Envoplakin-like, also known as EVPLL, is a protein which in humans is encoded by the EVPLL gene. The EVPLL gene plays a role in structural molecule activity, intermediate filament (IF) organization, and wound healing. The orthologs of EVPLL are conserved across a variety of vertebrates such as birds, mammals, and bony fishes.

Gene Envoplakin-Like (EVPLL) is a protein-coding gene located on chromosome 17 (17p11.2) in humans. The gene has 1979 base pairs and spans approximately 11.89 kilobases on the direct strand. EVPLL consists of 11 exons that produce two alternatively spliced mRNAs. EVPLL is located in the gene neighborhood of MFAP4 (upstream) and SHMT1 (downstream).

Transcript The EVPLL gene is predominantly expressed in tissues like the skin and esophagus, where it is localized in the cytoplasm, membrane, and cornified envelope.

The human EVPLL has 7 isoforms with varying protein lengths. +Isoforms of Homo sapiens (human) EVPLL GeneIsoform Number (#)mRNA Accession Number from NCBI (#)mRNA Length (bp)Protein Accession Number (#)Protein Length (aa)Molecular Weight (kDA)1XM_047436537.12547XP_047292493.130133.82XM_011523982.31970XP_011522284.129833.63XM_011523983.31154XP_011522285.129232.94XM_011523985.31883XP_011522287.126929.95XM_011523986.3885XP_011522289.122523.26XM_047436538.11936XP_047292494.120722.87XM_011523987.3845XP_011522289.117118.7

Protein The molecular weight of the EVPLL protein without molecular modifications is 34.0kDa and the isoelectric point is 5.80. There is a notably high content of glutamine, making up 11% of the protein.

Function The EVPLL protein expression is associated with structural molecule activity such as intermediate filament (IF) organization and wound healing. It is predicted to enable structural integrity within epithelial tissues, particularly in the cytoplasm and membrane.

Domains, motifs, and secondary structure There are 2 spectrin-repeat domains from amino acids 1-93 and 190-286. There are 2 coiled-coil regions which includes amino acids 1-63 and 66-95.

Protein interactions EVPLL has interactions with Capicua transcriptional repressor (CIC), a transcriptional regulator located in the nucleus. EVPLL also has interactions with Parkin RBR E3 ubiquitin protein ligase (PARK2), a ubiquitin tagging protein located in the cytoplasm. EVPLL has interactions with Schalfen-like protein (SLFNL1) and Carbonic anhydrase-related protein 11 (CA11). EVPLL has been experimentally determined to have interactions with neuroblastoma breakpoint family member 4 (NBPF4).

Gene-level regulation EVPLL is expressed in a variety of tissues, but most notably high in the esophagus, skin, and testis. There is a relatively high amount of expression in the lungs, stomach, and kidney. RNA sequencing of 20 human transcriptomes show that the RNA is expressed highly in the lungs, prostate, kidney, and thymus of adults. The RNA is expressed highly in the lungs at 20 weeks and stomach at 18-20 weeks gestational age. The EVPLL protein abundance in all human tissues are at a level below 1ppm, indicating a lower-than-average expression level compared to other human proteins.

Protein-Level Regulation With subcellular localization, EVPLL is likely to reside within the nucleus and cytoplasm. EVPLL lacks transmembrane segments and signal peptides.

Homology and evolution

Orthologs EVPLL has homologs across various vertebrate species, including mammals, birds, and fishes. The EVPLL lacks orthologs within invertebrates. EVPLLGenus and SpeciesCommon NameTaxonomic GroupMedian Date of Divergence (MYA)Accession #Sequence Length (aa)Sequence Identity to Human Protein (%)Sequence Similarity to Human Protein (%)MammaliaHomo sapiensHumanPrimates0NP_001138599.1301100100Pan troglodytesChimpanzeePrimates6.4XP_054526963.13079192.9Gorilla gorilla gorillaWestern lowland gorillaPrimates8.6XP_063562703.13029597Pongo pygmaeusBornean orangutanPrimates15.2XP_054314372.12939293.7Hylobates molochSilvery gibbonPrimates19.5XP_058284091.129257.964Leptonychotes weddelliiWeddell sealCarnivora94XP_006752112.229379.785.7Equus przewalskiiPrzewalskis horsePerissodactyla94XP_008540515.12936270.6Physeter macrocephalusSperm whaleCetacea94XP_054939461.128257.867.6AvesMalurus melanocephalusRed-backed fairywrenPasseriformes319XP_057234942.129250.264.2Cygnus olorMute swanAnseriformes319XP_040386607.129249.262Neopsephotus bourkiiBourke's parrotPsittaciformes319XP_061210355.129248.960.7Merops nubicusCarmine bee-eaterCoraciiformes319XP_008948521.122540.150.5ReptilesSphaerodactylus townsendiTownsend's least geckoSquamata319XP_048345833.129248.162.5Varanus komodoensisKomodo DragonSquamata319XP_044309908.129246.959.9Ophiophagus hannahKing CobraSquamata319ETE73234.125938.754Anolis carolinensisGreen AnoleSquamata319XP_008115008.12952843.1AmphibiansAmbystoma mexicanumAxolotlUrodela352XP_069510819.129245.761.3Xenopus laevisAfrican clawed frogAnura352XP_041433928.128942.857.2Bombina bombinaFire-bellied toadAnura352XP_053565186.129140.756.5Rhinatrema bivittatumTwo-lined caecilianGymnophiona352XP_029432184.128928.445.6FishesChanodichthys erythropterusPredatory carpCypriniformes429XP_067228760.12943754.3Paralichthys olivaceusJapanese flounderPleuronectiformes429XP_069381809.129534.850.6Cyprinus carpioCommon carpCypriniformes429XP_042571485.129034.149.8Danio rerioZebrafishCypriniformes429XP_003201660.328725.539.5

Clinical significance

Head and neck squamous cell carcinoma EVPLL is one of the genes highlighted to be over-expressed in patients with better survival outcomes in Head and Neck Squamous Cell Carcinoma (HNSCC).

Alzheimer's disease Current research suggests that EVPLL may contribute to neurodegeneration through its proximity to AD-associated piRNA DQ586113.

References