{{Short description|Protein-coding gene in the species Homo sapiens}} Proline-rich protein 16 ('''PRR16''') is a protein coding gene in ''Homo sapiens.''<ref name=":02">{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/51334|title=PRR16 proline rich 16 [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|access-date=2019-06-17}}</ref> 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.<ref>{{Cite web|url=http://useast.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000184838;r=5:120464300-120687332|title=Gene: PRR16 (ENSG00000184838) - Summary - Homo sapiens - Ensembl genome browser 97|website=useast.ensembl.org|access-date=2019-07-30}}</ref>
==== Gene Neighborhood ==== Cytogenic band: 5q23.1
alt=
<ref>{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=PRR16&keywords=prr16|title=PRR16 Gene|last=|first=|date=|website=www.genecards.org|archive-url=|archive-date=|access-date=2019-07-30}}</ref>
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.<ref name=":02" />
== mRNA == === Splice Variants === PRR16 has five known splice variants, each with a different processed transcript. alt=|700x700px<ref>{{Cite web|url=http://dec2014.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000184838;r=5:120464278-120687332|title=Ensembl genome browser 78: Homo sapiens - Summary - Gene: PRR16 (ENSG00000184838)|website=dec2014.archive.ensembl.org|access-date=2019-07-30}}</ref>
=== 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.<ref name=":02" />
== 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.<ref>{{Cite web|url=https://www.ebi.ac.uk/Tools/services/web/toolresult.ebi?jobId=saps-I20190730-173830-0373-51758108-p2m|title=SAPS Results|website=www.ebi.ac.uk|access-date=2019-07-30}}</ref><ref>{{Cite web|url=http://isoelectric.org/calculate.php|title=CALCULATION OF PROTEIN ISOELECTRIC POINT|website=isoelectric.org|access-date=2019-07-30}}</ref> The protein does not interact with the membrane.
==== Secondary Structure ==== thumb|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.<ref>{{Cite web|url=http://dis.embl.de/cgiDict.py|title=DisEMBL 1.5 - Predictors of intrinsic protein disorder|website=dis.embl.de|access-date=2019-08-01}}</ref>
==== Tertiary Structure ==== This structure was predicted by analyzing the amino acid sequence using I-TASSER. The final result can be seen below.<ref>{{Cite web|url=https://zhanglab.ccmb.med.umich.edu/I-TASSER/output/S482172/|title=I-TASSER results|website=zhanglab.ccmb.med.umich.edu|access-date=2019-08-01|archive-date=2019-08-01|archive-url=https://web.archive.org/web/20190801024739/https://zhanglab.ccmb.med.umich.edu/I-TASSER/output/S482172/|url-status=dead}}</ref> {| class="wikitable" |+alt=|none|frame|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.<ref>{{Cite web|url=http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5D4739AF0000062FFDE7AACA&wait=20|title=NetGlycate 1.0 Server - prediction results|website=www.cbs.dtu.dk|access-date=2019-08-04}}</ref> * Predicted nuclear export signals (NES) at Leu 39 and Leu 41.<ref>{{Cite web|url=http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5D473B330000137B8DED7CEE&wait=20|title=NetNES 1.1 Server - prediction results|website=www.cbs.dtu.dk|access-date=2019-08-04}}</ref> * 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.<ref>{{Cite web|url=http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5D473C000000137BA05A8D5A&wait=20|title=NetOGlyc 4.0 Server - prediction results|website=www.cbs.dtu.dk|access-date=2019-08-04}}</ref> * 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.<ref>{{Cite web|url=http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=5D473FB8000004DDF9E77DB6&wait=20|title=NetPhos 3.1 Server - prediction results|website=www.cbs.dtu.dk|access-date=2019-08-04}}</ref> * Predicted sumoylation at site Lys 133.<ref>{{Cite web|url=http://sumosp.biocuckoo.org/showResult.php|title=GPS-SUMO: Prediction of SUMOylation Sites & SUMO-interaction Motifs|website=sumosp.biocuckoo.org|access-date=2019-08-04|archive-date=2018-05-06|archive-url=https://web.archive.org/web/20180506035609/http://sumosp.biocuckoo.org/showResult.php|url-status=dead}}</ref>
== 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.<ref>{{Cite web|url=https://psort.hgc.jp/form2.html|title=PSORT II Prediction|website=psort.hgc.jp|access-date=2019-08-01}}</ref>
== 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.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3113:202795|title=GDS3113 / 202795|website=www.ncbi.nlm.nih.gov|access-date=2019-08-01}}</ref>
