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Basic Information Integrated Annotations
Tag Content
iUUCD ID IUUC-Hsa-046147
UUCD1 version UUC-HoS-00123
Ensembl Protein ID ENSP00000283943.4
UniProt Accession Q14669; D4HL82; Q14CA3; Q14CF1; Q15644; Q53R87; Q53TE7; TRIPC_HUMAN
Genbank Protein ID ACC99349.1; BAA05837.2; AAY14755.1; AAY14681.1; AAI14557.1; AAI13892.1; AAC41731.1
Protein Name E3 ubiquitin-protein ligase TRIP12; E3 ubiquitin-protein ligase for Arf; HECT-type E3 ubiquitin transferase TRIP12; Thyroid receptor-interacting protein 12
Genbank Nucleotide ID EU489742; D28476; AC009973; AC093384; AC105380; BC113891; L40383
Gene Name TRIP12; KIAA0045; ULF
Ensembl Information
Ensembl Gene ID Ensembl Transcript ID Ensembl Protein ID
ENSG00000153827.13 ENST00000283943.9 ENSP00000283943.4
ENSG00000153827.13 ENST00000389045.7 ENSP00000373697.3
ENSG00000153827.13 ENST00000389044.8 ENSP00000373696.4
ENSG00000153827.13 ENST00000418123.1 ENSP00000408330.1
ENSG00000153827.13 ENST00000409677.5 ENSP00000386388.1
ENSG00000153827.13 ENST00000453485.1 ENSP00000400967.1
Annotation
Cancer Mutation
TCGAICGCCOSMICCGAP
IntOGen
Single Nucleotide Polymorphisms (SNP)
dbSNP
mRNA Expression
GEOArrayExpressTCGAICGC
COSMICTHPAHPM
DNA & RNA Element
UTRdbAREsitecircBasecircRNADb
CircNetmiRTarBasemicroRNATRANSFAC
miRWalkTargetScanRepTarmiRNAMap
SomamiRmiRcodeRAID2
Protein-protein Interaction
IIDiRefIndexPINAHINT
MenthaInWeb_IM
Disease-associated Information
ClinVarGWASdbGWAS CentralOMIM
Drug and target
TTD
Post-translational Modifications (PTMs)
CPLMdbPAFPhosphositePlusdbPTM
HPRDPhospho.ELMUniProtPHOSIDA
BioGRIDmUbiSiDa
DNA Methylation
TCGAICGCCOSMIC
Protein Expression/Proteomics
THPAHPMGPMDB
Status Reviewed
Details
Family Domain References (PMIDs)
E3 activity/HECT HECT 20208519; 20829358; 20175895; 18627766
Classification
Family E-value Score Start End
E3 activity/HECT 3.60e-96 324.1 1613 1992
Active Site
Position(s) Description Evidence
1959 Glycyl thioester intermediate {ECO:0000305}
Domain Profile

   E3 activity/HECT
   S: 6    kkrlevefvgEegldlgGvtreflallskelqnpdlglflysendketlq..pnpdsglknp.....................ehlklFe 72
           ++ le+++++E g++l G+t+ef+al+s+elq++dlgl++ +e   ++ +   + +++                         ++   F+
   Q: 1613 RAMLEIQYENEVGTGL-GPTLEFYALVSQELQRADLGLWRGEEVTLSNPKgsQEGTKY---IqnlqglfalpfgrtakpahiaKVKMKFR 1698
           56899***********.**********************6665533332200222333...14458888999**********9999**** PP
   S: 73   flGrllgkalqdgrlldlplsksfyklllgkklsl..edleevdpelykslkeikena......es.....................die 133
           flG+l++ka++d rl+dlpl  +fyk +l+++ sl  +dl ++dp +++s+  +++ +      e+                     ++e
   Q: 1699 FLGKLMAKAIMDFRLVDLPLGLPFYKWMLRQETSLtsHDLFDIDPVVARSVYHLEDIVrqkkrlEQdksqtkeslqyaletltmngcSVE 1788
           *******************************654444**************999999855555511555666666554444444444444 PP
   S: 134  elgldltfsvseei.....lgetkeeeLkpgGenipVtneNkeeYvklvveyrlkegikeqveafreGfneviplellslFteeelelli 218
           +            +     l+   + eLk gG++ipVt+ N+eeY +lv+ + l+eg+ +q+++fr+Gf++v+pl++l++F +eel++l+
   Q: 1789 D------------LgldftLPGFPNIELKKGGKDIPVTIHNLEEYLRLVIFWALNEGVSRQFDSFRDGFESVFPLSHLQYFYPEELDQLL 1866
           4............25555578999****************************************************************** PP
   S: 219  cGe..eeidvedlkketkykggytedspaiqwFwevleefsseerkafLqFvTgssrlPlgGfaelkprlfvirk.....dasddrlPss 301
           cG+  +++d+++l + ++ ++gyt+ds+a+++++e+l++f++e+++ fLqFvTgs+rlP+gGf++l+p l+++rk     ++ dd lPs+
   Q: 1867 CGSkaDTWDAKTLMECCRPDHGYTHDSRAVKFLFEILSSFDNEQQRLFLQFVTGSPRLPVGGFRSLNPPLTIVRKtfestENPDDFLPSV 1956
           ***7778999999999999***********************************************************988888****** PP
   S: 302  nTCfnyLkLPeYsskeilkekLlyAieet.kgFels 336
           +TC+nyLkLP+Yss ei++ekLl+A +e+ ++F+ls
   Q: 1957 MTCVNYLKLPDYSSIEIMREKLLIAAREGqQSFHLS 1992
           *********************************985 PP
   
