Kertailtu sinkkiproteiinien lueteloa. ZNHIT geenejä on kuusi

 ZNHIT geeniryhmä. Onko siitä jotain uutista ? Katsotaan. 

Tässä on  n. 20 v  vanha artikkeli ajoista, kun HIT-motiivin  sinkkisormiproteiinin funktiota alettiin hahmottaa. eri yhteyksistä. Kysyin  suomeksi AI:lta ja sain hyvän ja valaisevan  vastauksen, mutta koska on keskiyö, jatkan noteerausta myöhemmin.  Tiedettiin, ettei ne säädä DNA:ta suoraan ja että niiden sinkkisormirakennelma on ainutlaatuinen. 

A zinc finger HIT domain-containing protein, ZNHIT-1, interacts with orphan nuclear hormone receptor Rev-erbbeta and removes Rev-erbbeta-induced inhibition of apoCIII transcription

Jiadong Wang 1, Yang Li, Min Zhang, Zhongle Liu, Cong Wu, Hanying Yuan, Yu-Yang Li, Xin Zhao, Hong Lu

Affiliations 

• PMID: 17892483
• DOI: 10.1111/j.1742-4658.2007.06062.x

ZNF LIM-tyyppiset sinkkisormiproteiinit (53 geeniä) joista mainitaan 4 alaryhmää

 LIM domain LIM domains are protein structural domains, composed of two contiguous zinc finger domains, separated by a two- amino acid residue hydrophobic linker. They are named after their initial discovery in the proteins L in11, I sl-1 & M ec-3.

Group contains the following subgroups 

• LIM class homeoboxes 12 genes 
• Ajuba family 3 genes 

• LIMS zinc finger family (LIMS) 4 genes 
• Zyxin family 3 genes
• 
  

ZNF PCLO- tyyppiset, 2 geeniä, piccolo-tyyppiset sinkkisormet

 Zinc fingers, piccolo-type Piccolo zinc fingers were found to interact with the dual prenylated rab3A and VAMP2/Synaptobrevin II receptor PRA1. There are eight conserved cysteines in Piccolo-type zinc fingers, suggesting that they coordinate two zinc ligands. [Source: InterPro] 

ZNF TRAF-tyyppiset. 13 jäsentä ryhmässä (HUGO)

 Zinc fingers, TRAF-type This gene group contains genes that encode proteins with a TRAF-type zinc finger domain. Some of the proteins that have this domain are mammalian signal transducers associated with the cytoplasmic domain of the 75kDa tumour necrosis factor receptor. A heterocomplex, homodimer or heterodimer of TRAF1 and TRAF2, binds to the N-terminal of the inhibitor of apoptosis proteins 1 and 2 (IAPS) and recruits them to the tumour necrosis factor receptor 2. [Source: InterPro]

 Genes contained within the group: 13

Tarkistan sinkkisormiproteiinien HUGO ryhmät nyt 11.2.2026. Poimin esiin uusia nimettyjä tai lisättyjä ryhmiä)

 

Group contains the following subgroups 

• LIM domain containing
• GATA zinc finger domain containing (GATAD)
• Nuclear hormone receptors (NR)
• PHD finger proteins (PHF)
• Ring finger proteins (RNF)
• THAP domain family (THAP)
• Zinc fingers AN1-type (ZFAND)
• Zinc fingers A20-type
• Zinc fingers BED-type (ZBED)
• Zinc fingers CCCH-type (ZC3H)
• Zinc fingers CCHC-type (ZCCHC)
• Zinc fingers CW-type (ZCW)
• Zinc fingers C2HC-type (ZC2HC)
• Zinc fingers C2H2-type (ZNF)
• Zinc fingers C2H2C-type
• Zinc fingers DBF-type (ZDBF)
• Zinc fingers DHHC-type (ZDHHC)
• Zinc fingers FYVE-type (ZFYVE)
• Zinc fingers GRF-type (ZGRF)
• Zinc fingers HIT-type (ZNHIT)
• Zinc fingers matrin-type (ZMAT)
• Zinc fingers MIZ-type (ZMIZ)
• Zinc fingers MYM-type (ZMYM)
• Zinc fingers MYND-type (ZMYND)
• Zinc fingers NFX1-type
• Zinc fingers PARP-type
• Zinc fingers PCLO-type
• Zinc fingers RANBP2-type (ZRANB)
• Zinc fingers SWIM-type (ZSWIM)
• Zinc fingers TRAF-type
• Zinc fingers U11-48K-like CHHC-type
• Zinc fingers ZZ-type (ZZZ)
• Zinc fingers 3CxxC-type (Z3CXXC)
• Zinc fingers CXXC-type (CXXC)

UBOX6 omaa rakenteessan myös WD 7-blade propellin ja tunnetaan ,WD reoeat, SAM ja UBOX domeenit omaavana ubikitiiniligasina

 Suoranaisesti  vaikea löytää nmellä UBOX6, mutta  ainakin  geeninimellä WDSUB1  voi löytää. 

