ELIZA

return kwic search for function out of >500 occurrences
288503 occurrences (No.86 in the rank) during 5 years in the PubMed. [cache]

1) 826 missense variants demonstrated conserved inhibitory activity while 1137 resulted in loss of PAI-1 inhibitory function.

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PMID:34552126 DOI:10.1038/s41598-021-97871-7

2021 Scientific reports

* Deep mutational scanning of the plasminogen activator inhibitor-1 functional landscape.

- The serine protease inhibitor (SERPIN) plasminogen activator inhibitor-1 (PAI-1) is a key regulator of the fibrinolytic system, inhibiting the serine proteases tissue- and urokinase-type plasminogen activator (tPA and uPA, respectively). Missense variants render PAI-1 non-functional through misfolding, leading to its turnover as a protease substrate, or to a more rapid transition to the latent/inactive state. Deep mutational scanning was performed to evaluate the impact of amino acid sequence variation on PAI-1 inhibition of uPA using an M13 filamentous phage display system. Error prone PCR was used to construct a mutagenized PAI-1 library encompassing ~ 70% of potential single amino acid substitutions. The relative effects of 27% of all possible missense variants on PAI-1 inhibition of uPA were determined using high-throughput DNA sequencing. 826 missense variants demonstrated conserved inhibitory activity while 1137 resulted in loss of PAI-1 inhibitory function. The least evolutionarily conserved regions of PAI-1 were also identified as being the most tolerant of missense mutations. The results of this screen confirm previous low-throughput mutational studies, including those of the reactive center loop. These data provide a powerful resource for explaining structure-function relationships for PAI-1 and for the interpretation of human genomic sequence variants.

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[frequency of next (right) word to function]

(1)86 null	(9)5 following	(17)3 mutations	(25)2 for
(2)72 of	(10)5 was	(18)3 not	(26)2 have
(3)68 and	(11)5 with	(19)3 were	(27)2 including
(4)63 in	(12)4 by	(20)3 which	(28)2 measures
(5)16 is	(13)4 has	(21)2 after	(29)2 or
(6)13 as	(14)4 tests	(22)2 among	(30)2 quality
(7)5 are	(15)4 to	(23)2 data	(31)2 that
(8)5 associated	(16)3 at	(24)2 during	(32)2 variants

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--- WordNet output for function --- =>1.機能, 関数, 役割, 働き, 2.機能する, 作用する, 働く, 役目を果たす, 3.社交的会合, パーティー, 儀式 Overview of noun function The noun function has 7 senses (first 3 from tagged texts) 1. (43) function, mathematical function, single-valued function, map, mapping -- ((mathematics) a mathematical relation such that each element of a given set (the domain of the function) is associated with an element of another set (the range of the function)) 2. (24) function, purpose, role, use -- (what something is used for; "the function of an auger is to bore holes"; "ballet is beautiful but what use is it?") 3. (7) function, office, part, role -- (the actions and activities assigned to or required or expected of a person or group; "the function of a teacher"; "the government must do its part"; "play its role") 4. function -- (a relation such that one thing is dependent on another; "height is a function of age"; "price is a function of supply and demand") 5. function -- (a formal or official social gathering or ceremony; "it was a black-tie function") 6. affair, occasion, social occasion, function, social function -- (a vaguely specified social event; "the party was quite an affair"; "an occasion arranged to honor the president"; "a seemingly endless round of social functions") 7. routine, subroutine, subprogram, procedure, function -- (a set sequence of steps, part of larger computer program) Overview of verb function The verb function has 3 senses (first 3 from tagged texts) 1. (9) function, work, operate, go, run -- (perform as expected when applied; "The washing machine won't go unless it's plugged in"; "Does this old car still run well?"; "This old radio doesn't work anymore") 2. (3) serve, function -- (serve a purpose, role, or function; "The tree stump serves as a table"; "The female students served as a control group"; "This table would serve very well"; "His freedom served him well"; "The table functions as a desk") 3. (1) officiate, function -- (perform duties attached to a particular office or place or function; "His wife officiated as his private secretary") --- WordNet end ---