TRAD1_MOUSE
ID TRAD1_MOUSE Reviewed; 580 AA.
AC Q3UDK1; Q8CFI8;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=TRAF-type zinc finger domain-containing protein 1;
DE AltName: Full=Protein FLN29;
GN Name=Trafd1; Synonyms=Fln29;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor;
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 [3]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, INTERACTION WITH TRAF6, AND
RP MUTAGENESIS OF GLU-294.
RX PubMed=16221674; DOI=10.1074/jbc.m508221200;
RA Mashima R., Saeki K., Aki D., Minoda Y., Takaki H., Sanada T.,
RA Kobayashi T., Aburatani H., Yamanashi Y., Yoshimura A.;
RT "FLN29, a novel interferon- and LPS-inducible gene acting as a negative
RT regulator of toll-like receptor signaling.";
RL J. Biol. Chem. 280:41289-41297(2005).
RN [4]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INTERACTION WITH MAVS; TICAM1; TRAF1;
RP TRAF2; TRAF3 AND TRAF6.
RX PubMed=18849341; DOI=10.1074/jbc.m806923200;
RA Sanada T., Takaesu G., Mashima R., Yoshida R., Kobayashi T., Yoshimura A.;
RT "FLN29 deficiency reveals its negative regulatory role in the Toll-like
RT receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like helicase
RT signaling pathway.";
RL J. Biol. Chem. 283:33858-33864(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Negative feedback regulator that controls excessive innate
CC immune responses. Regulates both Toll-like receptor 4 (TLR4) and
CC DDX58/RIG1-like helicases (RLH) pathways. May inhibit the LTR pathway
CC by direct interaction with TRAF6 and attenuation of NF-kappa-B
CC activation. May negatively regulate the RLH pathway downstream from
CC MAVS and upstream of NF-kappa-B and IRF3. {ECO:0000269|PubMed:16221674,
CC ECO:0000269|PubMed:18849341}.
CC -!- SUBUNIT: Interacts with MAVS, TICAM1, TRAF1, TRAF2, TRAF3 and TRAF6.
CC {ECO:0000269|PubMed:16221674, ECO:0000269|PubMed:18849341}.
CC -!- INTERACTION:
CC Q3UDK1; P70196: Traf6; NbExp=2; IntAct=EBI-1396948, EBI-448028;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UDK1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UDK1-2; Sequence=VSP_023294;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, brain, liver, kidney,
CC spleen and bone marrow. Expression depends on STAT1.
CC {ECO:0000269|PubMed:16221674}.
CC -!- INDUCTION: By lipopolysaccharide (LPS), IFNB1 and IFNG, IFNB1 being
CC most rapid and potent inducer (at protein level). Not induced by anti-
CC inflammatory cytokines, such as IL4 and IL10, which also inhibit LPS
CC induction of TRAFD1. {ECO:0000269|PubMed:16221674}.
CC -!- DISRUPTION PHENOTYPE: Mice show no gross developmental abnormalities,
CC but exhibit an increased susceptibility to LPS-induced septic shock and
CC are more sensitive to poly(I:C) shock, suffering more severe hepatic
CC damage than wild-type animals. In response to LPS-stimulation, bone
CC marrow-derived dendritic cells display an increased production of pro-
CC inflammatory cytokines, such as IL6, TNF and IL12, as well as elevated
CC IKK and JNK activation, compared to wild-type mice. Mutant embryonic
CC fibroblasts are more resistant to vesicular stomatitis virus (VSV)-
CC induced cytopathic effect. {ECO:0000269|PubMed:18849341}.
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DR EMBL; AK150038; BAE29260.1; -; mRNA.
DR EMBL; BC038396; AAH38396.1; -; mRNA.
DR CCDS; CCDS51638.1; -. [Q3UDK1-1]
DR CCDS; CCDS51639.1; -. [Q3UDK1-2]
DR RefSeq; NP_001156942.1; NM_001163470.1. [Q3UDK1-1]
DR RefSeq; NP_758479.2; NM_172275.2. [Q3UDK1-2]
DR RefSeq; XP_006530365.1; XM_006530302.3. [Q3UDK1-1]
DR RefSeq; XP_011246499.1; XM_011248197.2. [Q3UDK1-1]
DR RefSeq; XP_017176353.1; XM_017320864.1. [Q3UDK1-1]
DR RefSeq; XP_017176354.1; XM_017320865.1. [Q3UDK1-2]
DR RefSeq; XP_017176355.1; XM_017320866.1.
DR AlphaFoldDB; Q3UDK1; -.
DR BioGRID; 231158; 1.
