TRAIP_XENLA
ID TRAIP_XENLA Reviewed; 464 AA.
AC Q6NRV0; A0A1L8GP65;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 02-DEC-2020, sequence version 2.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=E3 ubiquitin-protein ligase TRAIP {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:30842657, ECO:0000269|PubMed:30979826};
DE AltName: Full=TRAF-interacting protein {ECO:0000303|PubMed:30842657};
GN Name=traip {ECO:0000303|PubMed:30842657};
GN ORFNames=XELAEV_18023818mg {ECO:0000312|EMBL:OCT85647.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH70612.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|Proteomes:UP000186698}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=J;
RX PubMed=27762356; DOI=10.1038/nature19840;
RA Session A.M., Uno Y., Kwon T., Chapman J.A., Toyoda A., Takahashi S.,
RA Fukui A., Hikosaka A., Suzuki A., Kondo M., van Heeringen S.J., Quigley I.,
RA Heinz S., Ogino H., Ochi H., Hellsten U., Lyons J.B., Simakov O.,
RA Putnam N., Stites J., Kuroki Y., Tanaka T., Michiue T., Watanabe M.,
RA Bogdanovic O., Lister R., Georgiou G., Paranjpe S.S., van Kruijsbergen I.,
RA Shu S., Carlson J., Kinoshita T., Ohta Y., Mawaribuchi S., Jenkins J.,
RA Grimwood J., Schmutz J., Mitros T., Mozaffari S.V., Suzuki Y., Haramoto Y.,
RA Yamamoto T.S., Takagi C., Heald R., Miller K., Haudenschild C., Kitzman J.,
RA Nakayama T., Izutsu Y., Robert J., Fortriede J., Burns K., Lotay V.,
RA Karimi K., Yasuoka Y., Dichmann D.S., Flajnik M.F., Houston D.W.,
RA Shendure J., DuPasquier L., Vize P.D., Zorn A.M., Ito M., Marcotte E.M.,
RA Wallingford J.B., Ito Y., Asashima M., Ueno N., Matsuda Y., Veenstra G.J.,
RA Fujiyama A., Harland R.M., Taira M., Rokhsar D.S.;
RT "Genome evolution in the allotetraploid frog Xenopus laevis.";
RL Nature 538:336-343(2016).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=26711499; DOI=10.1083/jcb.201506071;
RA Hoffmann S., Smedegaard S., Nakamura K., Mortuza G.B., Raschle M.,
RA Ibanez de Opakua A., Oka Y., Feng Y., Blanco F.J., Mann M., Montoya G.,
RA Groth A., Bekker-Jensen S., Mailand N.;
RT "TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability
RT after replication stress.";
RL J. Cell Biol. 212:63-75(2016).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-25.
RX PubMed=30979826; DOI=10.26508/lsa.201900390;
RA Priego Moreno S., Jones R.M., Poovathumkadavil D., Scaramuzza S.,
RA Gambus A.;
RT "Mitotic replisome disassembly depends on TRAIP ubiquitin ligase
RT activity.";
RL Life. Sci Alliance 2:0-0(2019).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF ARG-18 AND 456-GLN--LYS-464.
RX PubMed=30849395; DOI=10.1016/j.molcel.2018.12.021;
RA Deng L., Wu R.A., Sonneville R., Kochenova O.V., Labib K., Pellman D.,
RA Walter J.C.;
RT "Mitotic CDK Promotes replisome disassembly, fork breakage, and complex DNA
RT rearrangements.";
RL Mol. Cell 73:915-929(2019).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-18 AND
RP 456-GLN--LYS-464.
RX PubMed=30842657; DOI=10.1038/s41586-019-1002-0;
RA Wu R.A., Semlow D.R., Kamimae-Lanning A.N., Kochenova O.V., Chistol G.,
RA Hodskinson M.R., Amunugama R., Sparks J.L., Wang M., Deng L., Mimoso C.A.,
RA Low E., Patel K.J., Walter J.C.;
RT "TRAIP is a master regulator of DNA interstrand crosslink repair.";
RL Nature 567:267-272(2019).
RN [7]
RP FUNCTION, AND MUTAGENESIS OF ARG-18.
RX PubMed=30595436; DOI=10.1016/j.molcel.2018.11.024;
RA Larsen N.B., Gao A.O., Sparks J.L., Gallina I., Wu R.A., Mann M.,
RA Raeschle M., Walter J.C., Duxin J.P.;
RT "Replication-coupled DNA-protein crosslink repair by SPRTN and the
RT proteasome in Xenopus egg extracts.";
RL Mol. Cell 73:574-588(2019).
CC -!- FUNCTION: E3 ubiquitin ligase required to protect genome stability in
CC response to replication stress (PubMed:30979826, PubMed:30849395,
CC PubMed:30842657). Acts as a key regulator of interstrand cross-link
CC repair, which takes place when both strands of duplex DNA are
CC covalently tethered together, thereby blocking replication and
CC transcription (PubMed:30979826, PubMed:30849395, PubMed:30842657).
