TAB2_RAT
ID TAB2_RAT Reviewed; 693 AA.
AC Q5U303;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=TGF-beta-activated kinase 1 and MAP3K7-binding protein 2;
DE AltName: Full=Mitogen-activated protein kinase kinase kinase 7-interacting protein 2;
DE AltName: Full=TGF-beta-activated kinase 1-binding protein 2;
GN Name=Tab2; Synonyms=Map3k7ip2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Kidney;
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).
CC -!- FUNCTION: Adapter required to activate the JNK and NF-kappa-B signaling
CC pathways through the specific recognition of 'Lys-63'-linked
CC polyubiquitin chains by its RanBP2-type zinc finger (NZF). Acts as an
CC adapter linking MAP3K7/TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin
CC chains. The RanBP2-type zinc finger (NZF) specifically recognizes Lys-
CC 63'-linked polyubiquitin chains unanchored or anchored to the substrate
CC proteins such as RIPK1/RIP1: this acts as a scaffold to organize a
CC large signaling complex to promote autophosphorylation of MAP3K7/TAK1,
CC and subsequent activation of I-kappa-B-kinase (IKK) core complex by
CC MAP3K7/TAK1 (By similarity). Regulates the IL1-mediated translocation
CC of NCOR1 out of the nucleus (By similarity). Involved in heart
CC development (By similarity). {ECO:0000250|UniProtKB:Q99K90,
CC ECO:0000250|UniProtKB:Q9NYJ8}.
CC -!- SUBUNIT: Interacts with MAP3K7 and TRAF6. Identified in the TRIKA2
CC complex composed of MAP3K7, TAB1 and TAB2. Binds 'Lys-63'-linked
CC polyubiquitin chains (By similarity). Interacts with NCOR1 and HDAC3 to
CC form a ternary complex (By similarity). Interacts (via C-terminal) with
CC NUMBL (via PTB domain). Interacts (via the C-terminus) with DYNC2I2
CC (via WD domains). Interacts with RBCK1. Interacts with TRIM5 (By
CC similarity). Interacts with TRIM38 (via B30.2/SPRY domain), leading to
CC its translocation to lysosomes and degradation (By similarity).
CC {ECO:0000250|UniProtKB:Q99K90, ECO:0000250|UniProtKB:Q9NYJ8}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9NYJ8};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q9NYJ8}. Endosome
CC membrane {ECO:0000250|UniProtKB:Q9NYJ8}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9NYJ8}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q9NYJ8}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9NYJ8}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9NYJ8}. Note=Following IL1 stimulation,
CC translocation occurs from the membrane to cytosol. Interaction with
CC TRIM38 promotes translocation from cytosol to endosome and lysosome.
CC {ECO:0000250|UniProtKB:Q9NYJ8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5U303-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5U303-2; Sequence=VSP_017421;
CC -!- DOMAIN: The RanBP2-type zinc finger (NZF) mediates binding to two
CC consecutive 'Lys-63'-linked ubiquitins. {ECO:0000250|UniProtKB:Q9NYJ8}.
CC -!- PTM: Ubiquitinated; following IL1 stimulation or TRAF6 overexpression.
CC Ubiquitination involves RBCK1 leading to proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q9NYJ8}.
CC -!- PTM: Degraded in a lysosome-dependent manner following interactiuon
CC with TRIM38. {ECO:0000250|UniProtKB:Q9NYJ8}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:Q9NYJ8}.
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DR EMBL; BC085788; AAH85788.1; -; mRNA.
DR EMBL; CK364963; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001012062.1; NM_001012062.1. [Q5U303-2]
DR AlphaFoldDB; Q5U303; -.
DR BMRB; Q5U303; -.
DR SMR; Q5U303; -.
DR IntAct; Q5U303; 1.
DR STRING; 10116.ENSRNOP00000021904; -.
DR iPTMnet; Q5U303; -.
DR PhosphoSitePlus; Q5U303; -.
DR PaxDb; Q5U303; -.
DR PRIDE; Q5U303; -.
DR Ensembl; ENSRNOT00000021905; ENSRNOP00000021904; ENSRNOG00000016054. [Q5U303-1]
DR Ensembl; ENSRNOT00000061999; ENSRNOP00000058709; ENSRNOG00000016054. [Q5U303-2]
DR GeneID; 308267; -.
DR KEGG; rno:308267; -.
DR UCSC; RGD:1309527; rat. [Q5U303-1]
DR CTD; 23118; -.
DR RGD; 1309527; Tab2.
DR eggNOG; ENOG502QRAY; Eukaryota.
