ID TAB1_MOUSE Reviewed; 502 AA. AC Q8CF89; Q7TQJ5; Q80V65; Q8R0D1; DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot. DT 25-OCT-2005, sequence version 2. DT 27-MAR-2024, entry version 144. DE RecName: Full=TGF-beta-activated kinase 1 and MAP3K7-binding protein 1; DE AltName: Full=Mitogen-activated protein kinase kinase kinase 7-interacting protein 1; DE AltName: Full=TGF-beta-activated kinase 1-binding protein 1; DE Short=TAK1-binding protein 1; GN Name=Tab1; Synonyms=Map3k7ip1; 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], FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=12464436; DOI=10.1016/s0925-4773(02)00391-x; RA Komatsu Y., Shibuya H., Takeda N., Ninomiya-Tsuji J., Yasui T., Miyado K., RA Sekimoto T., Ueno N., Matsumoto K., Yamada G.; RT "Targeted disruption of the Tab1 gene causes embryonic lethality and RT defects in cardiovascular and lung morphogenesis."; RL Mech. Dev. 119:239-249(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Eye, Kidney, and 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Kidney, Lung, Pancreas, and Spleen; 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 [4] RP FUNCTION, AND UBIQUITNATION BY RNF114. RX PubMed=28073917; DOI=10.15252/embr.201642573; RA Yang Y., Zhou C., Wang Y., Liu W., Liu C., Wang L., Liu Y., Shang Y., RA Li M., Zhou S., Wang Y., Zeng W., Zhou J., Huo R., Li W.; RT "The E3 ubiquitin ligase RNF114 and TAB1 degradation are required for RT maternal-to-zygotic transition."; RL EMBO Rep. 18:205-216(2017). RN [5] RP FUNCTION, INTERACTION WITH STING1, AND SUBCELLULAR LOCATION. RX PubMed=37832545; DOI=10.1016/j.molcel.2023.09.009; RA Ma M., Dang Y., Chang B., Wang F., Xu J., Chen L., Su H., Li J., Ge B., RA Chen C., Liu H.; RT "TAK1 is an essential kinase for STING trafficking."; RL Mol. Cell 0:0-0(2023). RN [6] {ECO:0007744|PDB:4LOO, ECO:0007744|PDB:4LOP, ECO:0007744|PDB:4LOQ} RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 384-412, AND FUNCTION. RX PubMed=24037507; DOI=10.1038/nsmb.2668; RA DeNicola G.F., Martin E.D., Chaikuad A., Bassi R., Clark J., Martino L., RA Verma S., Sicard P., Tata R., Atkinson R.A., Knapp S., Conte M.R., RA Marber M.S.; RT "Mechanism and consequence of the autoactivation of p38alpha mitogen- RT activated protein kinase promoted by TAB1."; RL Nat. Struct. Mol. Biol. 20:1182-1190(2013). CC -!- FUNCTION: Key adapter protein that plays an essential role in JNK and CC NF-kappa-B activation and proinflammatory cytokines production in CC response to stimulation with TLRs and cytokines (PubMed:12464436, CC PubMed:28073917). Mechanistically, associates with the catalytic domain CC of MAP3K7/TAK1 to trigger MAP3K7/TAK1 autophosphorylation leading to CC its full activation (PubMed:37832545). Similarly, associates with CC MAPK14 and triggers its autophosphorylation and subsequent activation CC (PubMed:24037507). In turn, MAPK14 phosphorylates TAB1 and inhibits CC MAP3K7/TAK1 activation in a feedback control mechanism. Plays also a CC role in recruiting MAPK14 to the TAK1 complex for the phosphorylation CC of the TAB2 and TAB3 regulatory subunits (By similarity). CC {ECO:0000250|UniProtKB:Q15750, ECO:0000269|PubMed:12464436, CC ECO:0000269|PubMed:24037507, ECO:0000269|PubMed:28073917, CC ECO:0000269|PubMed:37832545}. CC -!- SUBUNIT: Interacts with XIAP and BIRC7 (By similarity). Interacts with CC TRAF6 and MAP3K7; during IL-1 signaling (By similarity). Identified in CC the TRIKA2 complex composed of MAP3K7, TAB1 and TAB2 (By similarity). CC Interacts with TRAF6 and MAPK14; these interactions allow MAPK14 CC autophosphorylation (By similarity). Interacts with STING1; interaction CC takes place following cGAMP activation and promotes TAB1 recruitment to CC the endoplasmic reticulum, triggering MAP3K7/TAK1 activation and STING1 CC phosphorylation (PubMed:37832545). {ECO:0000250|UniProtKB:Q15750, CC ECO:0000269|PubMed:37832545}. CC -!