Organism Homo sapiens
Functional Description
(View)

Functional Description


     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.
 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.
Protein Sequence
(Fasta)
MSNRPNNNPG GSLRRSQRNT AGAQPQDDSI GGRSCSSSSA VIVPQPEDPD RANTSERQKT 60
GQVPKKDNSR GVKRSASPDY NRTNSPSSAK KPKALQHTES PSETNKPHSK SKKRHLDQEQ 120
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Protein Fasta Sequence


>IUUC-Hsa-046147|E3,HECT|Homo sapiens
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Nucleotide Sequence
(Fasta)
GTCATTATGG GTGGGGCTGA AGCGCAGAGC AGCTGAAACA TTTTTATACC ACCACCCGCA 60
CACTTTCAAT GGGATAGAAG GGACTCCAAA AGGTAAGAGC TCCCAATCGT CAGTTGCTAC 120
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Nucleotide Fasta Sequence


>IUUC-Hsa-046147|E3,HECT|Homo sapiens
Please wait for a moment...
Sequence Source Ensembl
Keyword

KW-0007--Acetylation
KW-0025--Alternative splicing
KW-0181--Complete proteome
KW-0227--DNA damage
KW-0234--DNA repair
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-1185--Reference proteome
KW-0808--Transferase
KW-0833--Ubl conjugation pathway
Interpro

IPR011989--ARM-like
IPR016024--ARM-type_fold
IPR000569--HECT_dom
IPR004170--WWE-dom
PROSITE