Domeeninimi SAM on lyhennys sanoista Sterile Alpha Motif. 

Olen keräämässä listäää U-Box  E3 ligaaseista ja ainakaan ei ole U-BOX7 numeroista vielä  löytynyt. 

https://www.genecards.org/cgi-bin/carddisp.pl?gene=WDSUB1&keywords=WDSAM1

Uusi UBOX perheenjäsen UBOX4 Geenin virallinen nimi PRPF19, Pre-mRNA processing factor 19

 

Aliases for PRPF19 Gene

• GeneCards Symbol: PRPF19 ²
• Pre-MRNA Processing Factor 19 ^{2 3 5}
• NMP200 ^{2 3 4 5}
• SNEV ^{2 3 4 5}
• UBOX4 ^{2 3 5}
• HPSO4 ^{2 3 5}
• PRP19 ^{3 4 5}
• PSO4 ^{2 3 5}
• Nuclear Matrix Protein NMP200 Related To Splicing Factor PRP19 ^{2 3}
• RING-Type E3 Ubiquitin Transferase PRP19 ^{3 4}

• Pre-MRNA-Processing Factor 19 ^{3 4}
• Nuclear Matrix Protein 200 ^{3 4}
• Senescence Evasion Factor ^{3 4}
• PRP19/PSO4 Homolog ^{3 4}
• Psoralen 4 ^{2 3}
• PRP19/PSO4 Pre-MRNA Processing Factor 19 Homolog (S. Cerevisiae) ²
• PRP19/PSO4 Pre-MRNA Processing Factor 19 Homolog ³
• PRP19/PSO4 Homolog (S. Cerevisiae) ²
• EC 2.3.2.27 ⁴
• HPso4 
•  

Deubikitinaasi OTUD4 rekrytoi USP9X ja USP7 avukseen esim. DNA:n alkylaatiovaurion korjaukseen.

USP9X  (Kr. Xp11.4)  

(2554 aminoacid)

Recommended name: Ubiquitin carboxyl-terminal hydrolase 9X

Aliases: 

• GeneCards Symbol: USP9X ²
• Ubiquitin Specific Peptidase 9 X-Linked ^{2 3 5}
• DFFRX ^{2 3 4 5}
• FAF-X ^{2 3 5}
• MRX99 ^{2 3 5}
• FAF ^{2 3 5}
• Ubiquitin Specific Protease 9, X Chromosome (Fat Facets-Like Drosophila) ^{2 3}
• Ubiquitin-Specific Protease 9, X Chromosome ^{3 4}
• Ubiquitin Carboxyl-Terminal Hydrolase 9X ^{3 4}
• Deubiquitinating Enzyme FAF-X ³  
• Ubiquitin Thioesterase FAF-X ^{3 4}
• Fat Facets-Like, X-Linked ^{2 3}
• Fat Facets In Mammals ^{3 4}
• HFAM ^{3 4}
• FAM ^{3 4}
• etc
  

 https://www.genecards.org/cgi-bin/carddisp.pl?gene=USP9X&keywords=ubiquitin-specific,protease,X,9

This gene is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases (USPs). Though this gene is located on the X chromosome, it escapes X-inactivation. Mutations in this gene have been associated with Turner syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Molecular function for USP9X Gene according to UniProtKB/Swiss-Prot

Function:

• Deubiquitinase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins (PubMed:18254724, 19135894, 22371489, 25944111, 29626158, 30914461, 37454738).
  May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin (PubMed:18254724, 19135894, 22371489, 25944111, 29626158, 30914461, 37454738).
  Specifically hydrolyzes 'Lys-11'-, followed by 'Lys-63'-, 'Lys-48'- and 'Lys-6'-linked polyubiquitins chains (PubMed:30914461).
  Essential component of TGF-beta/BMP signaling cascade (PubMed:19135894).
  Specifically deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33 (PubMed:19135894).
  Deubiquitinates alkylation repair enzyme ALKBH3 (PubMed:25944111).
• 
  OTUD4 recruits USP7 and  1 to stabilize ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111). OTUD4 is a scaffold for USP7 and USP9X, two deubiquitinases that act directly on the AlkB proteins. Moreover, we show that loss of OTUD4, USP7, or USP9X in tumor cells makes them significantly more sensitive to alkylating agents. Taken together, this work reveals a novel, noncanonical mechanism by which an OTU family deubiquitinase regulates its substrates, and provides multiple new targets for alkylation chemotherapy sensitization of tumors. 
•  
•  Deubiquitinates RNA demethylase enzyme ALKBH5, promoting its stability (PubMed:37454738).
  
