Serpiinit, seriiniproteaasi-inhibiittorit

 Seriiniproteaasi-inhibiittori lääkkeissä on Trasylol. aprotiniini. Sitä  joudutaan käyttämään sydämen ohituksleikkauksissa kun on hallittava verenkierron rheologiassa tapahtuvia  suuria muutoksia proteolyyttisiä aktivaatioita : Pancreatic Trypsin Inhibitor Trasylol Trypsin inhibitor

 Näistä vahvoista  proteaaseista  löydettiin  ensimmäiset serpiinit ja siksi nimi seriiniproteaasi-inhibiittorit, serpins, mutta  osa serpiinirakenteisista ei ole  inhibitorisia. Niitä on  luomakunnassa erittäinpaljon. Ihmisille tyypilliset on taulukoitu  kirjaiminja numeroin sitä muiaa kun niitä löydettiin. 

Kaikki  serpiinit eivät kuitenkaan ole proteaasi-inhibiittoreita  luonteeltaan ja niiden ominaisuuksiakin on  taulukoitu . Ensimmäiset löydetyt olivat   reologian alueen serpiineitä.

• Uusia tietoja  eri serpiineistä Pub Med artikkeleissa 2024: 
  

 https://en.wikipedia.org/wiki/Serpin

SERPIN E1,  PAI-1  https://pubmed.ncbi.nlm.nih.gov/38500661/

SERPIN E2,   PI7, Protease nexin 1   https://pubmed.ncbi.nlm.nih.gov/38407942/  Kay role in many tumors, lever ca metastases) ...SERPINE2 activated epidermal growth factor receptor (EGFR) and its downstream signaling pathways by interacting with EGFR. Mechanistically, SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase, c-Cbl. Additionally, EGFR was activated in liver cancer cells after sorafenib treatment, and SERPINE2 knockdown-induced EGFR downregulation significantly enhanced the therapeutic efficacy of sorafenib against liver cancer. Furthermore, we found that SERPINE2 knockdown also had a sensitizing effect on lenvatinib treatment.

 SERPIN F1, PEDF:  https://pubmed.ncbi.nlm.nih.gov/38474001/

SERPIN B5, Maspin:  https://pubmed.ncbi.nlm.nih.gov/38509770/

https://pubmed.ncbi.nlm.nih.gov/8290962/

SERPIN B9 ,PI9, Cytoplasmic Anti-Proteinase 9 , CAP9, ( intracellular inhibitor of granzyme B) 

SERPIN B12, Yokopin  https://pubmed.ncbi.nlm.nih.gov/38504347/

 2024 mainitaan SERBP1, SERPIN mRNA-binding protein 1 https://pubmed.ncbi.nlm.nih.gov/38408537/

https://genomebiology.biomedcentral.com/articles/10.1186/gb-2006-7-5-216/tables/1 

Table 1 Function and dysfunction of human serpins

From: An overview of the serpin superfamily

Serpin	Alternative name(s)	Protease target or function	Involvement in disease
SERPINA1	Antitrypsin	Extracellular; inhibition of neutrophil elastase	Deficiency results in emphysema: polymerization and retention in the ER results in cirrhosis [14,64,65]
SERPINA2	Antitrypsin-related protein	Not characterized, probable pseudogene
SERPINA3	Antichymotrypsin	Extracellular; inhibition of cathepsin G	Deficiency results in emphysema (see [61] for a review)
SERPINA4	Kallistatin (PI4)	Extracellular, inhibition of kallikrein [68]
SERPINA5	Protein C inhibitor (PAI-3)	Extracellular; inhibition of active protein C (see [69] for a review)	Angioedema
SERPINA6	Corticosteroid-binding globulin	Extracellular; non-inhibitory; cortisol binding	Deficiency linked to chronic fatigue [83,84]
SERPINA7	Thyroxine-binding globulin	Extracellular; non-inhibitory, thyroxine binding	Deficiency results in hypothyroidism [85]
SERPINA8	Angiotensinogen	Extracellular; non-inhibitory; amino-terminal cleavage by the protease renin results in release of the decapeptide angiotensin I	Certain variants linked to essential hypertension [86]
SERPINA9	Centerin	Extracellular; maintenance of naive B cells [70]
SERPINA10	Protein Z-dependent proteinase inhibitor	Extracellular; inhibition of activated factor Z and XI	Deficiency linked to venous thromboembolic disease [87]
SERPINA11	XP_170754.3	Not characterized
SERPINA12	Vaspin	Extracellular; insulin-sensitizing adipocytokine [71]
SERPINA13	XM_370772	Not characterized
SERPINB1	Monocyte neutrophil elastase inhibitor	Intracellular; inhibition of neutrophil elastase [72]
SERPINB2	Plasminogen activator inhibitor-2 (PAI2)	Intracellular; inhibition of uPA (see [73] for a review)
SERPINB3	Squamous cell carcinoma antigen-1	Intracellular; cross-class inhibition of cathepsins L and V [6]
SERPINB4	Squamous cell carcinoma antigen-2	Intracellular; cross-class inhibition of cathepsin G and chymase [74]
SERPINB5	Maspin	Intracellular; non-inhibitory; inhibition of metastasis through uncharacterized mechanism	Downregulation and/or intracellular location linked to tumor progression and overall prognosis [10]
SERPINB6	Proteinase inhibitor-6 (PI6)	Intracellular, inhibition of cathepsin G [75]
SERPINB7	Megsin	Intracellular; megakaryocyte maturation [76]	IgA nephropathy
SERPINB8	Cytoplasmic antiproteinase 8 (PI8)	Intracellular; inhibition of furin [77]
SERPINB9	Cytoplasmic antiproteinase 9 (PI9)	Intracellular, inhibition of granzyme B [78]
SERPINB10	Bomapin (PI10)	Intracellular; inhibition of thrombin and trypsin [79]
SERPINB11	Epipin	Intracellular
SERPINB12	Yukopin	Intracellular; inhibition of trypsin [80]
SERPINB13	Headpin (PI13)	Intracellular; inhibition of cathepsins L and K
SERPINC1	Antithrombin	Extracellular; thrombin and factor Xa inhibitor	Deficiency results in thrombosis (see [88] for review)
SERPIND1	Heparin cofactor II	Extracellular; thrombin inhibitor	May contribute to thrombotic risk when combined with other deficiencies [89]
SERPINE1	Plasminogen activator inhibitor I (PAI1)	Extracellular; inhibitor of thrombin, uPA, tPA and plasmin	Abnormal bleeding [90]
SERPINE2	Protease nexin I (PI7)	Extracellular; inhibition of uPA and tPA
SERPINE3	Hs.512272	Not characterized
SERPINF1	Pigment epithelium derived factor	Non-inhibitory; potent anti-angiogenic molecule [81]
SERPINF2	Alpha-2-antiplasmin	Extracellular; plasmin inhibitor	Unrestrained fibrinolytic activity, bleeding [91]
SERPING1	C1 inhibitor	C1 esterase inhibitor	Angioedema [92]
SERPINH1	47kDa heat-shock protein	Non-inhibitory molecular Chaperone for collagens [9]
SERPINI1	Neuroserpin (PI12)	Extracellular; inhibitor of tPA, uPA and plasmin	Polymerization results in dementia [17]
SERPINI2	Myoepithelium-derived serine proteinase inhibitor (PI14)	Extracellular; inhibition of cancer metastasis [82]