INAVA_MOUSE
ID INAVA_MOUSE Reviewed; 663 AA.
AC Q7TN12; Q7TN27; Q8BGK3;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Innate immunity activator protein {ECO:0000250|UniProtKB:Q3KP66};
GN Name=Inava {ECO:0000250|UniProtKB:Q3KP66};
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].
RC STRAIN=C57BL/6J;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 564-663.
RC STRAIN=C57BL/6J; TISSUE=Testis;
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 [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29420262; DOI=10.1126/science.aan0814;
RA Mohanan V., Nakata T., Desch A.N., Levesque C., Boroughs A., Guzman G.,
RA Cao Z., Creasey E., Yao J., Boucher G., Charron G., Bhan A.K., Schenone M.,
RA Carr S.A., Reinecker H.C., Daly M.J., Rioux J.D., Lassen K.G., Xavier R.J.;
RT "C1orf106 is a colitis risk gene that regulates stability of epithelial
RT adherens junctions.";
RL Science 359:1161-1166(2018).
CC -!- FUNCTION: Expressed in peripheral macrophages and intestinal myeloid-
CC derived cells, is required for optimal PRR (pattern recognition
CC receptor)-induced signaling, cytokine secretion, and bacterial
CC clearance. Upon stimulation of a broad range of PRRs (pattern
CC recognition receptor) such as NOD2 or TLR2, TLR3, TLR4, TLR5, TLR7 and
CC TLR9, associates with YWHAQ/14-3-3T, which in turn leads to the
CC recruitment and activation of MAP kinases and NF-kappa-B signaling
CC complexes that amplifies PRR-induced downstream signals and cytokine
CC secretion (By similarity). In the intestine, regulates adherens
CC junction stability by regulating the degradation of CYTH1 and CYTH2,
CC probably acting as substrate cofactor for SCF E3 ubiquitin-protein
CC ligase complexes. Stabilizes adherens junctions by limiting CYTH1-
CC dependent ARF6 activation (PubMed:29420262).
CC {ECO:0000250|UniProtKB:Q3KP66, ECO:0000269|PubMed:29420262}.
CC -!- SUBUNIT: Interacts with IRAK1, NOD2 and RIPK2; the interaction takes
CC place upon PRR stimulation. Interacts with YWHAQ/14-3-3T; the
CC interaction increases upon PRR stimulation and is required for cellular
CC signaling pathway activation and cytokine secretion. Interacts (via N-
CC terminal domain) with CYTH1 and CYTH2 (via their N-terminal domains).
CC Interacts with FBXW11 and BTRC; associates with SCF E3 ubiquitin-
CC protein ligase complexes (By similarity).
CC {ECO:0000250|UniProtKB:Q3KP66}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q3KP66}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q3KP66}. Note=Translocates to the nucleus upon
CC NOD2 stimulation. {ECO:0000250|UniProtKB:Q3KP66}.
CC -!- DISRUPTION PHENOTYPE: After infection with Citrobacter rodentium,
CC mutants show significantly increased bacterial loads at day 5 compared
CC to wild-types. They are able to control the infection by day 12 post-
CC infection, they exhibit significantly shortened colon length. They
CC don't have impaired cytokine response (PubMed:29420262). Mutants also
CC exhibit impaired recovery from dextran sodium sulfate-induces colitis,
CC they show increased body weight loss and reduced colon length
CC (PubMed:29420262). {ECO:0000269|PubMed:29420262}.
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DR EMBL; BC052416; AAH52416.2; -; mRNA.
DR EMBL; BC053100; AAH53100.1; -; mRNA.
DR EMBL; AK006603; BAC25149.1; -; mRNA.
DR EMBL; AK018917; BAC25571.1; -; mRNA.
DR RefSeq; NP_083148.3; NM_028872.3.
DR AlphaFoldDB; Q7TN12; -.
DR SMR; Q7TN12; -.
DR STRING; 10090.ENSMUSP00000113785; -.
DR iPTMnet; Q7TN12; -.
DR PhosphoSitePlus; Q7TN12; -.
DR MaxQB; Q7TN12; -.
DR PaxDb; Q7TN12; -.
DR PRIDE; Q7TN12; -.
