Leucine-Rich Single-Pass Membrane Protein 1 (LSMEM1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that, in humans, is encoded by the LSMEM1

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Gene

In humans, LSMEM1 is located on chromosome 7q31.1. LSMEM1 neighbors the gene

IFRD1 Interferon-related developmental regulator 1 is a protein that in humans is encoded by the ''IFRD1'' gene. The gene is expressed mostly in neutrophils, skeletal and cardiac muscle, the brain, and the pancreas. The rat and the mouse homolog genes o ...

in humans. Aliases for LSMEM1 include C7orf53, chromosome 7

open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a Prokaryote, prokaryotic DNA sequence, where only one of the #Six-fra ...

53, and FLJ39575. The human

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

is 1686 base pairs long and the gene contains 5

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequenc ...

s. The human mRNA also has a

5' UTR The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly upstream from the initiation codon. This region is important for the regulation o ...

and a

3' UTR In molecular genetics, the three prime untranslated region (3′-UTR) is the section of messenger RNA (mRNA) that immediately follows the translation termination codon. The 3′-UTR often contains regulatory regions that post-transcriptionall ...

. The 5' UTR goes from mRNA position 1 to 341, and the 3' UTR goes from mRNA position 738 to 1686.

Protein

The protein LSMEM1 encodes in humans is 131

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

s long and has a molecular weight ranging from 14.2 to 14.5 kDal. Its

isoelectric point The isoelectric point (pI, pH(I), IEP), is the pH at which a molecule carries no net electrical charge or is electrically neutral in the statistical mean. The standard nomenclature to represent the isoelectric point is pH(I). However, pI is also ...

in humans is about 5, making it slightly acidic. LSMEM1 is an

integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All ''transmembrane proteins'' are IMPs, but not all IMPs are transmembrane proteins. IMPs comprise a sign ...

and a

transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...

Besides its transmembrane segment, it is mainly made up of coils and relatively few

beta strands Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiod ...

. As its name implies, LSMEM1 only has one transmembrane segment. The predicted

post-translational modifications Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribosome ...

to the human LSMEM1 protein are

glycation Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proces ...

and

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, ...

. There is no predicted

signal peptide A signal peptide (sometimes referred to as signal sequence, targeting signal, localization signal, localization sequence, transit peptide, leader sequence or leader peptide) is a short peptide (usually 16-30 amino acids long) present at the N-ter ...

for the human protein.

Homology/Evolution

There are no known

paralogs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a sp ...

in humans for LSMEM1. Orthologous proteins exist mainly in mammals,

bird Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweig ...

s, and reptiles. There are also more distant orthologs in amphibians and

sarcopterygii Sarcopterygii (; ) — sometimes considered synonymous with Crossopterygii () — is a taxon (traditionally a class or subclass) of the bony fishes known as the lobe-finned fishes. The group Tetrapoda, a mostly terrestrial superclass includ ...

. LSMEM1 does not show up in

invertebrate Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...

fungi A fungus (plural, : fungi or funguses) is any member of the group of Eukaryote, eukaryotic organisms that includes microorganisms such as yeasts and Mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified ...

, or

prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...

s. LSMEM1 also contains a conserved

domain of unknown function A domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. As of 201 ...

DUF4577. When the human protein encoded by LSMEM1 is compared to a known quickly evolving protein (

fibrinopeptide The fibrinopeptides, fibrinopeptide A (FpA) and fibrinopeptide B (FpB), are peptides which are located in the central region of the fibrous glycoprotein fibrinogen (factor I) and are cleaved by the enzyme thrombin (factor IIa) to convert fibrin ...

s) and a known slowly evolving protein (

cytochrome c The cytochrome complex, or cyt ''c'', is a small hemeprotein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins and plays a major role in cell apoptosis. Cytochrome c is hig ...

), LSMEM1 appears to be slowly evolving.

Expression

In humans, LSMEM1 is very highly expressed in skeletal muscle. In humans, LSMEM1 also shows high expression in nerve tissue, moderate expression in the uterus, testis, bone marrow, heart, and intestines, and low expression in the brain and pancreas. It also shows expression in both the fetal and adult stages of life in humans. LSMEM1 is predicted to have a 615 base pair promoter in humans just upstream of its transcriptional start site.

Interacting Proteins

Some

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

s that are predicted to bind to the promoter of LSMEM1 in humans are:

SRF SRF may refer to: Organisations: * Sudan Revolutionary Front, alliance of armed groups formed in 2011 * Syria Revolutionaries Front, formed in December 2013 * Schweizer Radio und Fernsehen, German-language broadcaster in Switzerland * SRF Limite ...

EVI1 MDS1 and EVI1 complex locus protein EVI1 (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the ''MECOM'' gene. EVI ...

, SOX,

ETS ETS or ets may refer to: Climate change, environment and economy * Emissions trading scheme ** European Union Emission Trading Scheme Organisations * European Thermoelectric Society * Evangelical Theological Society Education * École de techno ...

, LTSM, and TALE transcription factors. Many of the transcription factors thought to bind to the LSMEM1 promoter in humans have activity in biological processes like cell differentiation, cell cycle, cell growth, and development. There are 3 main proteins thought to interact with the human protein encoded by the gene LSMEM1 that were determined via

two-hybrid screening Two-hybrid screening (originally known as yeast two-hybrid system or Y2H) is a molecular biology technique used to discover protein–protein interactions (PPIs) and protein–DNA interactions by testing for physical interactions (such as bind ...

(LSMEM2 and MAL) and reconstituted complex (APP) experiments. A reconstituted complex experiment detects interactions between purified proteins

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology and ...

. The 3 proteins thought to interact with LSMEM1 are: MAL,

APP App, Apps or APP may refer to: Computing * Application software * Mobile app, software designed to run on smartphones and other mobile devices * Web application or web app, software designed to run inside a web browser * Adjusted Peak Performan ...

, and LSMEM2. All three of these interacting proteins are integral membrane proteins, just as LSMEM1 is.

Clinical Significance

LSMEM1 expression levels in humans are greatly decreased in septic skeletal muscle. For humans, the LSMEM1 protein has 17 SNP

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Substitution of protein from DNA mutations Missense m ...

s within its coding sequence. The LSMEM1 protein has been shown to be prevalent in the serum of patients with

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

and that it binds to diagnostic biomarkers of Parkinson's Disease as a protein

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

References

{{reflist Genes Human proteins