] Parvulin, a 92-

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 ...

protein discovered in E. coli in 1994,Rahfeld JU, Schierhorn A, Mann KH. (1994). A novel peptidyl-prolyl cis/trans isomerase from Escherichia coli. ''FEBS Lett'' 343:65. is the smallest known protein with

prolyl isomerase Prolyl isomerase (also known as peptidylprolyl isomerase or PPIase) is an enzyme () found in both prokaryotes and eukaryotes that interconverts the ''cis'' and ''trans'' isomers of peptide bonds with the amino acid proline. Proline has an ...

activity, which catalyzes the ''cis''-''trans'' isomerization of

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 ...

peptide bonds. Although parvulin has no

homology Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor * Sequence homology, biological homology between DNA, RNA, or protein sequences *Homologous chrom ...

with larger prolyl isomerases such as

cyclophilin Cyclophilins (CYPs) are a family of proteins named after their ability to bind to ciclosporin (cyclosporin A), an immunosuppressant which is usually used to suppress rejection after internal organ transplants. They are found in all domains of l ...

and

FKBP FKBP, or FK506 binding protein, is a family of proteins that have prolyl isomerase activity and are related to the cyclophilins in function, though not in amino acid sequence. FKBPs have been identified in many eukaryotes, ranging from yeast to h ...

, it does share structural features with subdomains of other proteins involved in preparing

secrete 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...

d proteins for export from the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

.Balbach J, Schmid FX. (2000). Proline isomerizarion and its catalysis in protein folding. ''In Mechanisms of Protein Folding'' 2nd ed. Ed. RH Pain. ''Frontiers in Molecular Biology'' series. Oxford University Press: Oxford, UK. Although parvulin is as active as the larger prolyl isomerases against a short proline-containing test

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

, it has lower relative activity against biological substrates, possibly because the larger molecules have a higher ability to bind the substrate peptide.Scholz C, Rahfeld J, Fischer G, Schmid FX. (1997). Catalysis of protein folding by parvulin. ''J Mol Biol'' 273(3):752-62. Parvulin itself contains proline residues and its

folding Fold, folding or foldable may refer to: Arts, entertainment, and media * ''Fold'' (album), the debut release by Australian rock band Epicure * Fold (poker), in the game of poker, to discard one's hand and forfeit interest in the current pot *Abov ...

can be accelerated by the presence of cyclophilin; parvulin folding can also be

autocatalytic A single chemical reaction is said to be autocatalytic if one of the reaction products is also a catalyst for the same or a coupled reaction.Steinfeld J.I., Francisco J.S. and Hase W.L. ''Chemical Kinetics and Dynamics'' (2nd ed., Prentice-Hall 199 ...

. A

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

homolog of parvulin known as Pin1 is required to execute the transition from

G2 phase G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the o ...

M phase The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

in the

cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...

.Gothel SF, Marahiel MA. (1999). Peptidyl-prolyl cis-trans isomerases, a superfamily of ubiquitous folding catalysts. ''Cell Mol Life Sci'' 55(3):423-36. Absence of Pin1 activity in humans has also been implicated in the folding and processing of the

amyloid precursor protein Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many biological tissue, tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator ...

, whose degradation product is the cytotoxic peptide amyloid beta implicated in

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

.Pastorino L, Sun A, Lu PJ, Zhou XZ, Balastik M, Finn G, Wulf G, Lim J, Li SH, Li X, Xia W, Nicholson LK, Lu KP. (2006). The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. ''Nature'' 440(7083):528-34. In addition to Pin1, higher eukaryotes contain an additional parvulin gene, whose core sequence is highly conserved in all multi-cellular organisms examined so far, but absent from yeast. In humans the locus of this parvulin resides on chromosome Xq13 and encodes two protein species,

Par14 Par14 (eukaryotic homolog of parvulin, EHPF) is a member of the parvulin family of peptidyl-prolyl-cis/trans-isomerases (PPIases) in humans, which possesses prolyl isomerase activity. History In 1999, Par14 was identified by two groups independe ...

and

Par17 Par17, a member of the parvulin family of peptidyl-prolyl-cis/trans-isomerases (PPIases), is an isoform of parvulin 14 (Par14) and originates from alternative transcription initiation of the PIN4 gene on chromosome Xq13 in humans. Par17, which c ...

.Mueller JW, Bayer P. (2008).Small Family with Key Contacts: Par14 and Par17 Parvulin Proteins, Relatives of Pin1, Now Emerge in Biomedical Research. '' Perspectives in Medicinal Chemistry 2'', 11–20

/ref> Par17,Mueller JW, Kessler D, Neumann D, Stratmann T, Papatheodorou P, Hartmann-Fatu C, Bayer P. (2006). Characterization of novel elongated Parvulin isoforms that are ubiquitously expressed in human tissues and originate from alternative transcription initiation. '' BMC Molecular Biology'', 7:9

/ref>Kessler D, Papatheodorou P, Stratmann T, Dian EA, Hartmann-Fatu C, Rassow J, Bayer P, Mueller JW. (2007) . The DNA Binding Parvulin Par17 is Targeted to the Mitochondrial Matrix by a Recently Evolved Prepeptide Uniquely Present in Hominidae. '' BMC Biology'', 5:3

/ref> which is exclusively expressed in hominids and humans, is an N-terminal extended version of Par14 and results from alternative transcription initiation.

References

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