- INTERACTION: CC Q8CF89; P53349: Map3k1; NbExp=4; IntAct=EBI-1778503, EBI-447913; CC Q8CF89; Q62073: Map3k7; NbExp=2; IntAct=EBI-1778503, EBI-1775345; CC Q8CF89; Q86Y07-1: VRK2; Xeno; NbExp=2; IntAct=EBI-1778503, EBI-1207633; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:37832545}. CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:37832545}; CC Peripheral membrane protein {ECO:0000269|PubMed:37832545}; Cytoplasmic CC side {ECO:0000269|PubMed:37832545}. Note=Recruited to the endoplasmic CC reticulum following interaction with STING1. CC {ECO:0000269|PubMed:37832545}. CC -!- PTM: Phosphorylated at all three sites Ser-421, Thr-429 and Ser-436 by CC MAPK14 when cells were exposed to cellular stresses, or stimulated with CC TNF-alpha, IL1 or LPS. These phosphorylations inhibit TAK1 activation CC by a feedback control mechanism. Dephosphorylated by DUSP14 at Ser-436, CC leading to TAB1-MAP3K7/TAK1 complex inactivation in T-cells. CC {ECO:0000250|UniProtKB:Q15750}. CC -!- PTM: Ubiquitinated by MAP3K1 with 'Lys-63'-linked polyubiquitin; CC leading to activation of TAK1 and of JNK and p38 MAP kinases following CC EGF and TGF-beta stimulation. Ubiquitinated by ITCH with 'Lys-48'- CC linked polyubiquitin; leading to proteasomal degradation (By CC similarity). Ubiquitinated by RNF114 during maternal-to-zygotic CC transition; leading to degradation (PubMed:28073917). CC {ECO:0000250|UniProtKB:Q15750, ECO:0000269|PubMed:28073917}. CC -!- PTM: O-GlcNAcylated at Ser-393 is required for full MAP3K7/TAK1 CC activation upon stimulation with IL-1 or osmotic stress. CC {ECO:0000250|UniProtKB:Q15750}. CC -!- DISRUPTION PHENOTYPE: Mutant mice die in the late stages of gestation, CC exhibiting edema and severe embryonic hemorrhage. CC {ECO:0000269|PubMed:12464436}. CC -!- CAUTION: Lacks several key residues involved in metal-binding and CC catalytic activity, therefore has lost phosphatase activity. CC {ECO:0000250|UniProtKB:Q15750}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB088136; BAC43729.1; -; mRNA. DR EMBL; BC027054; AAH27054.1; -; mRNA. DR EMBL; BC041110; AAH41110.1; -; mRNA. DR EMBL; BC054369; AAH54369.1; -; mRNA. DR CCDS; CCDS27659.1; -. DR RefSeq; NP_079885.2; NM_025609.2. DR PDB; 4LOO; X-ray; 1.95 A; B=384-412. DR PDB; 4LOP; X-ray; 2.05 A; K/L/M/N=384-412. DR PDB; 4LOQ; X-ray; 2.32 A; K/L/M/N=384-412. DR PDBsum; 4LOO; -. DR PDBsum; 4LOP; -. DR PDBsum; 4LOQ; -. DR AlphaFoldDB; Q8CF89; -. DR SMR; Q8CF89; -. DR BioGRID; 211528; 13. DR ELM; Q8CF89; -. DR IntAct; Q8CF89; 12. DR MINT; Q8CF89; -. DR STRING; 10090.ENSMUSP00000023050; -. DR GlyGen; Q8CF89; 6 sites, 1 O-linked glycan (6 sites). DR iPTMnet; Q8CF89; -. DR PhosphoSitePlus; Q8CF89; -. DR EPD; Q8CF89; -. DR MaxQB; Q8CF89; -. DR PaxDb; 10090-ENSMUSP00000023050; -. DR PeptideAtlas; Q8CF89; -. DR ProteomicsDB; 253463; -. DR Pumba; Q8CF89; -. DR Antibodypedia; 12659; 723 antibodies from 44 providers. DR DNASU; 66513; -. DR Ensembl; ENSMUST00000023050.9; ENSMUSP00000023050.8; ENSMUSG00000022414.9. DR GeneID; 66513; -. DR KEGG; mmu:66513; -. DR UCSC; uc007wve.1; mouse. DR AGR; MGI:1913763; -. DR CTD; 10454; -. DR MGI; MGI:1913763; Tab1. DR VEuPathDB; HostDB:ENSMUSG00000022414; -. DR eggNOG; KOG0698; Eukaryota. DR GeneTree; ENSGT00510000048276; -. DR HOGENOM; CLU_027717_1_0_1; -. DR InParanoid; Q8CF89; -. DR OMA; CELSAGT; -. DR OrthoDB; 37076at2759; -. DR PhylomeDB; Q8CF89; -. DR TreeFam; TF317785; -. DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway. DR Reactome; R-MMU-2871837; FCERI mediated NF-kB activation. DR Reactome; R-MMU-445989; TAK1-dependent IKK and NF-kappa-B activation. DR Reactome; R-MMU-450302; activated TAK1 mediates p38 MAPK activation. DR Reactome; R-MMU-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. DR Reactome; R-MMU-5357956; TNFR1-induced NF-kappa-B signaling pathway. DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-MMU-5689880; Ub-specific processing proteases. DR Reactome; R-MMU-9020702; Interleukin-1 signaling. DR Reactome; R-MMU-937042; IRAK2 mediated activation of TAK1 complex. DR Reactome; R-MMU-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex. DR Reactome; R-MMU-9645460; Alpha-protein kinase 1 signaling pathway. DR Reactome; R-MMU-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation. DR BioGRID-ORCS; 66513; 15 hits in 79 CRISPR screens. DR ChiTaRS; Tab1; mouse. DR PRO; PR:Q8CF89; -. DR Proteomes; UP000000589; Chromosome 15. DR RNAct; Q8CF89; Protein. DR Bgee; ENSMUSG00000022414; Expressed in dorsal pancreas and 213 other cell types or tissues. DR ExpressionAtlas; Q8CF89; baseline and differential. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0016607; C:nuclear speck; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:0019209; F:kinase activator activity; IMP:MGI. DR GO; GO:0048273; F:mitogen-activated protein kinase p38 binding; ISO:MGI. DR GO; GO:0060090; F:molecular adaptor activity; IEA:Ensembl. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISS:UniProtKB. DR GO; GO:0004722; F:protein serine/threonine phosphatase activity; IEA:InterPro. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0035904; P:aorta development; IMP:MGI. DR GO; GO:0003279; P:cardiac septum development; IMP:MGI. DR GO; GO:0060976; P:coronary vasculature development; IMP:MGI. DR GO; GO:0003007; P:heart morphogenesis; IMP:MGI. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0030324; P:lung development; IMP:MGI. DR GO; GO:0038061; P:non-canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:MGI. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IMP:MGI. DR CDD; cd00143; PP2Cc; 1. DR Gene3D; 3.60.40.10; PPM-type phosphatase domain; 1. DR IDEAL; IID50233; -. DR InterPro; IPR015655; PP2C. DR InterPro; IPR036457; PPM-type-like_dom_sf. DR InterPro; IPR001932; PPM-type_phosphatase-like_dom. DR PANTHER; PTHR13832; PROTEIN PHOSPHATASE 2C; 1. DR PANTHER; PTHR13832:SF533; TGF-BETA-ACTIVATED KINASE 1 AND MAP3K7-BINDING PROTEIN 1; 1. DR Pfam; PF00481; PP2C; 1. DR SMART; SM00332; PP2Cc; 1. DR SUPFAM; SSF81606; PP2C-like; 1. DR PROSITE; PS51746; PPM_2; 1. DR Genevisible; Q8CF89; MM. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Endoplasmic reticulum; Glycoprotein; Membrane; KW Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..502 FT /note="TGF-beta-activated kinase 1 and MAP3K7-binding FT protein 1" FT /id="PRO_0000057798" FT DOMAIN 28..365 FT /note="PPM-type phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01082" FT REGION 1..21 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 414..476 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..20 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 414..460 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 482 FT /note="Required for interaction with MAP3K7" FT /evidence="ECO:0000250|UniProtKB:Q15750" FT MOD_RES 7 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 421 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15750" FT MOD_RES 429 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q15750" FT MOD_RES 436 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q15750" FT MOD_RES 440 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q15750" FT CARBOHYD 393 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000250|UniProtKB:Q15750" FT CONFLICT 199 FT /note="Q -> H (in Ref. 1; BAC43729)" FT /evidence="ECO:0000305" FT CONFLICT 210..212 FT /note="ENE -> DND (in Ref. 1; BAC43729)" FT /evidence="ECO:0000305" FT CONFLICT 323 FT /note="L -> P (in Ref. 1; BAC43729)" FT /evidence="ECO:0000305" SQ SEQUENCE 502 AA; 54616 MW; F7529D2E3CF30696 CRC64; MAAQRRSLLQ SEQQPSWTDD LPLCHLSGVG SASNRSYSAD GKGTESHPPE DNWLKFRSEN NCFLYGVFNG YDGNRVTNFV AQRLSAELLL GQLNTEHTEA DVRRVLLQAF DVVERSFLES IDDALAEKAS LQSQLPEGVP QHQLPPQYQK ILERLKALER EISGGAMAVV AVLLNSKLYV ANVGTNRALL CKSTVDGLQV TQLNMDHTTE NEDELFRLSQ LGLDAGKIKQ MGVICGQEST RRIGDYKVKY GYTDIDLLSA AKSKPIIAEP EIHGAQPLDG VTGFLVLMSE GLYKALEAAH GPGQANQEIA AMIDTEFAKQ TSLDAVAQAV VDRVKRIHSD TFASGGERAK FCPRHEDMTL LVRNFGYPLG EMSQPTPTPA PGGRVYPVSV PYSSAQSTSK TSVTLSLVMP SQGQMVNGSH SASTLDEATP TLTNQSPTLT LQSTNTHTQS SSSSSDGGLF RSRPAHSLPP GEDGRVEPYV DFAEFYRLWS VDHGEQSVMT AP //