  2023 Aug;299(8):105055.doi: 10.1016/j.jbc.2023.105055. Epub 2023 Jul 15.
  Deubiquitinase USP9X stabilizes RNA m⁶A demethylase ALKBH5 and promotes acute myeloid leukemia cell survival 
   
  Deubiquitinates mTORC2 complex component RICTOR at 'Lys-294' by removing 'Lys-63'-linked polyubiquitin chains, stabilizing RICTOR and enhancing its binding to MTOR, thus promoting mTORC2 complex assembly (PubMed:33378666).The mechanistic target of rapamycin complex 2 (mTORC2) controls cell metabolism and survival in response to environmental inputs. Dysregulation of mTORC2 signaling has been linked to diverse human diseases, including cancer and metabolic disorders, highlighting the importance of a tightly controlled mTORC2...Here, we present data, from human cell lines and mice, describing a mechanism by which growth factors regulate ubiquitin-specific protease 9X (USP9X) deubiquitinase to stimulate mTORC2 assembly and activity. USP9X removes Lys63-linked ubiquitin from RICTOR to promote its interaction with mTOR, thereby facilitating mTORC2 signaling. As mTORC2 is central for cellular homeostasis, understanding the mechanisms regulating mTORC2 activation toward its downstream targets is vital for our understanding of physiological processes and for developing new therapeutic strategies in pathology.
• 
  Regulates chromosome alignment and segregation in mitosis by regulating the localization of BIRC5/survivin to mitotic centromeres (PubMed:16322459)...Proper chromosome segregation requires the attachment of sister kinetochores to microtubules from opposite spindle poles to form bi-oriented chromosomes on the metaphase spindle. The chromosome passenger complex containing Survivin and the kinase Aurora B regulates this process from the centromeres. We report that a de-ubiquitinating enzyme, hFAM, regulates chromosome alignment and segregation by controlling both the dynamic association of Survivin with centromeres and the proper targeting of Survivin and Aurora B to centromeres. Survivin is ubiquitinated in mitosis through both Lys(48) and Lys(63) ubiquitin linkages. Lys(63) de-ubiquitination mediated by hFAM is required for the dissociation of Survivin from centromeres, whereas Lys(63) ubiquitination mediated by the ubiquitin binding protein Ufd1 is required for the association of Survivin with centromeres. Thus, ubiquitinaton regulates dynamic protein-protein interactions and chromosome segregation independently of protein degradation. 
• 
  Involved in axonal growth and neuronal cell migration (PubMed:24607389). Loss of Usp9x causes reduction in both axonal growth and neuronal cell migration.
• 
  Regulates cellular clock function by enhancing the protein stability and transcriptional activity of the core circadian protein BMAL1 via its deubiquitinating activity (PubMed:29626158).Living organisms on the earth maintain a roughly 24 h circadian rhythm, which is regulated by circadian clock genes and their protein products. Post-translational modifications of core clock proteins could affect the circadian behavior. Although ubiquitination of core clock proteins was studied extensively, the reverse process, deubiquitination, has only begun to unfold and the role of this regulation on circadian function is not completely understood. Here, we use affinity purification and mass spectrometry analysis to identify probable ubiquitin carboxyl-terminal hydrolase FAF-X (USP9X) as an interacting protein of the core clock protein aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL or BMAL1). Through biochemical experiments, we discover that USP9X reduces BMAL1 ubiquitination, enhances its stability, and increases its protein level, leading to the elevated transcriptional activity. Bioluminescence measurement reveals that USP9X knockdown decreases the amplitude of the cellular circadian rhythm but the period and phase are not affected. Our experiments find a new regulator for circadian clock at the post-translational level and demonstrate a different regulatory function for the circadian clock through the deubiquitination and the up-regulation of the core clock protein BMAL1 in the positive limb of the transcription-translation feedback loop.
• 
  Acts as a regulator of peroxisome import by mediating deubiquitination of PEX5: specifically deubiquitinates PEX5 monoubiquitinated at 'Cys-11' following its retrotranslocation into the cytosol, resetting PEX5 for a subsequent import cycle (PubMed:22371489).Peroxin 5 (PEX5), the peroxisomal protein shuttling receptor, binds newly synthesized peroxisomal matrix proteins in the cytosol and promotes their translocation across the organelle membrane. During the translocation step, PEX5 itself becomes inserted into the peroxisomal docking/translocation machinery. PEX5 is then monoubiquitinated at a conserved cysteine residue and extracted back into the cytosol in an ATP-dependent manner. We have previously shown that the ubiquitin-PEX5 thioester conjugate (Ub-PEX5) released into the cytosol can be efficiently disrupted by physiological concentrations of glutathione, raising the possibility that a fraction of Ub-PEX5 is nonenzymatically deubiquitinated in vivo.,,,ubiquitin-specific protease 9X (USP9X) is by far the most active deubiquitinase acting on Ub-PEX5, ...USP9X is an elongated monomeric protein with the capacity to hydrolyze thioester, isopeptide, and peptide bonds.
  Deubiquitinates PEG10 (By similarity).
• 
  Inhibits the activation of the Hippo signaling pathway via deubiquitination of AMOTL2 at 'Lys-347' and 'Lys-408' which prohibits its interaction with and activation of LATS2.
  Loss of LATS2 activation and subsequent loss of YAP1 phosphorylation results in an increase in YAP1-driven transcription of target genes (PubMed:26598551, 34404733). LATS1/2 (large tumor suppressor) kinases and the Angiomotin family proteins are potent inhibitors of the YAP (yes-associated protein) oncoprotein, but the underlying molecular mechanism is not fully understood. Here, we report for the first time that USP9X is a deubiquitinase of Angiomotin-like 2 (AMOTL2) and that AMOTL2 mono-ubiquitination is required for YAP inhibition. USP9X_HUMAN,Q93008