CC Controls the choice between the two pathways of replication-coupled
CC interstrand-cross-link repair by mediating ubiquitination of mcm7
CC subunit of the CMG helicase complex (PubMed:30842657). Short ubiquitin
CC chains on mcm7 promote recruitment of DNA glycosylase neil3
CC (PubMed:30842657). If the interstrand cross-link cannot be cleaved by
CC neil3, the ubiquitin chains continue to grow on mcm7, promoting the
CC unloading of the CMG helicase complex by the vcp/p97 ATPase, enabling
CC the Fanconi anemia DNA repair pathway (PubMed:30979826,
CC PubMed:30842657). Only catalyzes ubiquitination of mcm7 when forks
CC converge (PubMed:30842657). 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 (PubMed:30595436). Also acts as a negative regulator of innate immune
CC signaling by inhibiting activation of NF-kappa-B mediated by TNF (By
CC similarity). {ECO:0000250|UniProtKB:Q9BWF2,
CC ECO:0000269|PubMed:30595436, ECO:0000269|PubMed:30842657,
CC ECO:0000269|PubMed:30849395, ECO:0000269|PubMed:30979826}.
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:30842657,
CC ECO:0000269|PubMed:30979826};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:30842657, ECO:0000269|PubMed:30979826}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q9BWF2}. Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:Q9BWF2}. Chromosome
CC {ECO:0000269|PubMed:26711499, ECO:0000269|PubMed:30842657,
CC ECO:0000269|PubMed:30979826}. Cytoplasm {ECO:0000250|UniProtKB:Q9BWF2}.
CC Note=Localizes to DNA damage sites in response to replication stress.
CC {ECO:0000269|PubMed:26711499, ECO:0000269|PubMed:30842657}.
CC -!- SIMILARITY: Belongs to the TRAIP family. {ECO:0000305}.
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DR EMBL; CM004472; OCT85647.1; -; Genomic_DNA.
DR EMBL; BC070612; AAH70612.1; -; mRNA.
DR RefSeq; NP_001084838.1; NM_001091369.1.
DR AlphaFoldDB; Q6NRV0; -.
DR SMR; Q6NRV0; -.
DR STRING; 8355.A0A1L8GP65; -.
DR DNASU; 431884; -.
DR GeneID; 431884; -.
DR KEGG; xla:431884; -.
DR CTD; 431884; -.
DR Xenbase; XB-GENE-922331; traip.L.
DR OMA; VMIRPLP; -.
DR OrthoDB; 761263at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 431884; Expressed in egg cell and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR GO; GO:1904931; F:MCM complex binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB.
DR GO; GO:0036297; P:interstrand cross-link repair; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; IMP:UniProtKB.
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 Chromosome; Coiled coil; Cytoplasm; DNA damage; DNA repair; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Transferase; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..464
FT /note="E3 ubiquitin-protein ligase TRAIP"
FT /id="PRO_0000451420"
FT ZN_FING 7..50
FT /note="RING-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 439..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 142..186
FT /evidence="ECO:0000255"
FT COILED 236..277
FT /evidence="ECO:0000255"
FT MOTIF 456..464
FT /note="PIP-box"
FT /evidence="ECO:0000269|PubMed:30842657"
FT MUTAGEN 18
FT /note="R->C: Impaired ability to mediate ubiquitination of
FT mcm7. Abolished ability to promote ubiquitination of
FT covalent DNA-protein cross-links (DPCs)."
FT /evidence="ECO:0000269|PubMed:30595436,
FT ECO:0000269|PubMed:30842657, ECO:0000269|PubMed:30849395"
FT MUTAGEN 25
FT /note="C->A: Abolished ability to mediate ubiquitination of
FT mcm7."
FT /evidence="ECO:0000269|PubMed:30979826"
FT MUTAGEN 456..464
FT /note="Missing: Does not affect ability to mediate
FT ubiquitination of mcm7."
FT /evidence="ECO:0000269|PubMed:30842657,
FT ECO:0000269|PubMed:30849395"
FT CONFLICT 17
FT /note="A -> T (in Ref. 1; AAH70612)"
SQ SEQUENCE 464 AA; 52589 MW; 5708C5CB18F061CF CRC64;
MPIRAYCTIC SDFFDNARDV AAITCGHTFH QECLLQWFHS APHRTCPQCR IQVSSRQIIN
KLFFDIGGEE ETVLDAESLK NEVDRIKASL LVKEKEKREC QGLVDSLREM LDVRNVTIQS
QQKELGDMEM LCSTLKKQIK FLDKQQSETK AAKDEARKLR NKLKTMESIE VLLQSQRSEV
EEMIRDMGSG QAAVEQLAIY CVSLKKEYEN LKEVRKSSAE MTEKLRKELF SSNHKAQKAE
LELTKVREEL SASQKELHSA DKEIMSLKKK VEFLQKTLTT PTASNEAISR LIFESPAPIG
LERPKLRPPM MGNDINLDVT FDIDTPEHNT QKSVVAPFKK MKFDNKEHPL SSPTKNPLQE
SKGLMSWAGG RTGADEDDDL TLPSFIKNSL LHKKPVGSLL GLRQNTGAVR TGFDGLGGRT
KFIQPSNLTE IRPLHQKMKR KKVSRPTACT SSLANQPRLE DFLK
