TRAIP_MOUSE
ID TRAIP_MOUSE Reviewed; 470 AA.
AC Q8VIG6; O08854; Q922M8; Q9CPP4;
DT 09-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 09-MAY-2003, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=E3 ubiquitin-protein ligase TRAIP {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:17544371, ECO:0000269|PubMed:22945920};
DE AltName: Full=TRAF-interacting protein {ECO:0000303|PubMed:9104814};
GN Name=Traip {ECO:0000303|PubMed:27405720, ECO:0000312|MGI:MGI:1096377};
GN Synonyms=Trip {ECO:0000303|PubMed:9104814};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH TRAF1 AND TRAF2,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Thymocyte;
RX PubMed=9104814; DOI=10.1084/jem.185.7.1275;
RA Lee S.Y., Lee S.Y., Choi Y.;
RT "TRAF-interacting protein (TRIP): a novel component of the tumor necrosis
RT factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits
RT TRAF2-mediated NF-kappaB activation.";
RL J. Exp. Med. 185:1275-1285(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Mammary cancer;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AUTOUBIQUITINATION, MUTAGENESIS OF CYS-7, AND INTERACTION WITH
RP TRAF1; TRAF2; TRAF3; TRAF5 AND TRAF6.
RX PubMed=17544371; DOI=10.1016/j.bbrc.2007.05.149;
RA Besse A., Campos A.D., Webster W.K., Darnay B.G.;
RT "TRAF-interacting protein (TRIP) is a RING-dependent ubiquitin ligase.";
RL Biochem. Biophys. Res. Commun. 359:660-664(2007).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=17927961; DOI=10.1016/j.bbrc.2007.09.103;
RA Park E.S., Choi S., Kim J.M., Jeong Y., Choe J., Park C.S., Choi Y.,
RA Rho J.;
RT "Early embryonic lethality caused by targeted disruption of the TRAF-
RT interacting protein (TRIP) gene.";
RL Biochem. Biophys. Res. Commun. 363:971-977(2007).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22945920; DOI=10.1084/jem.20120024;
RA Zhang M., Wang L., Zhao X., Zhao K., Meng H., Zhao W., Gao C.;
RT "TRAF-interacting protein (TRIP) negatively regulates IFN-beta production
RT and antiviral response by promoting proteasomal degradation of TANK-binding
RT kinase 1.";
RL J. Exp. Med. 209:1703-1711(2012).
RN [7]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=27405720; DOI=10.1038/srep29735;
RA Yuan Y.F., Ren Y.X., Yuan P., Yan L.Y., Qiao J.;
RT "TRAIP is involved in chromosome alignment and SAC regulation in mouse
RT oocyte meiosis.";
RL Sci. Rep. 6:29735-29735(2016).
CC -!- FUNCTION: E3 ubiquitin ligase required to protect genome stability in
CC response to replication stress (By similarity). Acts as a key regulator
CC of interstrand cross-link repair, which takes place when both strands
CC of duplex DNA are covalently tethered together, thereby blocking
CC replication and transcription (By similarity). Controls the choice
CC between the two pathways of replication-coupled interstrand-cross-link
CC repair by mediating ubiquitination of MCM7 subunit of the CMG helicase
CC complex (By similarity). Short ubiquitin chains on MCM7 promote
CC recruitment of DNA glycosylase NEIL3 (By similarity). If the
CC interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains
CC continue to grow on MCM7, promoting the unloading of the CMG helicase
CC complex by the VCP/p97 ATPase, enabling the Fanconi anemia DNA repair
CC pathway (By similarity). Only catalyzes ubiquitination of MCM7 when
CC forks converge (By similarity). Also involved in the repair of covalent
CC DNA-protein cross-links (DPCs) during DNA synthesis: promotes
CC ubiquitination of DPCs, leading to their degradation by the proteasome
CC (By similarity). Has also been proposed to play a role in promoting
CC translesion synthesis by mediating the assembly of 'Lys-63'-linked
CC poly-ubiquitin chains on the Y-family polymerase POLN in order to
CC facilitate bypass of DNA lesions and preserve genomic integrity (By
CC similarity). The function in translesion synthesis is however
CC controversial (By similarity). Acts as a regulator of the spindle
CC assembly checkpoint (By similarity). Also acts as a negative regulator
CC of innate immune signaling by inhibiting activation of NF-kappa-B
CC mediated by TNF (PubMed:17544371, PubMed:22945920). Negatively
CC regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent
CC IFNB1 production and cellular antiviral response by promoting 'Lys-48'-
CC linked polyubiquitination of TNK1 leading to its proteasomal
CC degradation (By similarity). {ECO:0000250|UniProtKB:Q6NRV0,
CC ECO:0000250|UniProtKB:Q9BWF2, ECO:0000269|PubMed:17544371,
CC ECO:0000269|PubMed:22945920}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:17544371,
CC ECO:0000269|PubMed:22945920};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:17544371, ECO:0000269|PubMed:22945920}.