CatalyticActivity:

Deubikitinaasi USPX9/SolusykliCDC123 -akseli edistää rintasyöpääj säätelemällä solusykliä.

 

. 2023 Oct;62(10):1487-1503.

doi: 10.1002/mc.23591. Epub 2023 Jun 14.

USP9X deubiquitinates and stabilizes CDC123 to promote breast carcinogenesis through regulating cell cycle

Nan Song  ¹ , Ling Deng  ¹ , Lijie Zeng  ¹ , Li He  ¹ , Chunyan Liu  ¹ , Ling Liu  ¹ , Rong Fu  ¹

Affiliations

• PMID: 37314216
• DOI: 10.1002/mc.23591

Abstract

Cell division cycle 123 (CDC123) has been implicated in a variety of human diseases. However, it remains unclear whether CDC123 plays a role in tumorigenesis and how its abundance is regulated. In this study, we found that CDC123 was highly expressed in breast cancer cells, and its high expression was positively correlated with a poor prognosis. Knowndown of CDC123 impaired the proliferation of breast cancer cells. Mechanistically, we identified a deubiquitinase, ubiquitin-specific peptidase 9, X-linked (USP9X), that could physically interact with and deubiquitinate K48-linked ubiquitinated CDC123 at the K308 site. Therefore, the expression of CDC123 was positively correlated with USP9X in breast cancer cells. In addition, we found that deletion of either USP9X or CDC123 led to altered expression of cell cycle-related genes and resulted in the accumulation of cells population in the G0/G1 phase, thereby suppressing cell proliferation. Treatment with the deubiquitinase inhibitor of USP9X, WP1130 (Degrasyn, a small molecule compound that USP9X deubiquitinase inhibitor), also led to the accumulation of breast cancer cells in the G0/G1 phase, but this effect could be rescued by overexpression of CDC123. Furthermore, our study revealed that the USP9X/CDC123 axis promotes the occurrence and development of breast cancer through regulating the cell cycle, and suggests that it may be a potential target for breast cancer intervention. In conclusion, our study demonstrates that USP9X is a key regulator of CDC123, providing a novel pathway for the maintenance of CDC123 abundance in cells, and supports USP9X/CDC123 as a potential target for breast cancer intervention through regulating the cell cycle.

Keywords: CDC123; USP9X; breast cancer; deubiquitination; protein stability.

© 2023 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.

PubMed Disclaimer

Similar articles

• Deubiquitinase ubiquitin-specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells.

  Lu Q, Lu D, Shao ZM, Li DQ. Cancer Sci. 2019 Apr;110(4):1268-1278. doi: 10.1111/cas.13953. Epub 2019 Feb 21. PMID: 30689267 Free PMC article.Collectively, these findings indicate that USP9X is a stabilizer of RNF115 protein and that the USP9X-RNF115 signaling axis is implicated in the breast cancer malignant phenotype.
• USP9X-mediated deubiquitination of B-cell CLL/lymphoma 9 potentiates Wnt signaling and promotes breast carcinogenesis.

  Shang Z, Zhao J, Zhang Q, Cao C, Tian S, Zhang K, Liu L, Shi L, Yu N, Yang S. J Biol Chem. 2019 Jun 21;294(25):9844-9857. doi: 10.1074/jbc.RA119.007655. Epub 2019 May 9. PMID: 31073027 Free PMC article.
• USP9X regulates centrosome duplication and promotes breast carcinogenesis.

  Li X, Song N, Liu L, Liu X, Ding X, Song X, Yang S, Shan L, Zhou X, Su D, Wang Y, Zhang Q, Cao C, Ma S, Yu N, Yang F, Wang Y, Yao Z, Shang Y, Shi L. Nat Commun. 2017 Mar 31;8:14866. doi: 10.1038/ncomms14866. PMID: 28361952 Free PMC article.

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]