Envoplakin-Like


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 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 is a protein-coding gene located on chromosome 17 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 and SHMT1.

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.
Isoform Number mRNA Accession Number from NCBI mRNA Length Protein Accession Number Protein Length Molecular Weight
1XM_047436537.12547XP_047292493.130133.8
2XM_011523982.31970XP_011522284.129833.6
3XM_011523983.31154XP_011522285.129232.9
4XM_011523985.31883XP_011522287.126929.9
5XM_011523986.3885XP_011522289.122523.2
6XM_047436538.11936XP_047292494.120722.8
7XM_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 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, a transcriptional regulator located in the nucleus. EVPLL also has interactions with Parkin RBR E3 ubiquitin protein ligase, a ubiquitin tagging protein located in the cytoplasm. EVPLL has interactions with Schalfen-like protein and Carbonic anhydrase-related protein 11. EVPLL has been experimentally determined to have interactions with neuroblastoma breakpoint family member 4.

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">Sequence homology">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 Accession #Sequence Length Sequence Identity to Human Protein Sequence Similarity to Human Protein
MammaliaHomo sapiensHumanPrimates0NP_001138599.1301100100
Pan troglodytesChimpanzeePrimates6.4XP_054526963.13079192.9
Gorilla gorilla gorillaWestern lowland gorillaPrimates8.6XP_063562703.13029597
Pongo pygmaeusBornean orangutanPrimates15.2XP_054314372.12939293.7
Hylobates molochSilvery gibbonPrimates19.5XP_058284091.129257.964
Leptonychotes weddelliiWeddell sealCarnivora94XP_006752112.229379.785.7
Equus przewalskiiPrzewalskis horsePerissodactyla94XP_008540515.12936270.6
Physeter macrocephalusSperm whaleCetacea94XP_054939461.128257.867.6
AvesMalurus melanocephalusRed-backed fairywrenPasseriformes319XP_057234942.129250.264.2
Cygnus olorMute swanAnseriformes319XP_040386607.129249.262
Neopsephotus bourkiiBourke's parrotPsittaciformes319XP_061210355.129248.960.7
Merops nubicusCarmine bee-eaterCoraciiformes319XP_008948521.122540.150.5
ReptilesSphaerodactylus townsendiTownsend's least geckoSquamata319XP_048345833.129248.162.5
Varanus komodoensisKomodo DragonSquamata319XP_044309908.129246.959.9
Ophiophagus hannahKing CobraSquamata319ETE73234.125938.754
Anolis carolinensisGreen AnoleSquamata319XP_008115008.12952843.1
AmphibiansAmbystoma mexicanumAxolotlUrodela352XP_069510819.129245.761.3
Xenopus laevisAfrican clawed frogAnura352XP_041433928.128942.857.2
Bombina bombinaFire-bellied toadAnura352XP_053565186.129140.756.5
Rhinatrema bivittatumTwo-lined caecilianGymnophiona352XP_029432184.128928.445.6
FishesChanodichthys erythropterusPredatory carpCypriniformes429XP_067228760.12943754.3
Paralichthys olivaceusJapanese flounderPleuronectiformes429XP_069381809.129534.850.6
Cyprinus carpioCommon carpCypriniformes429XP_042571485.129034.149.8
Danio 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.

Alzheimer's disease

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