CC -!- SUBUNIT: Interacts (via PIP-box) with PCNA (By similarity). Binds
CC TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6 is part of the receptor-TRAF
CC signaling complex (PubMed:17544371, PubMed:9104814). May interact with
CC CYLD; the C-terminus interacts with CYLD, however the interaction was
CC not detected with the full-length protein (By similarity). Interacts
CC with POLK and POLN (By similarity). Interacts with UIMC1 (By
CC similarity). {ECO:0000250|UniProtKB:Q9BWF2,
CC ECO:0000269|PubMed:17544371, ECO:0000269|PubMed:9104814}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q9BWF2}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q9BWF2}. Chromosome
CC {ECO:0000269|PubMed:27405720}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9BWF2}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q9BWF2}. Note=In the nucleus, found in close
CC proximity to PCNA, suggesting localization at replication foci.
CC Localizes to DNA damage sites in response to replication stress.
CC {ECO:0000250|UniProtKB:Q9BWF2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VIG6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VIG6-2; Sequence=VSP_007406, VSP_007407;
CC -!- TISSUE SPECIFICITY: Detected in testis and thymus, and at lower levels
CC in spleen. {ECO:0000269|PubMed:9104814}.
CC -!- DEVELOPMENTAL STAGE: Expressed during oocytes meiosis.
CC {ECO:0000269|PubMed:27405720}.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:17544371}.
CC -!- PTM: Sumoylated; sumoylation is required for nuclear localization.
CC Sumoylation increases protein stability, possibly by preventing
CC ubiquitination. {ECO:0000250|UniProtKB:Q9BWF2}.
CC -!- DISRUPTION PHENOTYPE: Early embryonic lethality due to proliferation
CC defects and excessive cell death (PubMed:17927961). TRAIP knockdown
CC substantially increases LPS- and poly(I:C)-induced IFN-production in
CC mouse peritoneal macrophages at both mRNA and protein levels
CC (PubMed:22945920). {ECO:0000269|PubMed:17927961,
CC ECO:0000269|PubMed:22945920}.
CC -!- SIMILARITY: Belongs to the TRAIP family. {ECO:0000305}.
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DR EMBL; U77844; AAB52994.1; -; mRNA.
DR EMBL; AK012786; BAB28469.1; -; mRNA.
DR EMBL; AK012948; BAB28567.1; -; mRNA.
DR EMBL; BC006929; AAH06929.1; -; mRNA.
DR EMBL; BC017374; AAH17374.1; -; mRNA.
DR CCDS; CCDS23511.1; -. [Q8VIG6-1]
DR RefSeq; NP_035764.2; NM_011634.3. [Q8VIG6-1]
DR AlphaFoldDB; Q8VIG6; -.
DR SMR; Q8VIG6; -.
DR BioGRID; 204309; 3.
DR STRING; 10090.ENSMUSP00000040001; -.
DR iPTMnet; Q8VIG6; -.
DR PhosphoSitePlus; Q8VIG6; -.
DR EPD; Q8VIG6; -.
DR jPOST; Q8VIG6; -.
DR MaxQB; Q8VIG6; -.
DR PaxDb; Q8VIG6; -.
DR PRIDE; Q8VIG6; -.
