Proline-rich protein 16 (PRR16) is a protein coding gene in Homo sapiens.[1] The protein is known by the alias Largen.

Gene

Locus

PRR16 is located on the long arm of chromosome 5. It is found at position 5q23.1. It has five known transcripts.[2]

Gene Neighborhood

Cytogenic band: 5q23.1

[3]

The image above shows chromosome five and the various gene locations on it. PRR16 can be seen at the thin red band that has been placed at q23.

Size

PRR16 spans 330,365 bases and encodes for a mRNA that is 1,707 nucleotides. The resulting protein is 304 amino acids long.[1]

mRNA

Splice Variants

PRR16 has five known splice variants, each with a different processed transcript. [4]

Isoforms

There are three known isoforms of PRR16. Isoform 2 contains an additional exon in the 5' region, and it thus differs in the 5' UTR and initiates translation at an alternate start codon, compared to variant 1. Isoform 3 has two variants. The first contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. The second contains alternate 5' exon structure, and it thus differs in the 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. All three isoforms are shorter at the N-terminus, compared to isoform 1.[1]

Protein

Structure

Primary Structure

The PRR16 protein is 304 amino acids in length. It has a molecular weight of 32.8 kDa and an isoelectric point of 8.09.[5][6] The protein does not interact with the membrane.

Secondary Structure

α-helix from amino acid 38 to 52 of PRR16 determined by PHYRE2

The only predictable feature of the PRR16 protein is an α-helix near the N-terminus, spanning about thirty amino acids. The remainder of the protein has a disordered structure.[7]

Tertiary Structure

This structure was predicted by analyzing the amino acid sequence using I-TASSER. The final result can be seen below.[8]

I-TASSER software was used to predict the tertiary structure of PRR16. The blue coils indicate the presence of α-helices, while the remainder is relatively disordered.

Post-Translational Modifications

  • Predicted glycation at Lys 4, Lys 6, Lys 49, Lys 94, Lys 96, Lys 105, Lys 119, Lys 148, Lys 181, and Lys 290.[9]
  • Predicted nuclear export signals (NES) at Leu 39 and Leu 41.[10]
  • Predicted O-linked glycosylation sites at Ser 2, Ser 5, Ser 10, Ser 11, Ser 12, Ser 75, Thr 79, Ser 82, Ser 83, Ser 84, Ser 85, Ser 87, Thr 88, Ser 91, Ser 111, Thr 130, Thr 143, Thr 149, Glu 235, Leu 254, Ser 270, Ser 272, Ser 274, Thr 282, Thr 287, Thr 294, Ser 299, and Thr 300.[11]
  • Predicted phosphorylation at Ser 2, Ser 5, Ser 10, Ser 11, Ser 22, Ser 74, Ser 75, Ser 82, Ser 83, Ser 84, Ser 85, Ser 87, Ser 91, Thr 115, Thr 130, Thr 152, Tyr 224, Thr 254, Thr 282, Ser 299, Thr 300, and Thr 303.[12]
  • Predicted sumoylation at site Lys 133.[13]

Subcellular Location

The k-NN tool suggests the location of PRR16 in the nucleus of the cell with 52.2% certainty. The cytoplasm was predicted with 30.4% certainty, The following locations were predicted with 4.3% certainty: cytoskeleton, plasma membrane, mitochondria, and peroxisome.[14]

Expression

The PRR16 gene is expressed at very low levels throughout the body. It is expressed in the skeletal muscle, heart, lung, skin, portions of the brain, and bone marrow.[15]

Interacting Proteins

ProteinFunction[16]Tool
Abelson-interactor 2 (ABI2)Regulation of cell growth and actin filament reorganizationBiogrid,[17] IntAct,[18] Mentha[19]
Amyloid precursor protein (APP)Caspase activation and degeneration of both neuronal cell bodiesBiogrid, InnateDB,[20] Mentha
Death-associated protein kinase 1 (DAPK1)Positive mediator of programmed cell deathBiogrid, IntAct
Neural precursor cell expressed developmentally downregulated protein 4-like (NEDD4L)E3 ubiquitin-protein ligaseBiogrid, InnateDB, Mentha
Neural precursor cell expressed developmentally downregulated protein 4 (NEDD4)E3 ubiquitin-protein ligaseBiogrid, InnateDB
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2)Involved in gastrointestinal immunityBiogrid
Protein phosphatase 1 catalytic subunit alpha (PPP1CA)Cell division, regulation of glycogen metabolism, muscle contractility, and protein synthesisBiogrid, InnateDB, IntAct, Mentha
Protein phosphatase 1 catalytic subunit gamma (PPP1CC)Cell division, regulation of glycogen metabolism, muscle contractility, and protein synthesisBiogrid, InnateDB, Mentha
SMAD ubiquitin regulatory factor 1 (SMURF1)E3 ubiquitin-protein ligaseBiogrid, Mentha

Homology

Paralogs

Unrooted phylogenetic tree of vertebrate and invertebrate PRR16 orthologs. All abbreviations are the first two letters of genus name and first letter of species name. Tree made with a Neighbor-Joining method using a ClustalW-formatted set of sequences as input.[21]

There are two isoforms of Inhibitory synaptic factor 1 that are known paralogs of PRR16.

Orthologs

PRR16 is found in all classes of vertebrates, including mammals, birds, fish, reptiles and amphibians. The most distant ortholog of PRR16 is in Branchiostoma belcheri and Branchiostoma floridae, which diverged an estimated 684 million years ago.[22] The gene has not been found in any plants, fungi or single celled organisms. The table below compares the known orthologs.[23]

OrganismCommon NameClassAccession NumberSequence IdentitySequence Similarity
Homo sapiensHumanMammaliaNP_001287712.1100%100%
Pan paniscusBonoboMammaliaXP_003826752.199%100%
Mus musculusHouse mouseMammaliaNP_001074693.193%95%
Ochotona princepsAmerican pikaMammaliaXP_004586413.191%94%
Vombatus ursinusCommon wombatMammaliaXP_027730777.187%81%
Podarcis muralisCommon wall lizardReptiliaXP_028604016.188%91%
Alligator sinensisChinese alligatorReptiliaXP_006033732.186%89%
Chrysemys picta belliiPainted turtleReptiliaXP_005305197.188%91%
Pogona vitticepsCentral bearded dragonReptiliaXP_020659290.184%86%
Pseudonaja textilisEastern brown snakeReptiliaXP_026576168.181%84%
Gallus gallusChickenAvesXP_001232593.381%85%
Columba liviaRock pigeonAvesXP_005506281.185%89%
Haliaeetus leucocephalusBald eagleAvesXP_010560635.182%86%
Empidonax trailliiWillow flycatcherAvesXP_027735123.182%86%
Nanorana parkeriHigh Himalaya frogAmphibiaXP_018426570.171%79%
Xenopus tropicalisWestern clawed frogAmphibiaXP_017946181.172%79%
Lepisosteus oculatusSpotted gar fishActinopterygiiXP_006626913.165%77%
Callorhinchus miliiAustralian ghostsharkChondrichthyesXP_007897515.164%75%
Branchiostoma belcheriLanceletAmphioxiformesXP_019614579.147%78%
Branchiostoma floridaeLanceletAmphioxiformesXP_002601582.147%78%

References

Attribution: Contains public domain text from https://www.ncbi.nlm.nih.gov/gene/51334