SOLUSYKLI

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:

torsdag 16 januari 2025

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 Song¹, Ling Deng¹, Lijie Zeng¹, Li He¹, Chunyan Liu¹, Ling Liu¹, Rong Fu¹

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.

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fredag 22 mars 2024

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]

SERPINB5, MASPIN, normaalisti estää rintasyövän kasvua, invaasiota ja metastasoitumista

MASPIN in Cancer , PubMed Search:

https://pubmed.ncbi.nlm.nih.gov/?term=MASPIN++in+cancer&sort=date

741 results

GeneCards:

SERPIN B5, Maspin , https://www.genecards.org/cgi-bin/carddisp.pl?gene=SERPINB5&keywords=MASPIN

18q21.33 , Suositeltu proteiinin nimi, Recommended name: SERPIN B5

Protein attributes for SERPINB5 Gene

Size: 375 amino acids
Molecular mass:42100 Da
Quaternary structure: Interacts with IRF6.

Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be involved in negative regulation of endopeptidase activity. Predicted to act upstream of or within several processes, including extracellular matrix organization; prostate gland morphogenesis; and regulation of epithelial cell proliferation. Located in cytoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

GeneCards Summary for SERPINB5 Gene

SERPINB5 (Serpin Family B Member 5) is a Protein Coding gene. Diseases associated with SERPINB5 include Pleomorphic Adenoma and Bone Squamous Cell Carcinoma. Among its related pathways are Validated transcriptional targets of TAp63 isoforms and Apoptosis and Autophagy. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity. An important paralog of this gene is SERPINB1.

UniProtKB/Swiss-Prot Summary for SERPINB5 Gene

Tumor suppressor. It blocks the growth, invasion, and metastatic properties of mammary tumors. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity. ( SPB5_HUMAN,P36952 )

Molecular function for SERPINB5 Gene according to UniProtKB/Swiss-Prot

Function:

Tumor suppressor.
It blocks the growth, invasion, and metastatic properties of mammary tumors.
As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity. SPB5_HUMAN,P36952

Molecular function for SERPINB5 Gene according to GENATLAS

Biochemistry:

tumor suppressor of breast and prostate carcinomas,inhibiting tumor motility,invasion and metastasis,expressed by a number of cell types of epithelial cells,located in the cell membrane and extracellular matrix,serine proteinase inhibitor,member of the serpin family,ovalbumin subgroup SERPINB5

SERPIN B5, (String kartan molekyylit)

Interacting Proteins for SERPINB5 Gene

STRING Interaction Network Preview (showing top 5 STRING interactants - click image to see top 25)

Your Current Organism:

Homo sapiens

NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man

Your Input:
	SERPINB5	Serpin B5; Tumor suppressor. It blocks the growth, invasion, and metastatic properties of mammary tumors. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity; Belongs to the serpin family. Ov-serpin subfamily. (375 aa)
	HDAC1	Histone deacetylase 1; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium st [...] (482 aa)
	PPIL3	Peptidyl-prolyl cis-trans isomerase-like 3; PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. May be involved in pre-mRNA splicing; Belongs to the cyclophilin-type PPIase family. PPIL3 subfamily. (165 aa)
	LACC1	Laccase domain-containing protein 1; Central regulator of the metabolic function and bioenergetic state of macrophages. In macrophages, promotes flux through de novo lipogenesis to concomitantly drive high levels of both fatty-acid oxidation and glycolysis. (430 aa)
	C11orf54	Ester hydrolase C11orf54; Exhibits ester hydrolase activity on the substrate p- nitrophenyl acetate. (315 aa)
	HMGCS1	Hydroxymethylglutaryl-CoA synthase, cytoplasmic; This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase. (520 aa)
	GPR18	N-arachidonyl glycine receptor; Receptor for endocannabinoid N-arachidonyl glycine (NAGly). However, conflicting results about the role of NAGly as an agonist are reported. Can also be activated by plant-derived and synthetic cannabinoid agonists. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. May contribute to regulation of the immune system. Is required for normal homeostasis of CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs)in small intstine by supporting preferential migration of CD8alphaalpha T-cells [...] (331 aa)
	EIF2A	Eukaryotic translation initiation factor 2A, N-terminally processed; Functions in the early steps of protein synthesis of a small number of specific mRNAs. Acts by directing the binding of methionyl- tRNAi to 40S ribosomal subunits. In contrast to the eIF-2 complex, it binds methionyl-tRNAi to 40S subunits in a codon-dependent manner, whereas the eIF-2 complex binds methionyl-tRNAi to 40S subunits in a GTP-dependent manner; Belongs to the WD repeat EIF2A family. (585 aa)
	VRK1	Serine/threonine-protein kinase VRK1; Serine/threonine kinase involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Acts by mediating phosphorylation of downstream target protein. Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates casein and histone H3. Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain- containing proteins and causes its relocalization from the nucleus to the cytoplasm. Phosph [...] (396 aa)
	KAT7	Histone acetyltransferase KAT7; Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Involved in H3K14 (histone H3 lysine 14) acetylation and cell proliferation (By similarity). Through chromatin acetylation it may regulate DNA replication and act as a coactivator of TP53-dependent transcription. Acts as a coactivator of the licensing factor CDT1. Specifically represses AR-mediated transcription. Belongs to the MYST (SAS/MOZ) family. (611 aa)
	CALML5	Calmodulin-like protein 5; Binds calcium. May be involved in terminal differentiation of keratinocytes. (146 aa)
	BLMH	Bleomycin hydrolase; The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B- aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity. (455 aa)
	NAA50	N-alpha-acetyltransferase 50; N-alpha-acetyltransferase that acetylates the N-terminus of proteins that retain their initiating methionine. Has a broad substrate specificity: able to acetylate the initiator methionine of most peptides, except for those with a proline in second position. Also displays N-epsilon-acetyltransferase activity by mediating acetylation of the side chain of specific lysines on proteins. Autoacetylates in vivo. The relevance of N-epsilon-acetyltransferase activity is however unclear: able to acetylate H4 in vitro, but this result has not been confirmed in vivo. [...] (169 aa)
	PKP1	Plakophilin-1; Seems to play a role in junctional plaques. Contributes to epidermal morphogenesis. (747 aa)
	LGALS7B	Galectin-7; Could be involved in cell-cell and/or cell-matrix interactions necessary for normal growth control. Pro-apoptotic protein that functions intracellularly upstream of JNK activation and cytochrome c release. (136 aa)
	SYT16	Synaptotagmin-16; May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Is Ca(2+)-independent. (645 aa)
	CCDC82	Coiled-coil domain containing 82. (544 aa)
	RBM24	RNA-binding protein 24; Multifunctional RNA-binding protein involved in the regulation of pre-mRNA splicing, mRNA stability and mRNA translation important for cell fate decision and differentiation. Plays a major role in pre-mRNA alternative splicing regulation. Mediates preferentially muscle-specific exon inclusion in numerous mRNAs important for striated cardiac and skeletal muscle cell differentiation. Binds to intronic splicing enhancer (ISE) composed of stretches of GU-rich motifs localized in flanking intron of exon that will be included by alternative splicing (By similarity). I [...] (236 aa)
	ALDH2	Aldehyde dehydrogenase, mitochondrial; Aldehyde dehydrogenase 2 family member; Belongs to the aldehyde dehydrogenase family. (517 aa)
	COL1A2	Collagen alpha-2(I) chain; Type I collagen is a member of group I collagen (fibrillar forming collagen); Belongs to the fibrillar collagen family. (1366 aa)
	UCHL5	Ubiquitin carboxyl-terminal hydrolase isozyme L5; Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1. (355 aa)
	PRSS21	Testisin; Could regulate proteolytic events associated with testicular germ cell maturation. (314 aa)
	CUL9	Cullin-9; Core component of a Cul9-RING ubiquitin-protein ligase complex, a complex that mediates ubiquitination and subsequent degradation of BIRC5 and is required to maintain microtubule dynamics and genome integrity. Acts downstream of the 3M complex, which inhibits CUL9 activity, leading to prevent ubiquitination of BIRC5. Cytoplasmic anchor protein in p53/TP53-associated protein complex. Regulates the subcellular localization of p53/TP53 and subsequent function. (2517 aa)
	TRIM21	E3 ubiquitin-protein ligase TRIM21; E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is used not only for the ubiquitination of USP4 and IKBKB but also for its self-ubiquitination. Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes. A TRIM21-containing SCF(SKP2)-like complex is shown to mediate ubiquitination of CDKN1B ('Thr-187' phosphorylated-form), thereby promoting its degrad [...] (475 aa)
	AKIRIN2	Akirin-2; Required for the innate immune response. Downstream effector of the Toll-like receptor (TLR), TNF and IL-1 beta signaling pathways leading to the production of IL-6. Forms a complex with YWHAB that acts to repress transcription of DUSP1 (By similarity); Belongs to the akirin family. (203 aa)
	BRD4	Bromodomain-containing protein 4; Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure. During interphase, plays a key role in regulating the transcription of signal- inducible genes by associating with the P-TEFb complex and re [...] (1362 aa)

Kaavaa sinkkiproteaasi superperheestä, johon kuuluvat MMP, matrixmetalloproteinaasit

Zn proteaasien superperhe

GLUZINCIN

INUZINCIN

METZINCIN

CARBOXYPEPTIDASE

DDCARBOXY

METZINCIN
genefamily https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036576/

MATRIXIN:

Matrixmetalloproteases MMPs, ( Tissue Inhibitors of MMP = TIMPs)

ASTACIN:https://www.frontiersin.org/articles/10.3389/fmolb.2022.1080836/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848320/

Meprin

BMP1/TII

ADAMALYSIN:

ADAM

ADAMTS

Class III Snake Venoms

SERRALYSIN

SOLUSYKLI

Leta i den här bloggen

måndag 15 december 2025

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

måndag 10 november 2025

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

Aliases for PRPF19 Gene

fredag 17 januari 2025

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