DR ProteomicsDB; 298283; -. [Q8VIG6-1]
DR ProteomicsDB; 298284; -. [Q8VIG6-2]
DR Antibodypedia; 30670; 309 antibodies from 32 providers.
DR DNASU; 22036; -.
DR Ensembl; ENSMUST00000049348; ENSMUSP00000040001; ENSMUSG00000032586. [Q8VIG6-1]
DR GeneID; 22036; -.
DR KEGG; mmu:22036; -.
DR UCSC; uc009rnn.1; mouse. [Q8VIG6-1]
DR CTD; 10293; -.
DR MGI; MGI:1096377; Traip.
DR VEuPathDB; HostDB:ENSMUSG00000032586; -.
DR eggNOG; KOG0827; Eukaryota.
DR GeneTree; ENSGT00390000007696; -.
DR HOGENOM; CLU_046426_0_0_1; -.
DR InParanoid; Q8VIG6; -.
DR OMA; VMIRPLP; -.
DR OrthoDB; 761263at2759; -.
DR PhylomeDB; Q8VIG6; -.
DR TreeFam; TF317309; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 22036; 26 hits in 73 CRISPR screens.
DR ChiTaRS; Traip; mouse.
DR PRO; PR:Q8VIG6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8VIG6; protein.
DR Bgee; ENSMUSG00000032586; Expressed in embryonic post-anal tail and 183 other tissues.
DR ExpressionAtlas; Q8VIG6; baseline and differential.
DR Genevisible; Q8VIG6; MM.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:FlyBase.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0032688; P:negative regulation of interferon-beta production; IDA:CACAO.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:MGI.
DR GO; GO:0010804; P:negative regulation of tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IDA:FlyBase.
DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; ISS:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IDA:MGI.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosome; Coiled coil; Cytoplasm; DNA damage;
KW DNA repair; Metal-binding; Nucleus; Reference proteome; Repeat;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..470
FT /note="E3 ubiquitin-protein ligase TRAIP"
FT /id="PRO_0000056192"
FT ZN_FING 7..50
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 211..470
FT /note="Interaction with CYLD"
FT /evidence="ECO:0000250|UniProtKB:Q9BWF2"
FT COILED 76..277
FT /evidence="ECO:0000255"
FT MOTIF 461..470
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9BWF2"
FT VAR_SEQ 207..223
FT /note="EYENLKEARKATGELAD -> CVSSGVPLPSSFVMQIL (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007406"
FT VAR_SEQ 224..470
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007407"
FT MUTAGEN 7
FT /note="C->A: Fails to autoubiquitinate."
FT /evidence="ECO:0000269|PubMed:17544371"
FT CONFLICT 4..5
FT /note="RA -> LS (in Ref. 1; AAB52994)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="T -> M (in Ref. 3; AAH17374)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="A -> R (in Ref. 1; AAB52994)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="C -> S (in Ref. 1; AAB52994)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 470 AA; 53149 MW; EBFABC49A9F4BF2E CRC64;
MPIRALCTIC SDFFDHSRDV AAIHCGHTFH LQCLIQWFET APSRTCPQCR IQVGKKTIIN
KLFFDLAQEE ENVLDAEFLK NELDSVKAQL SQKDREKRDS QAIIDTLRDT LEERNATVES
LQNALNKAEM LCSTLKKQMK FLEQRQDETK QAREEAHRLK CKMKTMEQIE LLLQSQRSEV
EEMIRDMGVG QSAVEQLAVY CVSLKKEYEN LKEARKATGE LADRLKKDLV SSRSKLKTLN
TELDQAKLEL RSAQKDLQSA DQEITSLRKK LMILQGTLSL PPATNETVSR LVFESPAPVE
MMNPRLHQPP FGDEIDLNTT FDVNTPPTQT SGSQHCLPKK LCLERARSPM QNVLKKVHKV
SKPESQLSLG GQRCVGELDE ELAGAFPLFI RNAVLGQKQP NRTTAESRCS TDVVRIGFDG
LGGRTKFIQP RDTTIIRPVP VKSKAKSKQK VRIKTVSSAS QPKLDTFLCQ