PS50237--HECT
PS50918--WWE
Pfam

PF00632--HECT
SMART

SM00119--HECTc
Gene Ontology

GO:0005829--C:cytosol
GO:0016607--C:nuclear speck
GO:0005654--C:nucleoplasm
GO:0005634--C:nucleus
GO:0046966--F:thyroid hormone receptor binding
GO:0004842--F:ubiquitin-protein transferase activity
GO:0006974--P:cellular response to DNA damage stimulus
GO:0006281--P:DNA repair
GO:0009790--P:embryo development
GO:2000780--P:negative regulation of double-strand break repair
GO:1901315--P:negative regulation of histone H2A K63-linked ubiquitination
GO:0000209--P:protein polyubiquitination
GO:0042787--P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process
KEGG hsa:9320
Orthology
iUUCD ID Species Identity E-value Score
IUUC-Ata-000750 Aegilops tauschii 38.69 2.00e-126 447.00
IUUC-Aml-001502 Ailuropoda melanoleuca 95.83 0.00e+00 3625.00
IUUC-Atr-002821 Amborella trichopoda 37.45 7.00e-117 416.00
IUUC-Apl-003531 Anas platyrhynchos 91.04 0.00e+00 3359.00
IUUC-Aly-005962 Arabidopsis lyrata 38.94 8.00e-115 409.00
IUUC-Ath-006636 Arabidopsis thaliana 38.66 5.00e-114 406.00
IUUC-Ago-007875 Ashbya gossypii 36.20 1.00e-81 299.00
IUUC-Acl-008242 Aspergillus clavatus 35.70 2.00e-113 404.00
IUUC-Afl-008736 Aspergillus flavus 38.83 2.00e-110 395.00
IUUC-Afu-008812 Aspergillus fumigatus 35.10 5.00e-114 406.00
IUUC-Ani-009407 Aspergillus nidulans 36.82 3.00e-110 394.00
IUUC-Ang-009763 Aspergillus niger 40.00 4.00e-106 380.00
IUUC-Aor-009941 Aspergillus oryzae 30.77 1.00e-112 401.00
IUUC-Ate-010459 Aspergillus terreus 36.42 1.00e-85 312.00
IUUC-Ame-011761 Astyanax mexicanus 85.37 0.00e+00 2919.00
IUUC-Bgr-012265 Blumeria graminis 34.86 4.00e-104 374.00
IUUC-Bta-013070 Bos taurus 98.34 0.00e+00 3647.00
IUUC-Bci-013890 Botrytis cinerea 39.72 2.00e-102 368.00
IUUC-Bdi-014046 Brachypodium distachyon 38.47 6.00e-122 433.00
IUUC-Bol-015942 Brassica oleracea 44.23 1.00e-114 408.00
IUUC-Bra-016849 Brassica rapa 44.23 4.00e-114 407.00
IUUC-Cja-019046 Callithrix jacchus 96.43 0.00e+00 3600.00
IUUC-Cfa-020521 Canis familiaris 94.95 0.00e+00 3486.00
IUUC-Cpo-021639 Cavia porcellus 91.63 0.00e+00 3501.00
IUUC-Cre-022767 Chlamydomonas reinhardtii 39.88 1.00e-89 323.00
IUUC-Csa-023231 Chlorocebus sabaeus 95.36 0.00e+00 3596.00
IUUC-Cho-024380 Choloepus hoffmanni 88.73 0.00e+00 3264.00
IUUC-Cin-025482 Ciona intestinalis 51.21 7.00e-160 557.00
IUUC-Csv-026121 Ciona savignyi 49.47 0.00e+00 1562.00
IUUC-Cgl-026716 Colletotrichum gloeosporioides 34.98 1.00e-110 395.00
IUUC-Cne-026857 Cryptococcus neoformans 39.89 2.00e-94 342.00
IUUC-Cme-027226 Cyanidioschyzon merolae 35.14 4.00e-74 274.00
IUUC-Dre-028174 Danio rerio 85.28 0.00e+00 2967.00
IUUC-Dor-030939 Dipodomys ordii 88.27 0.00e+00 2789.00
IUUC-Dse-031444 Dothistroma septosporum 39.31 2.00e-105 378.00
IUUC-Dme-032162 Drosophila melanogaster 63.41 5.00e-158 553.00
IUUC-Ete-032345 Echinops telfairi 92.38 0.00e+00 2308.00
IUUC-Eca-033229 Equus caballus 95.25 0.00e+00 3537.00
IUUC-Eeu-035205 Erinaceus europaeus 88.76 0.00e+00 3152.00
