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Protein

E3 ubiquitin-protein ligase TRIP12

Gene

Trip12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardeless of the presence of lysine residues in target proteins. In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes.By similarity

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1992Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase TRIP12 (EC:2.3.2.26)
Alternative name(s):
HECT-type E3 ubiquitin transferase TRIP12
Thyroid receptor-interacting protein 12
Short name:
TR-interacting protein 12
Short name:
TRIP-12
Gene namesi
Name:Trip12
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:1309481 Trip12

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryonic lethality in the middle stage of development. Embryos exhibit growth arrest, while ES cells are viable. ES cells show decreased proliferation, but maintain both the undifferentiated state and the ability to differentiate.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00004196892 – 2025E3 ubiquitin-protein ligase TRIP12Add BLAST2024

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineBy similarity1
Modified residuei12PhosphoserineBy similarity1
Modified residuei77PhosphoserineBy similarity1
Modified residuei85PhosphoserineCombined sources1
Modified residuei100PhosphoserineBy similarity1
Modified residuei181N6-acetyllysineCombined sources1
Modified residuei310PhosphoserineCombined sources1
Modified residuei312PhosphoserineCombined sources1
Modified residuei975PhosphoserineCombined sources1
Modified residuei1024PhosphoserineCombined sources1
Modified residuei1030PhosphoserineCombined sources1
Modified residuei1049PhosphoserineBy similarity1
Modified residuei1063PhosphoserineBy similarity1
Modified residuei1350PhosphoserineCombined sources1
Modified residuei1355PhosphoserineCombined sources1
Modified residuei1362PhosphoserineCombined sources1
Modified residuei1409PhosphoserineBy similarity1
Modified residuei1410PhosphothreonineBy similarity1
Modified residuei1458N6-acetyllysineCombined sources1
Modified residuei1460PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiG5E870
MaxQBiG5E870
PaxDbiG5E870
PeptideAtlasiG5E870
PRIDEiG5E870

PTM databases

iPTMnetiG5E870
PhosphoSitePlusiG5E870
SwissPalmiG5E870

Expressioni

Gene expression databases

BgeeiENSMUSG00000026219 Expressed in 299 organ(s), highest expression level in secondary oocyte
ExpressionAtlasiG5E870 baseline and differential
GenevisibleiG5E870 MM

Interactioni

Subunit structurei

Interacts with MYC; leading to disrupt interaction with isoform p19ARF/ARF of CDKN2A. Interacts with TRADD; leading to disrupt interaction with isoform p19ARF/ARF of CDKN2A. Interacts with SMARCC1; leading to disrupt interaction with SMARCE1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200117, 5 interactors
IntActiG5E870, 3 interactors
MINTiG5E870
STRINGi10090.ENSMUSP00000027421

Structurei

3D structure databases

SMRiG5E870
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini755 – 869WWEPROSITE-ProRule annotationAdd BLAST115
Domaini1918 – 2025HECTPROSITE-ProRule annotationAdd BLAST108

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1529 – 1603K-boxBy similarityAdd BLAST75

Sequence similaritiesi

Belongs to the UPL family. K-HECT subfamily.Curated

Phylogenomic databases

eggNOGiKOG0168 Eukaryota
KOG0170 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00530000063470
HOGENOMiHOG000007873
HOVERGENiHBG062085
InParanoidiG5E870
KOiK10590
OMAiHFEVITV
OrthoDBiEOG091G00GQ
TreeFamiTF323674

Family and domain databases

CDDicd00078 HECTc, 1 hit
Gene3Di1.25.10.10, 1 hit
3.30.720.50, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR004170 WWE-dom
IPR018123 WWE-dom_subgr
IPR037197 WWE_dom_sf
PfamiView protein in Pfam
PF00632 HECT, 1 hit
PF02825 WWE, 1 hit
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SM00678 WWE, 1 hit
SUPFAMiSSF117839 SSF117839, 1 hit
SSF48371 SSF48371, 2 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit
PS50918 WWE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 10 potential isoforms that are computationally mapped.Show allAlign All