DR ProteomicsDB; 266989; -.
DR DNASU; 67313; -.
DR GeneID; 67313; -.
DR KEGG; mmu:67313; -.
DR CTD; 55765; -.
DR MGI; MGI:1921579; Inava.
DR eggNOG; KOG3529; Eukaryota.
DR InParanoid; Q7TN12; -.
DR OrthoDB; 509744at2759; -.
DR PhylomeDB; Q7TN12; -.
DR BioGRID-ORCS; 67313; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Inava; mouse.
DR PRO; PR:Q7TN12; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q7TN12; protein.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0034334; P:adherens junction maintenance; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0060729; P:intestinal epithelial structure maintenance; IMP:UniProtKB.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0002221; P:pattern recognition receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; ISS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; ISS:UniProtKB.
DR GO; GO:1903409; P:reactive oxygen species biosynthetic process; ISS:UniProtKB.
DR GO; GO:0032495; P:response to muramyl dipeptide; ISS:UniProtKB.
DR GO; GO:0032494; P:response to peptidoglycan; ISS:UniProtKB.
DR InterPro; IPR043447; CCDC120/INAVA.
DR InterPro; IPR021774; DUF3338.
DR InterPro; IPR039106; INAVA.
DR PANTHER; PTHR16093; PTHR16093; 1.
DR PANTHER; PTHR16093:SF4; PTHR16093:SF4; 1.
DR Pfam; PF11819; CUPID; 1.
PE 2: Evidence at transcript level;
KW Coiled coil; Cytoplasm; Immunity; Innate immunity; Nucleus;
KW Reference proteome.
FT CHAIN 1..663
FT /note="Innate immunity activator protein"
FT /id="PRO_0000251730"
FT REGION 1..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 219..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 375..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 448..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 117..147
FT /evidence="ECO:0000255"
FT MOTIF 164..170
FT /note="Nuclear localization signal (NLS) 1"
FT /evidence="ECO:0000250|UniProtKB:Q3KP66"
FT MOTIF 332..338
FT /note="Nuclear localization signal (NLS) 2"
FT /evidence="ECO:0000250|UniProtKB:Q3KP66"
FT MOTIF 422..428
FT /note="Nuclear localization signal (NLS) 3"
FT /evidence="ECO:0000250|UniProtKB:Q3KP66"
FT COMPBIAS 219..244
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 248..268
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..299
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 342..363
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 380..405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 455..476
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 564
FT /note="R -> G (in Ref. 2; BAC25149/BAC25571)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 663 AA; 72693 MW; 3B1BEB1A8D6298E1 CRC64;
MLQMPKLNEI PPGRGGPGEP WGEGRWAGPT GPEAARPARG ARGQARGARA RWDSWEHSRL
PTHPGPGWDQ CSPSFLCAPS SQKLIMESKD EVSDSDSGII LQSGPDSPVS PMKELTNAVR
KQQRALEARL EACLEELRRL CLREAELTGT LPAEYPLKPG EKAPKVRRRI GAAYKLDEWA
LHREDPLSSL ERQLALQLQI TEAARRLCAE ENLSRQARRQ RKHAALQEEK KLRDLQRCLG
DRRRNSEPPP TTVPSLGREL SASDDSSLSD GLLLEEEDSQ APKPPPESPA PPSRPLPPQS
LEGLQPTGPE SGGQERAPIQ NSPWKETSLD HPYEKPRKSS ELSSESSSPA TTPQDQPNPS
SLWVLDAASY HVVPIRNVPG QRQGRTSAPA TPEMQGRRGQ SQSLRVDSFR AGAEGRGRSA
FPRRRPTHYT VTVPDSCFTP GKPPLPHPAC HSCSEDSGSD VSSISHPTSP GSSSPDISFL
RPLCLPEPPR HRGAWGPACG RELAPHYSKL LLPAGYFPTG RYVMVAEGHL PPGEWELCRA
AVGAAYDEEG APLRYQRLVP SHSRIVRTPS LKDSPAGRGL SKAAVSEELK WWHERARLRS
SRPHSLDRQG AFRVRSLPPG RESFGRASGP RTQVPPVYVL RRSTDGAPVQ VFVPENGEII
SQV
