P57080

SS
Gene name
Usp25
Protein name
Ubiquitin carboxyl-terminal hydrolase 25
Names
EC 3.4.19.12 , Deubiquitinating enzyme 25 , Ubiquitin thioesterase 25 , Ubiquitin-specific-processing protease 25 , mUSP25
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:30940
EC number
3.4.19.12: Omega peptidases
Protein Class

Descriptions

Ubiquitin carboxyl-terminal hydrolase 25 (USP25) is a deubiquitinating enzyme and plays a major role in the regulation of the innate immune response, in auto-immunity and in tumorigenesis, through interactions with different tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins. USP25 possesses a Ub-associated domain (UBA), two Ub-interacting motifs (UIMs), an N-terminal catalytic domain (USP), and an unknown folded C-terminal part. USP25 presents an autoinhibited tetramer through the interaction of the USP25 catalytic domain inserted domain (UCID) of one dimer with the catalytic domains (ubiquitin carboxyl-terminal hydrolase) of the other dimer and vice versa, thereby creating a tetrahedrally shaped assembly. The activation of USP25 is not achieved through substrate or ubiquitin binding and may require an unknown activator.

Autoinhibitory domains (AIDs)

465-538 (USP25 catalytic domain inserted domain, UCID) SS

Target domain

169-655 (Ubiquitin carboxyl-terminal hydrolase)

Relief mechanism

Others

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

2 structures for P57080

Entry ID Method Resolution Chain Position Source
1VDL NMR - A 1-67 PDB
AF-P57080-F1 Predicted AlphaFoldDB

23 variants for P57080

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389433741 28 T>N No EVA
rs3389422310 153 R>K No EVA
rs3389371956 272 D>E No EVA
rs3412991836 310 E>D No EVA
rs3389371895 437 L>V No EVA
rs265655380 500 D>E No EVA
rs3389403235 502 P>S No EVA
rs3389426265 503 G>D No EVA
rs259759688 509 S>P No EVA
rs3389413856 537 A>T No EVA
rs3389433730 579 E>V No EVA
rs239556814 706 T>A No EVA
rs255378838 706 T>M No EVA
rs3389430167 825 L>F No EVA
rs3389424410 849 A>T No EVA
rs3389415922 863 E>K No EVA
rs3389381934 964 P>H No EVA
rs3389371891 981 A>V No EVA
rs3389371969 986 R>K No EVA
rs3389403226 1000 N>S No EVA
rs3389426264 1033 A>P No EVA
rs3389371887 1035 E>* No EVA
rs3407151063 1039 R>L No EVA

No associated diseases with P57080

13 regional properties for P57080

Type Name Position InterPro Accession
domain C2 domain 158 - 277 IPR000008
domain Protein kinase domain 342 - 600 IPR000719
domain AGC-kinase, C-terminal 601 - 671 IPR000961
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 36 - 87 IPR002219-1
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 101 - 153 IPR002219-2
active_site Serine/threonine-protein kinase, active site 462 - 474 IPR008271
binding_site Protein kinase, ATP binding site 348 - 371 IPR017441
domain Protein kinase, C-terminal 623 - 662 IPR017892
domain Diacylglycerol/phorbol-ester binding 34 - 48 IPR020454-1
domain Diacylglycerol/phorbol-ester binding 50 - 59 IPR020454-2
domain Diacylglycerol/phorbol-ester binding 63 - 74 IPR020454-3
domain Diacylglycerol/phorbol-ester binding 140 - 152 IPR020454-4
domain Classical protein kinase C beta, catalytic domain 341 - 664 IPR034664

Functions

Description
EC Number 3.4.19.12 Omega peptidases
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • The longer muscle-specific isoform (USP25m) Some transient punctuate nuclear location in myotubes during myocyte development
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
proteasome complex A large multisubunit complex which catalyzes protein degradation, found in eukaryotes, archaea and some bacteria. In eukaryotes, this complex consists of the barrel shaped proteasome core complex and one or two associated proteins or complexes that act in regulating entry into or exit from the core.

2 GO annotations of molecular function

Name Definition
cysteine-type deubiquitinase activity An thiol-dependent isopeptidase activity that cleaves ubiquitin from a target protein to which it is conjugated.
SUMO binding Binding to the small ubiquitin-like protein SUMO.

