TRIM2_MOUSE
ID TRIM2_MOUSE Reviewed; 744 AA.
AC Q9ESN6; Q3UHP5; Q5DU27; Q8C981;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Tripartite motif-containing protein 2;
DE EC=2.3.2.27;
DE AltName: Full=E3 ubiquitin-protein ligase TRIM2;
DE AltName: Full=Neural activity-related RING finger protein;
DE AltName: Full=RING-type E3 ubiquitin transferase TRIM2 {ECO:0000305};
GN Name=Trim2; Synonyms=Kiaa0517, Narf;
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], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=ICR; TISSUE=Hippocampus;
RX PubMed=11432975; DOI=10.1046/j.1471-4159.2001.00373.x;
RA Ohkawa N., Kokura K., Matsu-ura T., Obinata T., Konishi Y., Tamura T.-A.;
RT "Molecular cloning and characterization of neural activity-related RING
RT finger protein (NARF): a new member of the RBCC family is a candidate for
RT the partner of myosin V.";
RL J. Neurochem. 78:75-87(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11331580; DOI=10.1093/emboj/20.9.2140;
RA Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L.,
RA Riganelli D., Zanaria E., Messali S., Cainarca S., Guffanti A., Minucci S.,
RA Pelicci P.G., Ballabio A.;
RT "The tripartite motif family identifies cell compartments.";
RL EMBO J. 20:2140-2151(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Bone, Cerebellum, Corpora quadrigemina, and Spinal cord;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [6]
RP FUNCTION, INTERACTION WITH NEFL, AUTOUBIQUITINATION, DISRUPTION PHENOTYPE,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=18687884; DOI=10.1073/pnas.0802261105;
RA Balastik M., Ferraguti F., Pires-da Silva A., Lee T.H., Alvarez-Bolado G.,
RA Lu K.P., Gruss P.;
RT "Deficiency in ubiquitin ligase TRIM2 causes accumulation of neurofilament
RT light chain and neurodegeneration.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12016-12021(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-371; SER-375; SER-424 AND
RP SER-428, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, and Kidney;
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).
RN [8]
RP FUNCTION, AND INTERACTION WITH BCL2L11.
RX PubMed=21478148; DOI=10.1074/jbc.m110.197707;
RA Thompson S., Pearson A.N., Ashley M.D., Jessick V., Murphy B.M., Gafken P.,
RA Henshall D.C., Morris K.T., Simon R.P., Meller R.;
RT "Identification of a novel Bcl-2-interacting mediator of cell death (Bim)
RT E3 ligase, tripartite motif-containing protein 2 (TRIM2), and its role in
RT rapid ischemic tolerance-induced neuroprotection.";
RL J. Biol. Chem. 286:19331-19339(2011).
CC -!- FUNCTION: UBE2D1-dependent E3 ubiquitin-protein ligase that mediates
CC the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a
CC neuroprotective function. May play a role in neuronal rapid ischemic
CC tolerance. {ECO:0000269|PubMed:18687884, ECO:0000269|PubMed:21478148}.
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;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with myosin V; myosin V may not be a substrate for
CC ubiquitination. Interacts with NEFL. Interacts with phosphorylated
CC BCL2L11. {ECO:0000269|PubMed:18687884, ECO:0000269|PubMed:21478148}.
CC -!- INTERACTION:
CC Q9ESN6; P08551: Nefl; NbExp=2; IntAct=EBI-8315064, EBI-445199;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11432975}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the cerebellum, hippocampus,
CC retina and spinal cord. In the cerebellum, strongest expression in
CC Purkinje cells and in the deep cerebellar nuclei. In retina, high
CC expression in the ganglionic cell layer, inner nuclear layer and inthe
CC outer plexiform layer. Particularly high expression in the hippocampus,
CC in pyramidal cells of CA1-CA3 hippocampal areas and ingranule cells of
CC the dentate gyrus. {ECO:0000269|PubMed:11432975,
CC ECO:0000269|PubMed:18687884}.
