6SWG,6SWG


Conserved Protein Domain Family
periphilin-like

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cd22896: periphilin-like 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 439377
Aligned: 33 rows
Threshold Bit Score: 90.7452
Created: 16-Feb-2021
Updated: 17-Oct-2022
Structure
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Program:
Drawing:
Aligned Rows:
 
heterotrimer
Conserved site includes 23 residues -Click on image for an interactive view with Cn3D
Feature 1:heterotrimer interface [polypeptide binding site]
Evidence:
  • Structure:6SWG: Homo sapiens periphilin-1 binds TASOR; contacts at 4.0A

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1             #   ##  #  ##  ##  ##  #                 #  ##  ##  ## ##  ##  #     
6SWG_B        19 SQLTTRSKAIASKTKEIEQVYRQDCETFGMVVKMLIEKDPSLEKSIQFALRQNLHEIGERCVEELKHFIAEYDT 92  human
XP_022081390 398 EVIQTKLERLQAKKEEIIRAYKQDCDTFATVVRMLIRKDPELEQRLQQALRENLTEIGQRCVQELQEMVEQIKD 471 crown-of-thorns starfish
XP_013412561 557 GLTVENMKMLMAKKKEVEKAYRQDCETFATVVKMLISKDQSLEEPIQRSLKLNLQEIGQHCIEEVQHYIEVLQS 630 Lingula anatina
ELT95611     350 GLAPDKLMLVKDKKEEIERAYRQDCETFAAVTKMLVSKDPTLEDQLQRCLRDNLKEIGQRCILELKDSIEQIKS 423 Capitella teleta
PAA84610     282 DAGDGILRLVRAKKAELERAYRQDCDTFAVVAKVLVSKNSSLEGPVRDALREALRDIGQHCVEELREFARTLAI 355 Macrostomum lignano
PAA80829     369 SLSESSLGKLRAKKAELEESYRQDCDTFTIVVKMLISKDPQLESRIRSALKETLREIGQQCVEELRDYVRHLES 442 Macrostomum lignano
XP_002599643 474 SKEDLMLKQIRKKRREIEEAYRQDCETIGTVCKMLITKDPSIEEKLSPALKECLKDLGDRCIQELKDAIKTLED 547 Florida lancelet
XP_007897706 470 ALREARTAAILARKDKLEEAFHWDCKVFATVAKMLVRMQPGVERQMQSALRKTLRFVSNRCVQRLQRFIAEYDH 543 elephant shark
XP_004948491 471 TSTDPRSAAILSKKESIEQGYHEFCLNFAMVSMMLLQKEPSMEGVLMKALRANLRELRHRLLKEMEDFIQQYDV 544 chicken
XP_018104804 365 TALALRTAFILTKKEELEMAYAQDCRTFAFVADTLLKKNPSIEAAVASALRSSLYDLAGRCVHELTSYIDSYDR 438 African clawed frog

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