N4BP1_MOUSE
ID N4BP1_MOUSE Reviewed; 893 AA.
AC Q6A037; Q3TCI4; Q3UH87; Q3UY69;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 2.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=NEDD4-binding protein 1 {ECO:0000303|PubMed:11717310};
DE Short=N4BP1 {ECO:0000303|PubMed:11717310};
DE EC=3.1.-.- {ECO:0000250|UniProtKB:O75113};
GN Name=N4bp1 {ECO:0000303|PubMed:11717310, ECO:0000312|MGI:MGI:2136825};
GN Synonyms=Kiaa0615 {ECO:0000303|PubMed:15368895};
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 TISSUE=Pancreatic islet;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Olfactory bulb;
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 PARTIAL PROTEIN SEQUENCE, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ASP-488.
RX PubMed=32971525; DOI=10.1038/s41586-020-2796-5;
RA Gitlin A.D., Heger K., Schubert A.F., Reja R., Yan D., Pham V.C., Suto E.,
RA Zhang J., Kwon Y.C., Freund E.C., Kang J., Pham A., Caothien R.,
RA Bacarro N., Hinkle T., Xu M., McKenzie B.S., Haley B., Lee W.P., Lill J.R.,
RA Roose-Girma M., Dohse M., Webster J.D., Newton K., Dixit V.M.;
RT "Integration of innate immune signaling by caspase-8 cleavage of N4BP1.";
RL Nature 587:275-280(2020).
RN [4]
RP SUBCELLULAR LOCATION, UBIQUITINATION, AND INTERACTION WITH NEDD4.
RX PubMed=11717310; DOI=10.1074/jbc.m110047200;
RA Murillas R., Simms K.S., Hatakeyama S., Weissman A.M., Kuehn M.R.;
RT "Identification of developmentally expressed proteins that functionally
RT interact with Nedd4 ubiquitin ligase.";
RL J. Biol. Chem. 277:2897-2907(2002).
RN [5]
RP FUNCTION, AND INTERACTION WITH ITCH.
RX PubMed=17592138; DOI=10.1073/pnas.0701773104;
RA Oberst A., Malatesta M., Aqeilan R.I., Rossi M., Salomoni P., Murillas R.,
RA Sharma P., Kuehn M.R., Oren M., Croce C.M., Bernassola F., Melino G.;
RT "The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3
RT ligase Itch.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:11280-11285(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269; SER-299 AND SER-560, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, 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).
RN [7]
RP SUBCELLULAR LOCATION, UBIQUITINATION, SUMOYLATION, AND DESUMOYLATION BY
RP SENP1.
RX PubMed=20233849; DOI=10.1242/jcs.060160;
RA Sharma P., Murillas R., Zhang H., Kuehn M.R.;
RT "N4BP1 is a newly identified nucleolar protein that undergoes SUMO-
RT regulated polyubiquitylation and proteasomal turnover at promyelocytic
RT leukemia nuclear bodies.";
RL J. Cell Sci. 123:1227-1234(2010).
CC -!- FUNCTION: Potent suppressor of cytokine production that acts as a
CC regulator of innate immune signaling and inflammation
CC (PubMed:32971525). Acts as a key negative regulator of select cytokine
CC and chemokine responses elicited by TRIF-independent Toll-like
CC receptors (TLRs), thereby limiting inflammatory cytokine responses to
CC minor insults (PubMed:32971525). In response to more threatening
CC pathogens, cleaved by CASP8 downstream of TLR3 or TLR4, leading to its
CC inactivation, thereby allowing production of inflammatory cytokines
CC (PubMed:32971525). Acts as a restriction factor against some viruses:
CC restricts viral replication by binding to mRNA viruses and mediating
CC their degradation via its ribonuclease activity (By similarity). Also
CC acts as an inhibitor of the E3 ubiquitin-protein ligase ITCH: acts by
CC interacting with the second WW domain of ITCH, leading to compete with
CC ITCH's substrates and impairing ubiquitination of substrates
CC (PubMed:17592138). {ECO:0000250|UniProtKB:O75113,
CC ECO:0000269|PubMed:17592138, ECO:0000269|PubMed:32971525}.
CC -!- ACTIVITY REGULATION: Proteolytic cleavage by CASP8 or MALT1 leads to
CC its inactivation. {ECO:0000269|PubMed:32971525}.