CC -!- DEVELOPMENTAL STAGE: At 12.5 dpc, expressed in the developing nervous
CC system, particularly in the spinal cord, dorsal rootganglia, hindbrain
CC and midbrain. {ECO:0000269|PubMed:18687884}.
CC -!- DOMAIN: The interaction with myosin V is dependent upon its NHL
CC repeats, which form a beta-propeller (NHL) domain containing six
CC blades.
CC -!- PTM: RING-type zinc finger-dependent and UBE2D1-dependent
CC autoubiquitination. {ECO:0000269|PubMed:18687884}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are indistinguishable from wild type
CC until about 1.5 months of age, when they begin to show intention
CC tremor, followed by gait ataxia. At this stage, neurons exhibit axonal
CC swellings, which consist of the accumulation of disorganized
CC neurofilaments and microtubules, mitochondria and vesicles. In later
CC stages, mutant animals suffer from episodes of spontaneous generalized
CC seizures, a phenotype caused by progressive loss of Purkinje cells
CC through apoptosis. At 4 months of age, retinas in mutant mice display
CC decreased thickness of the inner nuclear layer and a reduced number of
CC ganglionic cells. The outer plexiform layer is also reduced, whereas
CC the size of the photoreceptor layer is not altered.
CC {ECO:0000269|PubMed:18687884}.
CC -!- SIMILARITY: Belongs to the TRIM/RBCC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD90242.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB043550; BAB17634.1; -; mRNA.
DR EMBL; AF220017; AAG53471.1; -; mRNA.
DR EMBL; AK042752; BAC31352.1; -; mRNA.
DR EMBL; AK045410; BAC32350.1; -; mRNA.
DR EMBL; AK079415; BAC37640.1; -; mRNA.
DR EMBL; AK147275; BAE27812.1; -; mRNA.
DR EMBL; AK220343; BAD90242.1; ALT_INIT; mRNA.
DR EMBL; BC058961; AAH58961.1; -; mRNA.
DR CCDS; CCDS71256.1; -.
DR RefSeq; NP_001258654.1; NM_001271725.1.
DR RefSeq; NP_001258655.1; NM_001271726.1.
DR RefSeq; NP_001258656.1; NM_001271727.1.
DR RefSeq; NP_001258657.1; NM_001271728.1.
DR RefSeq; NP_109631.2; NM_030706.3.
DR RefSeq; XP_017175303.1; XM_017319814.1.
DR AlphaFoldDB; Q9ESN6; -.
DR SMR; Q9ESN6; -.
DR BioGRID; 219833; 12.
DR DIP; DIP-46254N; -.
DR IntAct; Q9ESN6; 1.
DR STRING; 10090.ENSMUSP00000069922; -.
DR iPTMnet; Q9ESN6; -.
DR PhosphoSitePlus; Q9ESN6; -.
DR SwissPalm; Q9ESN6; -.
DR MaxQB; Q9ESN6; -.
DR PaxDb; Q9ESN6; -.
DR PRIDE; Q9ESN6; -.
DR ProteomicsDB; 258979; -.
DR DNASU; 80890; -.
DR Ensembl; ENSMUST00000065380; ENSMUSP00000069922; ENSMUSG00000027993.
DR Ensembl; ENSMUST00000107691; ENSMUSP00000103319; ENSMUSG00000027993.
DR Ensembl; ENSMUST00000107692; ENSMUSP00000103320; ENSMUSG00000027993.
DR Ensembl; ENSMUST00000107693; ENSMUSP00000103321; ENSMUSG00000027993.
DR GeneID; 80890; -.
DR KEGG; mmu:80890; -.
DR UCSC; uc008ppx.3; mouse.
DR CTD; 23321; -.
DR MGI; MGI:1933163; Trim2.
DR VEuPathDB; HostDB:ENSMUSG00000027993; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00940000155905; -.
DR HOGENOM; CLU_008645_5_0_1; -.
