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SUMO-conjugating enzyme UBC9 is an
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''UBE2I''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe its function.


Expression

Four alternatively spliced transcript variants encoding the same
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
have been found for this gene.


Function

The UBC9
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
encoded by the UBE2I gene constitutes a core machinery in the cell's sumoylation pathway. Sumoylation is a process in which a Small Ubiquitin-like MOdifier (SUMO) is covalently attached to other proteins in order to modify their behaviour. For example, sumoylation may affect a protein's localization in the cell, its ability to interact with other proteins or
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
. UBC9 performs the third step in the sumoylation life cycle: the conjugation step. When SUMO protein precursors are first expressed, they first undergo a maturation step in which the four C-terminal amino acids are removed, revealing a di-
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. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...
motif. In a second step, an E1 activating complex binds to SUMO at its di-glycine and passes it on to the E2 protein Ubc9, where it forms a
thioester In organic chemistry, thioesters are organosulfur compounds with the molecular structure . They are analogous to carboxylate esters () with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix ...
bond with a
cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
residue within Ubc9's catalytic pocket. The loaded Ubc9 is now ready to perform the sumoylation of its various target proteins (also called
substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...
s). It recognizes a particular motif of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
residues in these substrates: A large
hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...
residue, followed by a
lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...
, followed by a spacer, followed by an acidic residue. This motif is usually described in shorthand as ΨKxD/E. The central lysine within the substrate's recognition motif is inserted into the catalytic pocket. There the carboxyl terminus of SUMO's di-glycine forms a
peptide bond In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...
with the ε-amino group of the lysine. This process can be assisted by an E3 ligase protein. The sumoylation process is reversible. SENP proteases can remove SUMO from sumoylated proteins, freeing it to be used in further sumoylation reactions.


Clinical significance relevance

The protein UBC9 encoded by the UBE2I gene has been shown to be targeted by multiple viruses, including HIV and HPV. It has been hypothesized that these viruses hijack UBC9 to serve their own purposes.


Interactions

UBE2I has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with: *
ATF2 Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ''ATF2'' gene. Function This gene encodes a transcription factor that is a member of the leucine zipper family of DNA-binding proteins. This ...
, *
Androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...
, * BLMH, * DACH1, *
DNMT3A DNA (cytosine-5)-methyltransferase 3A (DNMT3A) is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the ''DNMT3A'' gene. This enzyme is ...
, *
DNMT3B DNA (cytosine-5)-methyltransferase 3 beta, is an enzyme that in humans in encoded by the DNMT3B gene. Mutation in this gene are associated with immunodeficiency, centromere instability and facial anomalies syndrome. Function CpG methylation ...
, * DAXX, *
ETS1 Protein C-ets-1 is a protein that in humans is encoded by the ''ETS1'' gene. The protein encoded by this gene belongs to the ETS family of transcription factors. Function There are 28 ETS genes in humans and 27 in mice. They bind the DNA via ...
, *
FHIT Bis(5'-adenosyl)-triphosphatase also known as fragile histidine triad protein (FHIT) is an enzyme that in humans is encoded by the ''FHIT'' gene. Function FHIT is also known as human accelerated region 10. It may, therefore, have played a ke ...
, *
IPO13 Importin-13 is a protein encoded by the IPO13 gene in humans. Importin-13 is a member of the importin-β family of nuclear transport receptors (NTRs) and was first identified as a transport receptor in 2000. According to PSI-blast based secondary ...
, *
MAP3K1 Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal ''MAP3K1'' gene. Function MAP3K1 (or MEKK1) is a serine/threonine kinase and ubiquitin ligase that performs a ...
and *
MITF Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene. MITF is a basic helix-loop-helix leucine zipper transcription factor ...
, *
P53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...
, * PIAS1, * PIAS2, *
RAD51 DNA repair protein RAD51 homolog 1 is a protein encoded by the gene ''RAD51''. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to t ...
, *
RANBP2 RAN binding protein 2 (RANBP2) is protein which in humans is encoded by the ''RANBP2'' gene. It is also known as nucleoporin 358 (Nup358) since it is a member nucleoporin family that makes up the nuclear pore complex. RanBP2 has a mass of 358 kDa ...
, *
RANGAP1 Ran GTPase-activating protein 1 is an enzyme that in humans is encoded by the ''RANGAP1'' gene. Function RanGAP1, is a homodimeric 65-kD polypeptide that specifically induces the GTPase activity of RAN, but not of RAS by over 1,000-fold. R ...
, * SAE2, *
SALL1 Sal-like 1 (Drosophila), also known as SALL1, is a protein which in humans is encoded by the ''SALL1'' gene. As the full name suggests, it is one of the human versions of the ''spalt'' (''sal'') gene known in ''Drosophila''. Function The prot ...
, *
SUMO1 Small ubiquitin-related modifier 1 is a protein that in humans is encoded by the ''SUMO1'' gene. Function This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It is a ubiquitin-like protein a ...
, *
TCF3 Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the ''TCF3'' gene. TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) e ...
, *
TNFRSF1A Tumor necrosis factor receptor 1 (TNFR1), also known as tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) and CD120a, is a ubiquitous membrane receptor that binds tumor necrosis factor-alpha (TNFα). Function The protein encoded ...
, *
TOP1 DNA topoisomerase 1 is an enzyme that in humans is encoded by the ''TOP1'' gene. It is a DNA topoisomerase, an enzyme that catalyzes the transient breaking and rejoining of a single strand of DNA. Function This gene encodes a DNA topoisomeras ...
, and *
WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-rich ...
.


Notes


References

* * * * * * * * * * * * * * * * * * * {{Ubiquitin-conjugating enzymes