G5E870-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSNRPNNNPG GSLRRSQRNT AGAQPQDDSI GGRSCSSSSA VIVPQPEDPD
60 70 80 90 100
RANTSERQKT GQVPKKDNSR GVKRSASPDY NRTNSPSSAK KPRAFQHIES
110 120 130 140 150
FSETNKPHSK SKKRHLDQEQ QLKSAQLPST SKAHTRKSVA AGSSRNQKRK
160 170 180 190 200
RTESSCVKSG SGSESTGAEE RSAKPIKLAS KSATSAKAGC STITDSSSAA
210 220 230 240 250
STSSSSSAIA SASSTVPAGA RVKQGKDQNK ARRSRSASSP SPRRSSREKE
260 270 280 290 300
QSKTGGSSKF DWAARFSPKV SLPKTKLSLP GSSKSETSKP GPSGLQAKLA
310 320 330 340 350
SLRKSTKKRS ESPPAELPSL RRSTRQKTTG SCASTSRRGS GLGKRGAAEA
360 370 380 390 400
RRQEKMADPE SNQETVNSSA ARTDEAPQGA AASSSVAGAV GMTTSGESES
410 420 430 440 450
DDSEMGRLQA LLEARGLPPH LFGPLGPRMS QLFHRTIGSG ASSKAQQLLQ
460 470 480 490 500
GLQASDESQQ LQAVIEMCQL LVMGNEETLG GFPVKSVVPA LITLLQMEHN
510 520 530 540 550
FDIMNHACRA LTYMMEALPR SSAVVVDAIP VFLEKLQVIQ CIDVAEQALT
560 570 580 590 600
ALEMLSRRHS KAILQAGGLA DCLLYLEFFS INAQRNALAI AANCCQSITP
610 620 630 640 650
DEFHFVADSL PLLTQRLTHQ DKKSVESTCL CFARLVDNFQ HEENLLQQVA
660 670 680 690 700
SKDLLTNVQQ LLVVTPPILS SGMFIMVVRM FSLMCSNCPT LAVQLMKQNI
710 720 730 740 750
AETLHFLLCG ASNGSCQEQI DLVPRSPQEL YELTSLICEL MPCLPKEGIF
760 770 780 790 800
AVDTMLKKGN AQNTDGAIWQ WRDDRGLWHP YNRIDSRIIE AAHQVGEDEI
810 820 830 840 850
SLSTLGRVYT IDFNSMQQIN EDTGTARAIQ RKPNPLANSN TSGYSELKKD
860 870 880 890 900
DARAQLMKED PELAKSFIKT LFGVLYEVYS SSAGPAVRHK CLRAILRIIY
910 920 930 940 950
FADAELLKDV LKNHAVSSHI ASMLSSQDLK IVVGALQMAE ILMQKLPDIF
960 970 980 990 1000
SVYFRREGVM HQVKHLAESE SLLTSPPKAC TNGSGSLGST TPASSGTATA
1010 1020 1030 1040 1050
ATNASADLGS PSLQHSRDDS LDLSPQGRLS DVLKRKRLPK RGPRRPKYSP
1060 1070 1080 1090 1100
PRDDDKVDNQ AKSPTTTQSP KSSFLASLNP KTWGRLSAQS NSNNIEPART
1110 1120 1130 1140 1150
AGVSGLARAA SKDTISNNRE KIKGWIKEQA HKFVERYFSS ENMDGSNPAL
1160 1170 1180 1190 1200
NVLQRLCAAT EQLNLQVDGG AECLVEIRSI VSESDVSSFE IQHSGFVKQL
1210 1220 1230 1240 1250
LLYLTSKNEK DAVGREIRLK RFLHVFFSSP LPGEEPVGRV EPVGHAPLLA
1260 1270 1280 1290 1300
LVHKMNNCLS QMEQFPVKVH DFPSGNGAGG SFSLNRGSQA LKFFNTHQLK
1310 1320 1330 1340 1350
CQLQRHPDCA NVKQWKGGPV KIDPLALVQA IERYLVVRGY GRVREDDEDS
1360 1370 1380 1390 1400
DDDGSDEEID ESLAAQFLNS GNVRHRLQFY IGEHLLPYNM TVYQAVRQFS
1410 1420 1430 1440 1450
VQAEDEREST DDESNPLGRA GIWTKTHTIW YKPVREDEES TKDCVGGKRG
1460 1470 1480 1490 1500
RAQTAPTKTS PRNAKKHDEL WHDGVCPSVA NPLEVYLIPT PPENITFEDP
1510 1520 1530 1540 1550
SLDVILLLRV LHAISRYWYY LYDNAMCKEI IPTSEFINSK LTAKANRQLQ
1560 1570 1580 1590 1600
DPLVIMTGNI PTWLTELGKT CPFFFPFDTR QMLFYVTAFD RDRAMQRLLD
1610 1620 1630 1640 1650
TNPEINQSDS QDSRVAPRLD RKKRTVNREE LLKQAESVMQ DLGSSRAMLE
1660 1670 1680 1690 1700
IQYENEVGTG LGPTLEFYAL VSQELQRADL CLWRGEEVTL SNPKGSQEGT
1710 1720 1730 1740 1750
KYIQNLQGLF ALPFGRTAKP AHIAKVKMKF RFLGKLMAKA IMDFRLVDLP
1760 1770 1780 1790 1800
LGLPFYKWML RQETSLTSHD LFDIDPVVAR SVYHLEDIVR QKKRLEQDKS
1810 1820 1830 1840 1850
QTKESLQYAL ETLTMNGCSV EDLGLDFTLP GFPNIELKKG GKDIPVTIHN
1860 1870 1880 1890 1900
LEEYLRLVIF WALNEGVCRQ FDSFRDGFES VFPLCHLQYF YPEELDQLLC
1910 1920 1930 1940 1950
GSKADTWDAK TLMECCRPDH GYTHDSRAVK FLFEILSSFD NEQQRLFLQF
1960 1970 1980 1990 2000
VTGSPRLPVG GFRSLNPPLT IVRKTFESTE NPDDFLPSVM TCVNYLKLPD
2010 2020
YSSIDIMRDK LLIAAREGQQ SFHLS
Length:2,025
Mass (Da):224,128
Last modified:December 14, 2011 - v1
Checksum:i25A71E35838DF64C
GO