IUUC-Fca-036444 Felis catus 95.05 0.00e+00 3569.00
IUUC-Fal-037131 Ficedula albicollis 90.28 0.00e+00 3402.00
IUUC-Fox-038035 Fusarium oxysporum 38.54 4.00e-110 392.00
IUUC-Fso-038320 Fusarium solani 36.91 6.00e-110 393.00
IUUC-Gmo-039497 Gadus morhua 82.75 0.00e+00 3109.00
IUUC-Ggr-040057 Gaeumannomyces graminis 34.90 3.00e-108 387.00
IUUC-Gga-041021 Gallus gallus 90.28 0.00e+00 3408.00
IUUC-Gac-042474 Gasterosteus aculeatus 84.18 0.00e+00 3090.00
IUUC-Gma-043060 Glycine max 38.92 4.00e-122 433.00
IUUC-Ggo-044855 Gorilla gorilla 96.67 0.00e+00 3609.00
IUUC-Hvu-047775 Hordeum vulgare 38.69 7.00e-125 442.00
IUUC-Itr-048131 Ictidomys tridecemlineatus 96.35 0.00e+00 3499.00
IUUC-Kpa-049098 Komagataella pastoris 38.10 4.00e-86 313.00
IUUC-Lch-049818 Latimeria chalumnae 84.29 0.00e+00 3070.00
IUUC-Lpe-051017 Leersia perrieri 38.44 2.00e-118 421.00
IUUC-Loc-051777 Lepisosteus oculatus 84.68 0.00e+00 3279.00
IUUC-Lma-052990 Leptosphaeria maculans 39.74 6.00e-112 400.00
IUUC-Laf-053727 Loxodonta africana 95.44 0.00e+00 3578.00
IUUC-Mcc-055799 Macaca mulatta 93.90 0.00e+00 3505.00
IUUC-Meu-056065 Macropus eugenii 93.88 0.00e+00 2103.00
IUUC-Mor-057054 Magnaporthe oryzae 38.86 2.00e-107 384.00
IUUC-Mpo-057417 Magnaporthe poae 39.55 1.00e-109 392.00
IUUC-Mtr-057849 Medicago truncatula 37.36 1.00e-113 405.00
IUUC-Mla-058870 Melampsora laricipopulina 42.57 7.00e-107 382.00
IUUC-Mga-059580 Meleagris gallopavo 90.92 0.00e+00 2956.00
IUUC-Mvi-060507 Microbotryum violaceum 40.19 9.00e-113 402.00
IUUC-Mmr-060816 Microcebus murinus 94.54 0.00e+00 3565.00
IUUC-Mdo-062866 Monodelphis domestica 90.62 0.00e+00 3273.00
IUUC-Mmu-063906 Mus musculus 95.75 0.00e+00 3563.00
IUUC-Mac-064675 Musa acuminata 38.92 2.00e-111 396.00
IUUC-Mpu-066199 Mustela putorius furo 92.79 0.00e+00 3461.00
IUUC-Mlu-067110 Myotis lucifugus 95.90 0.00e+00 3558.00
IUUC-Nfi-068482 Neosartorya fischeri 35.25 6.00e-114 406.00
IUUC-Ncr-068906 Neurospora crassa 39.13 3.00e-109 391.00
IUUC-Nle-069410 Nomascus leucogenys 96.32 0.00e+00 3594.00
IUUC-Opr-070401 Ochotona princeps 86.29 0.00e+00 3018.00
IUUC-Ont-072100 Oreochromis niloticus 79.92 0.00e+00 3046.00
IUUC-Oan-073121 Ornithorhynchus anatinus 90.72 0.00e+00 3530.00
IUUC-Ocu-074623 Oryctolagus cuniculus 92.79 0.00e+00 3494.00
IUUC-Oba-075380 Oryza barthii 36.51 2.00e-113 404.00
IUUC-Obr-076915 Oryza brachyantha 37.77 7.00e-119 422.00
IUUC-Ogl-077055 Oryza glaberrima 38.70 3.00e-118 421.00
IUUC-Ogu-078892 Oryza glumaepatula 40.95 1.00e-112 401.00
IUUC-Oin-079256 Oryza indica 38.52 5.00e-117 416.00
IUUC-Olo-080343 Oryza longistaminata 38.52 2.00e-117 418.00
IUUC-Ome-081422 Oryza meridionalis 38.24 5.00e-117 416.00
IUUC-Oni-083047 Oryza nivara 41.13 1.00e-114 408.00
IUUC-Opu-083641 Oryza punctata 36.44 4.00e-111 396.00
IUUC-Oru-084439 Oryza rufipogon 40.95 3.00e-113 403.00
IUUC-Osa-085972 Oryza sativa 38.44 2.00e-116 413.00
IUUC-Ola-087173 Oryzias latipes 80.43 0.00e+00 3029.00
IUUC-Olu-087871 Ostreococcus lucimarinus 36.89 8.00e-89 321.00