== Interacting Proteins == {| class="wikitable" !Protein !Function<ref>{{Cite web|url=https://string-db.org/|title=STRING: functional protein association networks|website=string-db.org|access-date=2019-08-04}}</ref> !Tool |- |Abelson-interactor 2 (ABI2) |Regulation of cell growth and actin filament reorganization |Biogrid,<ref>{{Cite web|url=https://thebiogrid.org/119481/summary/homo-sapiens/prr16.html|title=PRR16 Result Summary {{!}} BioGRID|website=thebiogrid.org|access-date=2019-08-04}}</ref> IntAct,<ref>{{Cite web|url=https://www.ebi.ac.uk/intact/interactions?conversationContext=1|title=PRR16 Interactions|last=|first=|date=|website=|archive-url=|archive-date=|access-date=}}</ref> Mentha<ref>{{Cite web|url=http://mentha.uniroma2.it/result.php#|title=Results - mentha: the interactome browser|website=mentha.uniroma2.it|access-date=2019-08-04}}</ref> |- |Amyloid precursor protein (APP) |Caspase activation and degeneration of both neuronal cell bodies |Biogrid, InnateDB,<ref>{{Cite web|url=https://www.innatedb.com/interactionSearch.do?listType=interaction&participantField=idphysical_molecule&participantKeyword=38581&participantKeywordExact=true|title=InnateDB: Systems Biology of the Innate Immune Response|last=al|first=David Lynn et|website=www.innatedb.com|access-date=2019-08-04}}</ref> Mentha |- |Death-associated protein kinase 1 (DAPK1) |Positive mediator of programmed cell death |Biogrid, IntAct |- |Neural precursor cell expressed developmentally downregulated protein 4-like (NEDD4L) |E3 ubiquitin-protein ligase |Biogrid, InnateDB, Mentha |- |Neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) |E3 ubiquitin-protein ligase |Biogrid, InnateDB |- |Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) |Involved in gastrointestinal immunity |Biogrid |- |Protein phosphatase 1 catalytic subunit alpha (PPP1CA) |Cell division, regulation of glycogen metabolism, muscle contractility, and protein synthesis |Biogrid, InnateDB, IntAct, Mentha |- |Protein phosphatase 1 catalytic subunit gamma (PPP1CC) |Cell division, regulation of glycogen metabolism, muscle contractility, and protein synthesis |Biogrid, InnateDB, Mentha |- |SMAD ubiquitin regulatory factor 1 (SMURF1) |E3 ubiquitin-protein ligase |Biogrid, Mentha |}
== Homology == === Paralogs === alt=|thumb|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.<ref>{{Cite web|url=https://www.genome.jp/tools-bin/clustalw|title=Multiple Sequence Alignment - CLUSTALW|website=www.genome.jp|access-date=2019-07-03}}</ref> 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.<ref>{{Cite web|url=http://timetree.org/|title=TimeTree :: The Timescale of Life|website=timetree.org|access-date=2019-07-01}}</ref> The gene has not been found in any plants, fungi or single celled organisms. The table below compares the known orthologs.<ref>{{Cite web|url=https://blast.ncbi.nlm.nih.gov/Blast.cgi|title=BLAST: Basic Local Alignment Search Tool|website=blast.ncbi.nlm.nih.gov|access-date=2019-08-01}}</ref> {| class="wikitable" !Organism !Common name !Class !Accession number !Sequence Identity !Sequence Similarity |- |''Homo sapiens'' |Human |Mammalia |NP_001287712.1 |100% |100% |- |''Pan paniscus'' |Bonobo |Mammalia |XP_003826752.1 |99% |100% |- |''Mus musculus'' |House mouse |Mammalia |NP_001074693.1 |93% |95% |- |''Ochotona princeps'' |American pika |Mammalia |XP_004586413.1 |91% |94% |- |''Vombatus ursinus'' |Common wombat |Mammalia |XP_027730777.1 |87% |81% |- |''Podarcis muralis'' |Common wall lizard |Reptilia |XP_028604016.1 |88% |91% |- |''Alligator sinensis'' |Chinese alligator |Reptilia |XP_006033732.1 |86% |89% |- |''Chrysemys picta bellii'' |Painted turtle |Reptilia |XP_005305197.1 |88% |91% |- |''Pogona vitticeps'' |Central bearded dragon |Reptilia |XP_020659290.1 |84% |86% |- |''Pseudonaja textilis'' |Eastern brown snake |Reptilia |XP_026576168.1 |81% |84% |- |''Gallus gallus'' |Chicken |Aves |XP_001232593.3 |81% |85% |- |''Columba livia'' |Rock pigeon |Aves |XP_005506281.1 |85% |89% |- |''Haliaeetus leucocephalus'' |Bald eagle |Aves |XP_010560635.1 |82% |86% |- |''Empidonax traillii'' |Willow flycatcher |Aves |XP_027735123.1 |82% |86% |- |''Nanorana parkeri'' |High Himalaya frog |Amphibia |XP_018426570.1 |71% |79% |- |''Xenopus tropicalis'' |Western clawed frog |Amphibia |XP_017946181.1 |72% |79% |- |''Lepisosteus oculatus'' |Spotted gar fish |Actinopterygii |XP_006626913.1 |65% |77% |- |''Callorhinchus milii'' |Australian ghostshark |Chondrichthyes |XP_007897515.1 |64% |75% |- |''Branchiostoma belcheri'' |Lancelet |Amphioxiformes |XP_019614579.1 |47% |78% |- |''Branchiostoma floridae'' |Lancelet |Amphioxiformes |XP_002601582.1 |47% |78% |}
== References == <references />
''Attribution'': Contains public domain text from https://www.ncbi.nlm.nih.gov/gene/51334
Category:Human proteins Category:Genes on human chromosome 5