Leucine zipper protein 2 is a protein that in humans is encoded by the LUZP2 gene. There are no orthologs in invertebrates, but many in vertebrates. It is a transcription factor found in eukaryotes.
Gene The LUZP2 gene is found on the short arm of chromosome 11 at position 11p14.3. It is located on the plus strand.
The gene contains 23 introns, and can produce 11 alternatively spliced mRNAs.
Protein structure LUZP2 encodes a leucine zipper protein that is 346 amino acids in length, and has a molecular weight of ~39 kDa. This protein is secreted, and is found mostly expressed within the brain and spinal cord.
The protein contains a signal peptide, 3 glycosylation sites, a leucine zipper region, and a disordered region. It also contains 3 highly conserved "QLKE" amino acid repeats.
Leucine zipper
The leucine zipper motif is located on positions 164-192 of the protein, and contains 4 conserved lysine and 4 conserved leucine residues. Leucine zippers usually facilitate protein-protein interactions and contain many amphipathic helices that form a left-handed dimeric coiled-coil structure. They also often contain leucine residues spaced 7 amino acids apart.
Abundance
Protein Abundance LUZP2 protein is present in higher amounts than most proteins, but is more abundant in the cerebral cortex and brain. Immunohistochemical staining using anti-LUZP2 rabbit antibodies shows it to be present in low levels in the pancreas and high in the cerebral cortex. Interestingly, it is present in high levels in neuronal projections, suggesting it could have some role in the development of the vertebral nervous system.
In situ hybridization Based on in situ hybridization studies, LUZP2 mRNA is expressed at low levels throughout the brain, but more highly concentrated in the regions of the forebrain, the thalamus, and the hypothalamus. LUZP2 is also least expressed in the cerebellum compared to other structures.
Clinical findings
Based on a data mining study investigating low-grade Gliomas, LUZP2 downregulation was found to be associated with higher-grade tumors, suggesting that LUZP2 expression decreased as tumors became more aggressive. Low LUZP2 expression was also associated with worse overall survival in patients with low-grade gliomas across multiple cohorts.
This gene has also been found deleted in some patients with Wilms tumor-aniridia-ganomalies-mental retardation (WAGR) syndrome.
Evolution LUZP2 has many orthologs in vertebrates. It is highly conserved in mammals, birds, and reptiles.
LUZP2 is expected to have first appeared in cartilaginous fish around 462 million years ago, and is evolving at an intermediate rate, slower than fibrinogen alpha, but faster than cytochrome c.
LUZP2Genus and SpeciesCommon NameTaxonomic OrderMedian Date of Divergence (MYA)Accession #Sequence Length (aa)Sequence Identity to Human Protein (%)Sequence Similarity to Human Protein (%)MammalsHomo sapiensHumanPrimates0NP_001009909.2346100.0100.0Mesocricetus auratusGolden hamsterRodentia87XP_040589238.134583.289.6Ursus arctosBrown bearCarnivora94XP_048073596.234780.289.1Dromiciops gliroidesColocolo opossumMarsupialia160XP_043829349.134570.979.8Ornithorhynchus anatinusPlatypusMonotremata180XP_028914921.134770.480.2BirdsCygnus olorMute swanAnseriformes319XP_040415405.134367.176.6Gallus gallusRed junglefowlGalliformes319NP_001186450.134466.274.9Falco cherrugSaker falconFalconiformes319XP_027654513.131466.274.3Corvus brachyrhynchosAmerican crowPasseriformes319XP_017581874.135265.873.7ReptilesDermochelys coriaceaLeatherback sea turtleTestudines319XP_038262088.134366.675.2Notechis scutatusMainland tiger snakeSquamta319XP_026520543.133663.272.2Varanus komodoensisKomodo dragonSquamata319XP_044282044.136459.871.0Alligator mississippiensisAmerican alligatorCrocodilia319XP_019332548.242555.962.9AmphibiansRhinatrema bivittatumTwo-lined caecilianGymnophiona352XP_029438260.134262.274.9Xenopus laevisAfrican clawed frogAnura352XP_018113009.134460.672.1Pleurodeles waltlIberian ribbed newtUrodela352XP_069078053.134859.771.4FishesProtopterus annectensWest african lungfishCeratodontiformes408XP_043939274.134954.767.6Periophthalmus magnuspinnatusMudskipperGobiiformes429XP_033847668.134746.659.6Danio rerioZebrafishCypriniformes429NP_001108187.134649.360.3Amblyraja radiataThorny skateRajiformes462XP_032894536.130643.057.9Carcharodon carchariasGreat white sharkLamniformes462XP_041052683.130748.261.0
Possible Interactions LUZP2 mostly interacts with proteins found the nucleus. Proteins that showed the most promising interactions with LUZP2 include the serine/threonine kinase TNIK, GAS2, and CBX5. +ProteinFunctionLocationMethodSourcec-Src Tyrosine Kinase (CSK)Regulation of embryonic development and cell growthMany, including nucleusSynthetic lethalityBioGRIDHeterogenous Ribonucleoprotein L (HBRNPL)Nucelocytoplasmic exportNucleus, extracellularAffinity capture-RNABioGRIDChromobox 5 (CBX5)Formation of kinetochores and heterochromatinNucleusTandem affinity purificationIntActEstrogen-receptor 1 (ESR1)Nuclear hormone receptorMany, including nucleusAffinity chromography technologyIntActTRAF2 and NCK Interacting Kinase (TNIK)Ser/thr kinase that activates Wnt signaling pathwayMany, including nucleusTwo hybrid fragment pooling approachingIntActGrowth Arrest Specific 2 (GAS2)Microfilament dynamics during cell cycle and apoptosisCytosol, cytoskeletonCo-expression, Co-mentioned in Pubmed abstractsSTRINGFamily With Sequence Similarity 81 Member A (FAM81A)Enables protein bindingCytosol, nucleusCo-expression, Co-mentioned in Pubmed abstractsSTRINGCyclic AMP-Responsive Element-Binding Protein 3 (CREB3)Leucine-zipper protein, binds cAMP-response elements and regulates proliferationGolgi, cytosol, endoplasmic reticulum, nucleusCo-mentioned in Pubmed abstractsSTRINGAnkyrin Repeat Domain 55 (ANKRD55)Enables protein bindingNucleusCo-mentioned in Pubmed abstractsSTRINGClathrin Heavy Chain Linker Domain Containing 1 (CLHC1)Enables protein bindingCytosol, nucleusCo-mentioned in Pubmed abstractsSTRINGZinc Finger DHHC-Type Palmitoyltransferase 19 (ZDHHC19)Mediates palmitoylation proteins such as RRAS and SQSTM1, positively regualtes autophagyGolgi, endoplasmic reticulum, nucleus, plasma membraneCo-mentioned in PubMed abstractSTRING
References