IUUC-Oga-087908 Otolemur garnettii 95.55 0.00e+00 3579.00
IUUC-Oar-090277 Ovis aries 95.06 0.00e+00 3604.00
IUUC-Ptr-091543 Pan troglodytes 99.90 0.00e+00 3645.00
IUUC-Pan-092243 Papio anubis 93.86 0.00e+00 3502.00
IUUC-Psi-093150 Pelodiscus sinensis 92.36 0.00e+00 3526.00
IUUC-Pno-094891 Phaeosphaeria nodorum 40.94 4.00e-113 404.00
IUUC-Ppa-095181 Physcomitrella patens 42.14 2.00e-107 383.00
IUUC-Pfo-096267 Poecilia formosa 79.35 0.00e+00 3021.00
IUUC-Pab-098072 Pongo abelii 96.62 0.00e+00 3606.00
IUUC-Pop-099190 Populus trichocarpa 41.34 4.00e-116 414.00
IUUC-Pca-100311 Procavia capensis 90.83 0.00e+00 3296.00
IUUC-Ppe-101284 Prunus persica 37.52 3.00e-116 414.00
IUUC-Pva-102215 Pteropus vampyrus 90.29 0.00e+00 1298.00
IUUC-Pgr-103694 Puccinia graminis 40.68 3.00e-104 374.00
IUUC-Ptt-103916 Puccinia triticina 39.00 2.00e-98 355.00
IUUC-Pte-104346 Pyrenophora teres 39.59 3.00e-110 394.00
IUUC-Pyt-104508 Pyrenophora triticirepentis 39.66 2.00e-110 394.00
IUUC-Rno-105315 Rattus norvegicus 92.55 0.00e+00 3422.00
IUUC-Sce-106273 Saccharomyces cerevisiae 35.00 6.00e-71 263.00
IUUC-Sha-106835 Sarcophilus harrisii 92.31 0.00e+00 3557.00
IUUC-Sja-107943 Schizosaccharomyces japonicus 37.58 1.00e-94 342.00
IUUC-Spo-108081 Schizosaccharomyces pombe 38.54 2.00e-94 342.00
IUUC-Ssl-108560 Sclerotinia sclerotiorum 39.92 4.00e-106 380.00
IUUC-Smo-109590 Selaginella moellendorffii 43.28 4.00e-112 400.00
IUUC-Sit-110717 Setaria italica 37.94 5.00e-120 426.00
IUUC-Sly-111469 Solanum lycopersicum 39.08 1.00e-121 432.00
IUUC-Stu-112896 Solanum tuberosum 38.22 1.00e-105 377.00
IUUC-Sar-113224 Sorex araneus 92.70 0.00e+00 1952.00
IUUC-Sbi-114313 Sorghum bicolor 38.02 1.00e-123 438.00
IUUC-Sre-114993 Sporisorium reilianum 34.09 2.00e-100 362.00
IUUC-Ssc-115535 Sus scrofa 93.16 0.00e+00 3456.00
IUUC-Tgu-117493 Taeniopygia guttata 90.62 0.00e+00 2689.00
IUUC-Tru-118669 Takifugu rubripes 80.23 0.00e+00 3007.00
IUUC-Tsy-119373 Tarsius syrichta 94.75 0.00e+00 1869.00
IUUC-Tni-120049 Tetraodon nigroviridis 77.98 0.00e+00 867.00
IUUC-Tca-121779 Theobroma cacao 38.76 1.00e-115 412.00
IUUC-Tre-122195 Trichoderma reesei 35.80 2.00e-105 378.00
IUUC-Tvi-122650 Trichoderma virens 35.93 4.00e-109 390.00
IUUC-Tae-123580 Triticum aestivum 38.58 2.00e-124 440.00
IUUC-Tur-126295 Triticum urartu 38.54 2.00e-125 444.00
IUUC-Tme-126964 Tuber melanosporum 40.48 1.00e-105 378.00
IUUC-Tbe-128149 Tupaia belangeri 81.95 0.00e+00 1467.00
IUUC-Ttr-128165 Tursiops truncatus 94.81 0.00e+00 3063.00
IUUC-Uma-129365 Ustilago maydis 36.07 7.00e-89 323.00
IUUC-Vda-129725 Verticillium dahliae 41.08 6.00e-109 389.00
IUUC-Vpa-130678 Vicugna pacos 98.91 0.00e+00 2692.00
IUUC-Vvi-131147 Vitis vinifera 39.23 2.00e-122 434.00
IUUC-Xtr-132636 Xenopus tropicalis 87.43 0.00e+00 3265.00
IUUC-Xma-133458 Xiphophorus maculatus 79.87 0.00e+00 3061.00
IUUC-Yli-134481 Yarrowia lipolytica 39.56 7.00e-98 352.00
IUUC-Zma-135782 Zea mays 37.87 6.00e-118 419.00
Created Date 25-Jun-2017

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