DR IntAct; Q3UDK1; 3.
DR MINT; Q3UDK1; -.
DR STRING; 10090.ENSMUSP00000047475; -.
DR iPTMnet; Q3UDK1; -.
DR PhosphoSitePlus; Q3UDK1; -.
DR EPD; Q3UDK1; -.
DR MaxQB; Q3UDK1; -.
DR PaxDb; Q3UDK1; -.
DR PeptideAtlas; Q3UDK1; -.
DR PRIDE; Q3UDK1; -.
DR ProteomicsDB; 297519; -. [Q3UDK1-1]
DR ProteomicsDB; 297520; -. [Q3UDK1-2]
DR Antibodypedia; 18647; 221 antibodies from 26 providers.
DR DNASU; 231712; -.
DR Ensembl; ENSMUST00000042312; ENSMUSP00000047475; ENSMUSG00000042726. [Q3UDK1-1]
DR Ensembl; ENSMUST00000120784; ENSMUSP00000113910; ENSMUSG00000042726. [Q3UDK1-2]
DR GeneID; 231712; -.
DR KEGG; mmu:231712; -.
DR UCSC; uc008ziy.2; mouse. [Q3UDK1-2]
DR UCSC; uc008ziz.2; mouse. [Q3UDK1-1]
DR CTD; 10906; -.
DR MGI; MGI:1923551; Trafd1.
DR VEuPathDB; HostDB:ENSMUSG00000042726; -.
DR eggNOG; ENOG502QQRU; Eukaryota.
DR GeneTree; ENSGT00530000063869; -.
DR HOGENOM; CLU_034057_0_0_1; -.
DR InParanoid; Q3UDK1; -.
DR OMA; AHQSSEC; -.
DR OrthoDB; 1113262at2759; -.
DR PhylomeDB; Q3UDK1; -.
DR TreeFam; TF331416; -.
DR BioGRID-ORCS; 231712; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Trafd1; mouse.
DR PRO; PR:Q3UDK1; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q3UDK1; protein.
DR Bgee; ENSMUSG00000042726; Expressed in spermatocyte and 258 other tissues.
DR ExpressionAtlas; Q3UDK1; baseline and differential.
DR Genevisible; Q3UDK1; MM.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0045824; P:negative regulation of innate immune response; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001293; Znf_TRAF.
DR PROSITE; PS50145; ZF_TRAF; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Metal-binding; Phosphoprotein;
KW Reference proteome; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT CHAIN 2..580
FT /note="TRAF-type zinc finger domain-containing protein 1"
FT /id="PRO_0000278459"
FT ZN_FING 27..103
FT /note="TRAF-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00207"
FT REGION 395..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 468..509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 415..431
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 480..503
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MM4"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14545"
FT MOD_RES 532
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MM4"
FT VAR_SEQ 535..539
FT /note="RYGAG -> S (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023294"
FT MUTAGEN 294
FT /note="E->A: No effect on TRAF6-induced NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:16221674"
FT CONFLICT 328
FT /note="I -> V (in Ref. 2; AAH38396)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="V -> M (in Ref. 2; AAH38396)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 580 AA; 64283 MW; ADDABA43305FB70B CRC64;
MAEFRDDQAS RLCDNCKKEI PVFNFTIHEI HCQRNIGVCP VCKEPFPKSD MDIHMAAEHC
QVTCKCNKKL EKRQLKQHAE TECPLRLAVC QHCDLELSVV KLKEHEDYCG ARTELCGSCG
RNVLVKELKT HPEVCGRVEE EKRTEAAIPP EAYDEPWSQD RIWIASQLLR QIEALDPPMR
LPGRPLQAFE ADPFYSRTTS QRSMAAQFPV QNNLFEEQER QERNRSRQSP KDSAENNAHL
DFMLALSLQN EGQATSMVEQ GFWESVPEAD PARAGPTSLG DIKGAADEIL LPCEFCEELY
PEELLIDHQT SCNPSHALRS LNTGSSSIRG VEDPGTIFQN FLQQATSNQF DTLMGLSSSA
AVEDSIIIPC EFCGVQLEEE VLFYHQDQCD QRPATANHRA VEGIPAQDSQ PENTSAELSR
RRVKHQGDLS SGYMDDVKPE SVKGPTYSMS PNRTMNNVAS CNRLLNLPSG PRSDCQRSPP
GVLKLNNSDS QDIRGQMRGS QNGPIASGHA PVIHSIQNLY PENFAPSFPH GSPGRYGAGG
RSEGGRSSRV SPAAAGYHSR AAKAKPPKQQ GAGDAEEEEE