7 GO annotations of biological process

Name Definition
immune response Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat.
interleukin-17-mediated signaling pathway The series of molecular signals initiated by interleukin-17 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
mRNA metabolic process The chemical reactions and pathways involving mRNA, messenger RNA, which is responsible for carrying the coded genetic 'message', transcribed from DNA, to sites of protein assembly at the ribosomes.
regulation of protein stability Any process that affects the structure and integrity of a protein, altering the likelihood of its degradation or aggregation.
response to oxidative stress Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
stress-activated protein kinase signaling cascade The series of molecular signals in which a stress-activated protein kinase (SAPK) cascade relays a signal.
ubiquitin-dependent protein catabolic process The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein.

4 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q93009 USP7 Ubiquitin carboxyl-terminal hydrolase 7 Homo sapiens (Human) PR
Q9UHP3 USP25 Ubiquitin carboxyl-terminal hydrolase 25 Homo sapiens (Human) EV
Q6A4J8 Usp7 Ubiquitin carboxyl-terminal hydrolase 7 Mus musculus (Mouse) PR
P56399 Usp5 Ubiquitin carboxyl-terminal hydrolase 5 Mus musculus (Mouse) PR
10 20 30 40 50 60
MTVEQNVLQQ SAAQKHQQTF LNQLREITGI NDAQILQQAL KDSNGNLELA VAFLTAKNAK
70 80 90 100 110 120
TPPQEETGYY QTALPGNDRY ISVGSQADAN VIDLTGDDKD DLQRAIALSL AESNRAFRET
130 140 150 160 170 180
GITDEEQAIS RVLEASIAEN KACLKRTPIE VWRDSRNPYD RKRQEKAPVG LKNVGNTCWF
190 200 210 220 230 240
SAVIQSLFNL LEFRRLVLNY KPPSNAQDLP RNQKEHRNLP FMRELRYLFA LLVGTKRKYV
250 260 270 280 290 300
DPSRAVEILK DAFKSNDSQQ QDVSEFTHKL LDWLEDAFQM KAEEETDEEK PKNPMVELFY
310 320 330 340 350 360
GRFLAMGVLE GKKFENTEMF GQYPLQVNGF KDLHECLEAA MIEGEIESLH SDNSGKSGQE
370 380 390 400 410 420
HWFTELPPVL TFELSRFEFN QALGRPEKIH NKLEFPQVLY LDRYMHRNRE ITRIKREEIK
430 440 450 460 470 480
RLKDYLTVLQ QRLERYLSYG SGPKRFPLVD VLQYALEFAS SKPVCTSPVD DIDASSSASG
490 500 510 520 530 540
PLPSQSLPST TEQQGPCASD LPGSSSPASG AALPLRSVIH KPFTQSRIPP DLPMHPAPRH
550 560 570 580 590 600
ITEEELCVLE SCLHRWRTEI ENDTRDLQES ISRIHRTIEL MYSDKSMIQV PYRLHAVLVH
610 620 630 640 650 660
EGQANAGHYW AYIFDHRESR WMKYNDIAVT KSSWEELVRD SFGGYRNASA YCLMYIDDKA
670 680 690 700 710 720
QFLIQEEFNK ETGQALVGME TLPPDLRDFV EEDNQRFEKE LEEWDTQLAQ RSLQEKLLAA
730 740 750 760 770 780
PKLREAEASA TTAQAGGADY LEQPSRSDLS KHWKEETLRV IAKASHDLED KGPETVLQSA
790 800 810 820 830 840
IKLEYSRLVK LAQEDTPPET DYRLHHVLVY FIQNQAPKKI IEKTLLEQFG DRNLSFDERC
850 860 870 880 890 900
HNIMKVAQAK LEMIKPEEVN LEEYEEWHAD YKKFRETTMY LITGLENFQR ESYIDSLLFL
910 920 930 940 950 960
LCAYQNNKEL LSKGPYRGHD GELISHYRRE CLLKLNEQAA ELFESGEDGD VNNGLIIMNE
970 980 990 1000 1010 1020
FIVPFLPLLL VDDMEEKDIL AVEDMRNRWC SYLGQEMEAN LQEKLTDFLP KLLDCSTEIK
1030 1040 1050
GFHEPPKLPS YSAHELCERF ARIMLSLSRT PADGR