-driven tyrosine kinase domain and PPHLN1 dimerization domain strongly drives cellular proliferation.


Pssm-ID: 439377  Cd Length: 74  Bit Score: 125.80  E-value: 2.86e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1423310308 266 SQLTTRSKAIASKTKEIEQVYRQDCETFGMVVKMLIEKDPSLEKSIQFALRQNLHEI 322
Cdd:cd22896     1 SLLDTRSKAIRAKKKEIEEAYRQDCETFGMVVKMLISKDPSLEKPIQFALRENLREI 57
Lge1 pfam11488
Transcriptional regulatory protein LGE1; This family of proteins is conserved from fungi to ...
 265-321 3.55e-18

Transcriptional regulatory protein LGE1; This family of proteins is conserved from fungi to human. In yeasts it is involved in the ubiquitination of histones H2A and H2B. This ubiquitination step is a vital one in the regulation of the transcriptional activity of RNA polymerase II. In S. cerevisiae, Rad6 and Bre1 are present in a complex, also containing Lge1, that is required for H2B ubiquitination. Bre1 is the H2B ubiquitin ligase that interacts with acidic activators, such as Gal4, and recruits Rad6 and its binding partner Lge1 to target promoters. In S. pombe the equivalent protein to Lge1 appears to be Shf1. In human, periphilin acts a transcriptional co-repressor and regulates cell cycle progression.


Pssm-ID: 431907  Cd Length: 64  Bit Score: 78.45  E-value: 3.55e-18
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1423310308 265 DSQLTTRSKAIASKTKEIEQVYRQDCETFGMVVKMLIEKDPSLEKSIQFALRQNLHE 321
Cdd:pfam11488   1 DLDDESTLKKIESKYKELEQLDKKLCELQLKVLKLELELDLLEEQAERDALNVQLTQ 57
HERV-K_REC pfam15695
Rec (regulator of expression encoded by corf) of HERV-K-113; REC is a family of rec proteins ...
 421-456 2.12e-03

Rec (regulator of expression encoded by corf) of HERV-K-113; REC is a family of rec proteins from the HERV-K viral polyprotein family. Rec is a functional homolog of Rev and Rex, and binds to an RNA element, the Rec-responsive element (RcRE), in the 3'LTR of HTDV/HERV-K transcripts. Thus Rec mediates nuclear export of RNA by binding to its responsive element, RcRE, present in a transcript. The human small glutamine-rich tetratricopeptide repeat-containing protein (hSGT) that controls mitotic processes and is a checkpoint protein during pro-metaphase is found to be a Rec-interacting partner.interferes with its role as a negative regulator of the androgen receptor, leading to enhanced androgen receptor activity. HERV-K(HML-2) elements benefit from this enhanced activity, as this leads to a vicious cycle that can result in increased cell proliferation, an inhibition of apoptosis, and eventually tumourigenesis.


Pssm-ID: 292323  Cd Length: 87  Bit Score: 37.15  E-value: 2.12e-03
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1423310308 421 TWGMLKKTTQEAERILLRTQTPFTPENLFLAMLSVV 456
Cdd:pfam15695  31 TWAQLKKLTQLATKYLENTKVTQTPESMLLAALMIV 66
 
Name Accession Description Interval E-value
periphilin-like cd22896
Vertebrate periphilin-1 and similar proteins; This family contains periphilin (PPHLN1), a ...
 266-322 2.86e-35

Vertebrate periphilin-1 and similar proteins; This family contains periphilin (PPHLN1), a component of the Human Silencing Hub (HUSH) complex containing three proteins: periphilin, TASOR and MPP8 (also called MPHOSPH8) and mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3 (histone H3 lysine 9 trimethylation), as well as MORC2, a DNA-binding ATPase. The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed. In human, periphilin-1, the protein encoded by the gene PPHLN1, is involved in epithelial differentiation and contributes to epidermal integrity and barrier formation. It is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Oncogenic fusion protein of Fibroblast Growth Factor Receptor 2 (FGRF2) joined to periphilin 1, that occurs through a chromosomal translocation, is associated with intrahepatic cholangiocarcinoma; FGFR2-PPHLN1 activity requiring FGRF2-driven tyrosine kinase domain and PPHLN1 dimerization domain strongly drives cellular proliferation.


Pssm-ID: 439377  Cd Length: 74  Bit Score: 125.80  E-value: 2.86e-35
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1423310308 266 SQLTTRSKAIASKTKEIEQVYRQDCETFGMVVKMLIEKDPSLEKSIQFALRQNLHEI 322
Cdd:cd22896     1 SLLDTRSKAIRAKKKEIEEAYRQDCETFGMVVKMLISKDPSLEKPIQFALRENLREI 57
Lge1 pfam11488
Transcriptional regulatory protein LGE1; This family of proteins is conserved from fungi to ...
 265-321 3.55e-18

Transcriptional regulatory protein LGE1; This family of proteins is conserved from fungi to human. In yeasts it is involved in the ubiquitination of histones H2A and H2B. This ubiquitination step is a vital one in the regulation of the transcriptional activity of RNA polymerase II. In S. cerevisiae, Rad6 and Bre1 are present in a complex, also containing Lge1, that is required for H2B ubiquitination. Bre1 is the H2B ubiquitin ligase that interacts with acidic activators, such as Gal4, and recruits Rad6 and its binding partner Lge1 to target promoters. In S. pombe the equivalent protein to Lge1 appears to be Shf1. In human, periphilin acts a transcriptional co-repressor and regulates cell cycle progression.


Pssm-ID: 431907  Cd Length: 64  Bit Score: 78.45  E-value: 3.55e-18
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1423310308 265 DSQLTTRSKAIASKTKEIEQVYRQDCETFGMVVKMLIEKDPSLEKSIQFALRQNLHE 321
Cdd:pfam11488   1 DLDDESTLKKIESKYKELEQLDKKLCELQLKVLKLELELDLLEEQAERDALNVQLTQ 57
HERV-K_REC pfam15695
Rec (regulator of expression encoded by corf) of HERV-K-113; REC is a family of rec proteins ...
 421-456 2.12e-03

Rec (regulator of expression encoded by corf) of HERV-K-113; REC is a family of rec proteins from the HERV-K viral polyprotein family. Rec is a functional homolog of Rev and Rex, and binds to an RNA element, the Rec-responsive element (RcRE), in the 3'LTR of HTDV/HERV-K transcripts. Thus Rec mediates nuclear export of RNA by binding to its responsive element, RcRE, present in a transcript. The human small glutamine-rich tetratricopeptide repeat-containing protein (hSGT) that controls mitotic processes and is a checkpoint protein during pro-metaphase is found to be a Rec-interacting partner.interferes with its role as a negative regulator of the androgen receptor, leading to enhanced androgen receptor activity. HERV-K(HML-2) elements benefit from this enhanced activity, as this leads to a vicious cycle that can result in increased cell proliferation, an inhibition of apoptosis, and eventually tumourigenesis.


Pssm-ID: 292323  Cd Length: 87  Bit Score: 37.15  E-value: 2.12e-03
                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1423310308 421 TWGMLKKTTQEAERILLRTQTPFTPENLFLAMLSVV 456
Cdd:pfam15695  31 TWAQLKKLTQLATKYLENTKVTQTPESMLLAALMIV 66
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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