DR InParanoid; Q9ESN6; -.
DR OrthoDB; 489543at2759; -.
DR PhylomeDB; Q9ESN6; -.
DR TreeFam; TF331018; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 80890; 3 hits in 70 CRISPR screens.
DR ChiTaRS; Trim2; mouse.
DR PRO; PR:Q9ESN6; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9ESN6; protein.
DR Bgee; ENSMUSG00000027993; Expressed in rostral migratory stream and 268 other tissues.
DR ExpressionAtlas; Q9ESN6; baseline and differential.
DR Genevisible; Q9ESN6; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0017022; F:myosin binding; NAS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IMP:UniProtKB.
DR Gene3D; 2.120.10.30; -; 2.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR003649; Bbox_C.
DR InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR InterPro; IPR001298; Filamin/ABP280_rpt.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR001258; NHL_repeat.
DR InterPro; IPR027370; Znf-RING_LisH.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00630; Filamin; 1.
DR Pfam; PF01436; NHL; 6.
DR Pfam; PF00643; zf-B_box; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR SMART; SM00502; BBC; 1.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00557; IG_FLMN; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS50194; FILAMIN_REPEAT; 1.
DR PROSITE; PS51125; NHL; 6.
DR PROSITE; PS50119; ZF_BBOX; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Metal-binding; Phosphoprotein; Reference proteome; Repeat;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..744
FT /note="Tripartite motif-containing protein 2"
FT /id="PRO_0000056196"
FT REPEAT 320..421
FT /note="Filamin"
FT REPEAT 473..516
FT /note="NHL 1"
FT REPEAT 520..563
FT /note="NHL 2"
FT REPEAT 564..605
FT /note="NHL 3"
FT REPEAT 609..652
FT /note="NHL 4"
FT REPEAT 656..699
FT /note="NHL 5"
FT REPEAT 700..743
FT /note="NHL 6"
FT ZN_FING 23..64
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 113..154
FT /note="B box-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT REGION 432..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 146
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:D3ZQG6"
FT MOD_RES 371
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 744 AA; 81445 MW; 80336DA2EFEE5EFD CRC64;
MASEGASIPS PVVRQIDKQF LICSICLERY KNPKVLPCLH TFCERCLQNY IPAHSLTLSC
PVCRQTSILP EKGVAALQNN FFITNLMDVL QRTPGSNGED SSILETVTAV AAGKPLSCPN
HDGNVMEFYC QSCETAMCRE CTEGEHAEHP TVPLKDVVEQ HKASLQVQLD AVNKRLPEID
SALQFISEII HQLTNQKASI VDDIHSTFDE LQKTLNVRKS VLLMELEVNY GLKHKVLQSQ
LDTLLQGQES IKSCSNFTAQ ALNHGTETEV LLVKKQMSEK LNELADQDFP LHPRENDQLD
FIVETEGLKK SIHNLGTILT TNAVASETVA TGEGLRQTII GQPMSVTITT KDKDGELCKT
GNAYLTAELS TPDGSVADGE ILDNKNGTYE FLYTVQKEGD FTLSLRLYDQ HIRGSPFKLK
VIRSADVSPT TEGVKRRVKS PGSGHVKQKA VKRPASMYST GKRKENPIED DLIFRVGTKG
RNKGEFTNLQ GVAASTSGKI LIADSNNQCV QIFSNDGQFK SRFGIRGRSP GQLQRPTGVA
VHPSGDIIIA DYDNKWVSIF SNDGKFKTKI GSGKLMGPKG VSVDRNGHII VVDNKACCVF
IFQPNGKIVT RFGSRGNGDR QFAGPHFAAV NSNNEIIITD FHNHSVKVFN QEGEFMLKFG
SNGEGNGQFN APTGVAVDSN GNIIVADWGN SRIQVFDGSG SFLSYINTSA DPLYGPQGLA
LTSDGHVVVA DSGNHCFKVY RYLQ
