Subtilases are a

family Family (from la, familia) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its ...

subtilisin Subtilisin is a protease (a protein-digesting enzyme) initially obtained from ''Bacillus subtilis''. Subtilisins belong to subtilases, a group of serine proteases that – like all serine proteases – initiate the nucleophilic attack on the p ...

-like

serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. ...

s. They appear to have independently and convergently evolved an

Asp Asp may refer to: Places * Asp, part of Densbüren, Aargau, Switzerland * Aspe (''Asp'' in Valencian), Alicante, Spain * Asp Lake, a lake in Minnesota Animals * Asp (fish) * Asp (snake), in antiquity, one of several venomous snakes ** ''Cera ...

Ser Ser or SER may refer to: Places * Ser, a village in Bogdand Commune, Satu Mare County, Romania * Serpens (Ser), an astronomical constellation of the northern hemisphere * Serres, known as Ser in Serbian, a city in Macedonia, Greece Organization ...

His His or HIS may refer to: Computing * Hightech Information System, a Hong Kong graphics card company * Honeywell Information Systems * Hybrid intelligent system * Microsoft Host Integration Server Education * Hangzhou International School, in ...

catalytic triad A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, lip ...

, like in the trypsin serine proteases. The structure of proteins in this family shows that they have an alpha/beta fold containing a 7-stranded parallel

beta sheet 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 g ...

. The subtilisin family is the second largest serine protease family characterised to date. Over 200 subtilases are presently known, more than 170 of which with their complete amino acid sequence. Subtilase is widespread, being found in eubacteria, archaebacteria, eukaryotes and viruses. The vast majority of the family are

endopeptidase Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids (i.e. within the molecule), in contrast to exopeptidases, which break peptide bonds from end-pieces of terminal amino acids. For this re ...

s, although there is an

exopeptidase An exopeptidase is any peptidase that catalyzes the cleavage of the terminal (or the penultimate) peptide bond; the process releases a single amino acid, dipeptide or a tripeptide from the peptide chain. Depending on whether the amino acid is rel ...

, tripeptidyl peptidase. Structures have been determined for several members of the subtilisin family showing that subtilisins exploit the same catalytic triad as the

chymotrypsin Chymotrypsin (, chymotrypsins A and B, alpha-chymar ophth, avazyme, chymar, chymotest, enzeon, quimar, quimotrase, alpha-chymar, alpha-chymotrypsin A, alpha-chymotrypsin) is a digestive enzyme component of pancreatic juice acting in the duodenu ...

s although the residues occur in a different order (His/Asp/Ser in chymotrypsin and Asp/His/Ser in subtilisin); otherwise the structures show similarity to no other proteins. Some subtilisins are

mosaic protein A mosaic protein is a protein that is made up of different protein domains, giving the protein multiple functions. These proteins have quaternary structures, as they are made up of multiple tertiary structured protein domains. Protein domains can ...

s, whereas others contain N- and C-terminal extensions that show no sequence similarity to any other known protein. Based on

sequence homology 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 spe ...

, a subdivision into six families has been proposed. The proprotein-processing endopeptidases

kexin Kexin () is a prohormone-processing protease, specifically a yeast serine peptidase, found in the budding yeast (''S. cerevisiae''). It catalyzes the cleavage of -Lys-Arg- and -Arg-Arg- bonds to process yeast alpha-factor pheromone and killer to ...

furin Furin is a protease, a proteolytic enzyme that in humans and other animals is encoded by the ''FURIN'' gene. Some proteins are inactive when they are first synthesized, and must have sections removed in order to become active. Furin cleaves these s ...

and related enzymes form a distinct subfamily known as the kexin subfamily (S8B). These preferentially cleave C-terminally to paired basic amino acids. Members of this subfamily can be identified by subtly different motifs around the active site. Members of the kexin family, along with endopeptidases R, T and K from the yeast Tritirachium and cuticle-degrading peptidase from Metarhizium, require thiol activation. This can be attributed to the presence of Cys-173 near to the active histidine. Only 1 viral member of the subtilisin family is known, a 56-kDa protease from herpes virus 1, which infects the channel catfish. Sedolisins (serine-carboxyl peptidases) are proteolytic enzymes whose fold resembles that of subtilisin; however, they are considerably larger, with the mature catalytic domains containing approximately 375 amino acids. The defining features of these enzymes are a unique catalytic triad, Ser/Glu/Asp, as well as the presence of an aspartic acid residue in the oxyanion hole. High-resolution crystal structures have now been solved for sedolisin from Pseudomonas sp. 101, as well as for kumamolisin from a thermophilic bacterium, Bacillus novo sp. MN-32. Mutations in the human gene leads to a fatal neurodegenerative disease.

Human proteins containing this domain

FURIN Furin is a protease, a proteolytic enzyme that in humans and other animals is encoded by the ''FURIN'' gene. Some proteins are inactive when they are first synthesized, and must have sections removed in order to become active. Furin cleaves these s ...

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MBTPS1 Membrane-bound transcription factor site-1 protease, or site-1 protease (S1P) for short, also known as subtilisin/kexin-isozyme 1 (SKI-1), is an enzyme (EC 3.4.21.112) that in humans is encoded by the MBTPS1 gene. S1P cleaves the endoplasmic reti ...

;

PCSK1 Proprotein convertase 1, also known as prohormone convertase, prohormone convertase 3, or neuroendocrine convertase 1 and often abbreviated as PC1/3 is an enzyme that in humans is encoded by the ''PCSK1'' gene. PCSK1 and PCSK2 differentially clea ...

;

PCSK2 Proprotein convertase 2 (PC2) also known as prohormone convertase 2 or neuroendocrine convertase 2 (NEC2) is a serine protease and proprotein convertase PC2, like proprotein convertase 1 (PC1), is an enzyme responsible for the first step in the ma ...

;

PCSK4 Proprotein convertase subtilisin/kexin type 4 is an enzyme that in humans is encoded by the ''PCSK4'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meani ...

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PCSK5 Proprotein convertase subtilisin/kexin type 5 is an enzyme that in humans is encoded by the ''PCSK5'' gene, found in chromosome 9q21.3 Two alternatively spliced transcripts are described for this gene but only one has its full length nature known ...

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PCSK6 Proprotein convertase subtilisin/kexin type 6 is an protease that in humans is encoded by the ''PCSK6'' gene which is located in chromosome 15. Pcsk6 is a calcium-dependent serine endoprotease that catalyzes the post-translational modification of ...

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PCSK7 Proprotein convertase subtilisin/kexin type 7 is an enzyme that in humans is encoded by the ''PCSK7'' gene. The protein encoded by this gene belongs to the subtilisin-like proprotein convertase family. The members of this family are proprotein co ...

;

PCSK9 Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the ''PCSK9'' gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes (ortholog ...

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TPP2 Tripeptidyl-peptidase 2 is an enzyme that in humans is encoded by the ''TPP2'' gene. Among other things it is heavily implicated in MHC (HLA) class-I processing, as it has both endopeptidase and exopeptidase activity. Clinical significance and ge ...

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References

External links

* * * * {{Portal bar, Biology, border=no Protein domains Single-pass transmembrane proteins Proteases EC 3.4.21