Glutamate Rich Protein 2 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, respo ...

in humans encoded by the gene ''ERICH2''. This protein is expressed heavily in male tissues specifically in the

testes A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoster ...

, and proteins are specifically found in the nucleoli fibrillar center and the

vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...

of these testicular cells. The protein has multiple protein interactions which indicate that it may play a role in histone modification and proper histone functioning.

Gene

ERICH2 is located on human

Chromosome 2 Chromosome 2 is one of the twenty-three pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 2 is the second-largest human chromosome, spanning more than 242 million base pairs and representing almost e ...

, at 2q31.1. It contains 10 distinct

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 sequen ...

s. The gene itself is 28,930 base pairs long and is flanked by the EIF2S2P4 and GAD1 genes. There are no known

paralog 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 spec ...

s of the ERICH2 gene.

mRNA

ERICH2 transcription produces three validated distinct mRNA variants. The longest transcript variant is 1,388

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

s in length, 1,311 of which are coding. The second variant differs from the first in its 5' UTR. It also has coding sequence differences and a distinct N-terminus compared to variant 1. Variant 3 lacks several exons, has a distinct 3' UTR and C- terminus coding region. This variant is also shorter than the other two at 1,063 base pairs. Cartoon 3

Protein

The ERICH2 protein is 436

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 am ...

s in length, and has a

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

of approximately 48,000 kD, with an isoelectric point of approximately 5. The protein is determined to be rich in the amino acid

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

and low in

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

and

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

Motifs and domains

Two known motifs were found in the human ERICH2 protein. The KKNT motif functions in cAMP- and cGMP- dependent protein

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, wh ...

, this protein motif was found only in primates. There is also a FGRR motif conserved in mammals that is defined as an

amidation In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is p ...

site. Finally the ERICH2 protein contains the PHA03247 domain that is 32 amino acids long. This domain is not generally conserved through orthologs and the function is unknown. It is present in the proteins that make up the

herpes Herpes simplex is a viral infection caused by the herpes simplex virus. Infections are categorized based on the part of the body infected. Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold s ...

virion.

Structure and localization

Secondary structure prediction shows one

alpha helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues e ...

and one

beta strand The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a gen ...

formation. The alpha helix encompasses the entire conserved section as seen in the cartoon of the ERICH2 protein. The beta strand is predicted 12 amino acids down from the amidation site and encompasses 4 amino acids. Four

nuclear localization signals A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysines o ...

were found in the protein, two pat4 signals and two pat7 signals, their locations are shown in the cartoon. It is predicted in the 78th percent that the protein resides in the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

Expression

ERICH2 is not ubiquitously expressed. It however, has been shown to be expressed narrowly in the

choroid plexus The choroid plexus, or plica choroidea, is a plexus of cells that arises from the tela choroidea in each of the ventricles of the brain. Regions of the choroid plexus produce and secrete most of the cerebrospinal fluid (CSF) of the central nerv ...

of a developing fetus and in the

of adults.

Lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...

and female tissue expression were also present but expression was greatly decreased. Proteins are specifically located in the nucleoli fibrillar center and the vesicles within cells.

Regulation of expression

Many phosphorylation sites are predicted for the ERICH2 protein. None are predicted on tyrosines only on serines and the threonines. There is also a predicted acetylation site at the N-terminus of the protein, specifically it is predicted on the third amino acid. Many SOX/ SRY-sex/testis determining and related HMG box factor transcription factors and

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

related transcription factors are predicted to bind and regulate transcription of ERICH2.

Function

Interacting proteins

ERICH2 interacts with proteins in the H2A family. The H2A proteins specifically play a role in the octamer structure of

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wr ...

. ERICH2 is specifically known to interact with the

H2AFY Core histone macro-H2A.1 is a protein that in humans is encoded by the ''H2AFY'' gene. Function Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist ...

protein, which plays a key role in the stable

X chromosome inactivation X-inactivation (also called Lyonization, after English geneticist Mary Lyon) is a process by which one of the copies of the X chromosome is inactivated in therian female mammals. The inactive X chromosome is silenced by being packaged into a ...

and can function by replacing a normal H2A in certain

nucleosome A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamen ...

s and thus repressing transcription. ERICH2 is also known to interact with the protein SDCB1 which functions in vesicle trafficking and the regulation of growth and proliferation of certain cancer cells. The IWS1 protein also interacts with ERICH2. This protein functions as a transcription factor and plays a key role in defining the composition of the RNA polymerase II elongation complex. This complex then plays a role in

modification and proper splicing. Two-hybrid assays and other protein interaction methods have shown an interaction with the PSORS1C2 protein, but the function of this protein remains unknown.

Homology

No paralogs for the ERICH2 protein are known. ERICH2 has 124 known

ortholog 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 spec ...

s spanning multiple taxa.

References

{{Reflist Proteins