# 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 (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 Gene :
| Isoform Number (#) | mRNA Accession Number from NCBI (#) | mRNA Length (bp) | Protein Accession Number (#) | Protein Length (aa) | Molecular Weight (kDA) |
| 1 | XM_047436537.1 | 2547 | XP_047292493.1 | 301 | 33.8 |
| 2 | XM_011523982.3 | 1970 | XP_011522284.1 | 298 | 33.6 |
| 3 | XM_011523983.3 | 1154 | XP_011522285.1 | 292 | 32.9 |
| 4 | XM_011523985.3 | 1883 | XP_011522287.1 | 269 | 29.9 |
| 5 | XM_011523986.3 | 885 | XP_011522289.1 | 225 | 23.2 |
| 6 | XM_047436538.1 | 1936 | XP_047292494.1 | 207 | 22.8 |
| 7 | XM_011523987.3 | 845 | XP_011522289.1 | 171 | 18.7 |

## 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.
| EVPLL | Genus and Species | Common Name | Taxonomic Group | Median Date of Divergence (MYA) | Accession # | Sequence Length (aa) | Sequence Identity to Human Protein (%) | Sequence Similarity to Human Protein (%) |
| Mammalia | Homo sapiens | Human | Primates | 0 | NP_001138599.1 | 301 | 100 | 100 |
| | Pan troglodytes | Chimpanzee | Primates | 6.4 | XP_054526963.1 | 307 | 91 | 92.9 |
| | Gorilla gorilla gorilla | Western lowland gorilla | Primates | 8.6 | XP_063562703.1 | 302 | 95 | 97 |
| | Pongo pygmaeus | Bornean orangutan | Primates | 15.2 | XP_054314372.1 | 293 | 92 | 93.7 |
| | Hylobates moloch | Silvery gibbon | Primates | 19.5 | XP_058284091.1 | 292 | 57.9 | 64 |
| | Leptonychotes weddellii | Weddell seal | Carnivora | 94 | XP_006752112.2 | 293 | 79.7 | 85.7 |
| | Equus przewalskii | Przewalskis horse | Perissodactyla | 94 | XP_008540515.1 | 293 | 62 | 70.6 |
| | Physeter macrocephalus | Sperm whale | Cetacea | 94 | XP_054939461.1 | 282 | 57.8 | 67.6 |
| Aves | Malurus melanocephalus | Red-backed fairywren | Passeriformes | 319 | XP_057234942.1 | 292 | 50.2 | 64.2 |
| | Cygnus olor | Mute swan | Anseriformes | 319 | XP_040386607.1 | 292 | 49.2 | 62 |
| | Neopsephotus bourkii | Bourke's parrot | Psittaciformes | 319 | XP_061210355.1 | 292 | 48.9 | 60.7 |
| | Merops nubicus | Carmine bee-eater | Coraciiformes | 319 | XP_008948521.1 | 225 | 40.1 | 50.5 |
| Reptiles | Sphaerodactylus townsendi | Townsend's least gecko | Squamata | 319 | XP_048345833.1 | 292 | 48.1 | 62.5 |
| | Varanus komodoensis | Komodo Dragon | Squamata | 319 | XP_044309908.1 | 292 | 46.9 | 59.9 |
| | Ophiophagus hannah | King Cobra | Squamata | 319 | ETE73234.1 | 259 | 38.7 | 54 |
| | Anolis carolinensis | Green Anole | Squamata | 319 | XP_008115008.1 | 295 | 28 | 43.1 |
| Amphibians | Ambystoma mexicanum | Axolotl | Urodela | 352 | XP_069510819.1 | 292 | 45.7 | 61.3 |
| | Xenopus laevis | African clawed frog | Anura | 352 | XP_041433928.1 | 289 | 42.8 | 57.2 |
| | Bombina bombina | Fire-bellied toad | Anura | 352 | XP_053565186.1 | 291 | 40.7 | 56.5 |
| | Rhinatrema bivittatum | Two-lined caecilian | Gymnophiona | 352 | XP_029432184.1 | 289 | 28.4 | 45.6 |
| Fishes | Chanodichthys erythropterus | Predatory carp | Cypriniformes | 429 | XP_067228760.1 | 294 | 37 | 54.3 |
| | Paralichthys olivaceus | Japanese flounder | Pleuronectiformes | 429 | XP_069381809.1 | 295 | 34.8 | 50.6 |
| | Cyprinus carpio | Common carp | Cypriniformes | 429 | XP_042571485.1 | 290 | 34.1 | 49.8 |
| | Danio rerio | Zebrafish | Cypriniformes | 429 | XP_003201660.3 | 287 | 25.5 | 39.5 |

## 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.