Computationally mapped potential isoform sequencesi

There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WNZ7A0A087WNZ7_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
1,992Annotation score:
A0A087WRV6A0A087WRV6_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
830Annotation score:
A0A0B4J1N9A0A0B4J1N9_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
982Annotation score:
A0A087WSG4A0A087WSG4_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
213Annotation score:
Q3TP48Q3TP48_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
146Annotation score:
A0A087WP92A0A087WP92_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
423Annotation score:
A0A087WRK9A0A087WRK9_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
33Annotation score:
A0A087WS33A0A087WS33_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
98Annotation score:
A0A087WS65A0A087WS65_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
65Annotation score:
A0A087WQ02A0A087WQ02_MOUSE
E3 ubiquitin-protein ligase TRIP12
Trip12
346Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC123882 Genomic DNA No translation available.
CH466629 Genomic DNA Translation: EDL02171.1
CH466629 Genomic DNA Translation: EDL02178.1
CH466629 Genomic DNA Translation: EDL02182.1
AK034814 mRNA Translation: BAC28839.1
AK134397 mRNA Translation: BAE22126.1
AK158807 mRNA Translation: BAE34675.1
BC034113 mRNA Translation: AAH34113.2
CCDSiCCDS35633.1
RefSeqiNP_598736.4, NM_133975.4
UniGeneiMm.209265

Genome annotation databases

EnsembliENSMUST00000027421; ENSMUSP00000027421; ENSMUSG00000026219
ENSMUST00000186465; ENSMUSP00000140224; ENSMUSG00000026219
GeneIDi14897
KEGGimmu:14897
UCSCiuc007bsy.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC123882 Genomic DNA No translation available.
CH466629 Genomic DNA Translation: EDL02171.1
CH466629 Genomic DNA Translation: EDL02178.1
CH466629 Genomic DNA Translation: EDL02182.1
AK034814 mRNA Translation: BAC28839.1
AK134397 mRNA Translation: BAE22126.1
AK158807 mRNA Translation: BAE34675.1
BC034113 mRNA Translation: AAH34113.2
CCDSiCCDS35633.1
RefSeqiNP_598736.4, NM_133975.4
UniGeneiMm.209265

3D structure databases

SMRiG5E870
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200117, 5 interactors
IntActiG5E870, 3 interactors
MINTiG5E870
STRINGi10090.ENSMUSP00000027421

PTM databases

iPTMnetiG5E870
PhosphoSitePlusiG5E870
SwissPalmiG5E870

Proteomic databases

EPDiG5E870
MaxQBiG5E870
PaxDbiG5E870
PeptideAtlasiG5E870
PRIDEiG5E870

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000027421; ENSMUSP00000027421; ENSMUSG00000026219
ENSMUST00000186465; ENSMUSP00000140224; ENSMUSG00000026219
GeneIDi14897
KEGGimmu:14897
UCSCiuc007bsy.1 mouse

Organism-specific databases

CTDi9320
MGIiMGI:1309481 Trip12

Phylogenomic databases

eggNOGiKOG0168 Eukaryota
KOG0170 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00530000063470
HOGENOMiHOG000007873
HOVERGENiHBG062085
InParanoidiG5E870
KOiK10590
OMAiHFEVITV
OrthoDBiEOG091G00GQ
TreeFamiTF323674

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

ChiTaRSiTrip12 mouse
PROiPR:G5E870
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026219 Expressed in 299 organ(s), highest expression level in secondary oocyte
ExpressionAtlasiG5E870 baseline and differential
GenevisibleiG5E870 MM

Family and domain databases

CDDicd00078 HECTc, 1 hit
Gene3Di1.25.10.10, 1 hit
3.30.720.50, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR004170 WWE-dom
IPR018123 WWE-dom_subgr
IPR037197 WWE_dom_sf
PfamiView protein in Pfam
PF00632 HECT, 1 hit
PF02825 WWE, 1 hit
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SM00678 WWE, 1 hit
SUPFAMiSSF117839 SSF117839, 1 hit
SSF48371 SSF48371, 2 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit
PS50918 WWE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTRIPC_MOUSE
AccessioniPrimary (citable) accession number: G5E870
Secondary accession number(s): Q3TY88
, Q3UYT5, Q8BM59, Q8K051
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2012
Last sequence update: December 14, 2011
Last modified: October 10, 2018
This is version 64 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
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