DR GeneTree; ENSGT00940000158473; -.
DR HOGENOM; CLU_025065_1_0_1; -.
DR InParanoid; Q5U303; -.
DR OMA; GPTFIHH; -.
DR OrthoDB; 324984at2759; -.
DR PhylomeDB; Q5U303; -.
DR TreeFam; TF332021; -.
DR Reactome; R-RNO-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-RNO-202424; Downstream TCR signaling.
DR Reactome; R-RNO-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-RNO-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-RNO-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
DR Reactome; R-RNO-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR Reactome; R-RNO-937042; IRAK2 mediated activation of TAK1 complex.
DR Reactome; R-RNO-9645460; Alpha-protein kinase 1 signaling pathway.
DR Reactome; R-RNO-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR PRO; PR:Q5U303; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016054; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; Q5U303; RN.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR CDD; cd14362; CUE_TAB2_TAB3; 1.
DR InterPro; IPR003892; CUE.
DR InterPro; IPR041911; TAB2/3_CUE.
DR InterPro; IPR001876; Znf_RanBP2.
DR InterPro; IPR036443; Znf_RanBP2_sf.
DR Pfam; PF02845; CUE; 1.
DR SMART; SM00546; CUE; 1.
DR SMART; SM00547; ZnF_RBZ; 1.
DR SUPFAM; SSF90209; SSF90209; 1.
DR PROSITE; PS51140; CUE; 1.
DR PROSITE; PS01358; ZF_RANBP2_1; 1.
DR PROSITE; PS50199; ZF_RANBP2_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Coiled coil; Cytoplasm; Endosome; Lysosome; Membrane;
KW Metal-binding; Methylation; Phosphoprotein; Reference proteome;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..693
FT /note="TGF-beta-activated kinase 1 and MAP3K7-binding
FT protein 2"
FT /id="PRO_0000225697"
FT DOMAIN 8..51
FT /note="CUE"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00468"
FT ZN_FING 663..693
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT REGION 90..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 224..310
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 564..583
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 640..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 675..685
FT /note="Interaction with polyubiquitin"
FT /evidence="ECO:0000250|UniProtKB:Q9NYJ8"
FT COILED 532..619
FT /evidence="ECO:0000255"
FT COMPBIAS 649..663
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 173
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYJ8"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYJ8"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYJ8"
FT MOD_RES 482
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYJ8"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYJ8"
FT MOD_RES 582
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NYJ8"
FT VAR_SEQ 621..693
FT /note="PHFNPSAIHNFYDNIGFVGPVPPKPKDQRSTIKAPKTQDTEDEEGAQWNCTA
FT CTFLNHPALIRCEQCEMPRHF -> KVQCILS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_017421"
SQ SEQUENCE 693 AA; 76328 MW; 2458318BAA02C0B4 CRC64;
MAQGSHQIDF QVLHDLRQKF PEVPEVVVSR CMLQNNNNLD ACCAVLSQES TRYLYGEGDL
NFSDESGISG LRNHMTSLNL DLQSQNVYHH GREGSRVNGS RTLTHSVSDG QLQGGQSNNE
LFQQEPQTAP AQVPQGFNVF GMPSTSGASN STPHLGFHLG SKGTSNLSQQ TPRFNPIMVT
LAPNIQTGRS TPTSLHIHGV PPPVLNSPQG NSIYIRPYIT TPSGAARQTQ QHSGWVSQFN
PVNPQQAYQP SQPGPWTTYP ASNPLPHTST QQPNQQGHQT SHVYMPISSP TTPQPPTVHS
SASSQSSAHS QYNIQNISTG PRKNQIEIKL EPPQRNSSSK LRSSGPRTAS TSSLVNSQTL
NRNQPTVYIA ASPPSTDEMI SRSQPKVYIS ANASTGDEQG MRNQPTLFIS TNSGASAASR
NMSGQVSMGP AFIHHHPPKS RVLGGNSAAS PRVVVTQPNT KYTFKITVSP NKPPAVSPGV
VSPTFELTNL LNHPDHYVET ETIQHLTDPT LAHVDRVSEA RKLSMGSDDA AYTQALLVHQ
KARMERLQRE LEMQKKKLDK LKSEVNEMEN SLTRRRLKRS NSMSQIPSLE EMQQLRSCNR
QLQIDIDCLT KEIDLFQARG PHFNPSAIHN FYDNIGFVGP VPPKPKDQRS TIKAPKTQDT
EDEEGAQWNC TACTFLNHPA LIRCEQCEMP RHF