CC -!- SUBUNIT: Interacts with NEDD4 (PubMed:11717310). Interacts with ITCH
CC (via WW domain 2) (PubMed:17592138). {ECO:0000269|PubMed:11717310,
CC ECO:0000269|PubMed:17592138}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:32971525}.
CC Nucleus {ECO:0000269|PubMed:11717310}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:20233849}. Nucleus, PML body
CC {ECO:0000269|PubMed:20233849}. Note=Primarily localizes to the
CC nucleolus (PubMed:20233849). Also localizes to the PML nuclear bodies,
CC when desumoylated (PubMed:20233849). {ECO:0000269|PubMed:20233849}.
CC -!- DOMAIN: The CoCUN region mediates binding to ubiquitin. Does not
CC interact with NEDD8. {ECO:0000250|UniProtKB:O75113}.
CC -!- PTM: Proteolytically cleaved by CASP8 downstream of TLR3 or TLR4,
CC leading to its inactivation (PubMed:32971525). Mainly cleaved at Asp-
CC 488 by CASP8 (PubMed:32971525). Cleaved by caspase-like protein MALT1,
CC leading to its inactivation (By similarity).
CC {ECO:0000250|UniProtKB:O75113, ECO:0000269|PubMed:32971525}.
CC -!- PTM: Mono- and polyubiquitinated on the CoCUN region (By similarity).
CC Monoubiquitinated by NEDD4 (PubMed:11717310). Polyubiquitinated,
CC leading to its degradation by the proteasome (PubMed:20233849).
CC Sumoylated with SUMO1, abrogating polyubiquitination and subsequent
CC degradation (PubMed:20233849). Desumoylated by SENP1, leading to
CC accumulation in PML nuclear bodies (PubMed:20233849).
CC {ECO:0000250|UniProtKB:O75113, ECO:0000269|PubMed:11717310,
CC ECO:0000269|PubMed:20233849}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable, fertile and grossly normal, but
CC develop mild, age-dependent inflammation and immune dysregulation.
CC {ECO:0000269|PubMed:32971525}.
CC -!- SIMILARITY: Belongs to the N4BP1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32259.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK172981; BAD32259.1; ALT_INIT; mRNA.
DR EMBL; AK134934; BAE22344.1; -; mRNA.
DR EMBL; AK147522; BAE27970.1; -; mRNA.
DR EMBL; AK170714; BAE41972.1; -; mRNA.
DR CCDS; CCDS52625.1; -.
DR RefSeq; NP_085040.2; NM_030563.2.
DR AlphaFoldDB; Q6A037; -.
DR SMR; Q6A037; -.
DR BioGRID; 219808; 3.
DR STRING; 10090.ENSMUSP00000034074; -.
DR iPTMnet; Q6A037; -.
DR PhosphoSitePlus; Q6A037; -.
DR EPD; Q6A037; -.
DR jPOST; Q6A037; -.
DR MaxQB; Q6A037; -.
DR PaxDb; Q6A037; -.
DR PeptideAtlas; Q6A037; -.
DR PRIDE; Q6A037; -.
DR ProteomicsDB; 252634; -.
DR Antibodypedia; 49389; 137 antibodies from 28 providers.
DR Ensembl; ENSMUST00000034074; ENSMUSP00000034074; ENSMUSG00000031652.
DR GeneID; 80750; -.
DR KEGG; mmu:80750; -.
DR UCSC; uc009mqo.2; mouse.
DR CTD; 9683; -.
DR MGI; MGI:2136825; N4bp1.
DR VEuPathDB; HostDB:ENSMUSG00000031652; -.
DR eggNOG; KOG3777; Eukaryota.
DR GeneTree; ENSGT00940000158682; -.
DR HOGENOM; CLU_014137_1_0_1; -.
DR InParanoid; Q6A037; -.
DR OMA; KIPYKLE; -.
DR OrthoDB; 771251at2759; -.
DR PhylomeDB; Q6A037; -.
DR TreeFam; TF315783; -.
DR BioGRID-ORCS; 80750; 7 hits in 74 CRISPR screens.
DR ChiTaRS; N4bp1; mouse.
DR PRO; PR:Q6A037; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q6A037; protein.
DR Bgee; ENSMUSG00000031652; Expressed in animal zygote and 244 other tissues.
DR Genevisible; Q6A037; MM.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:0004540; F:ribonuclease activity; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IMP:BHF-UCL.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:UniProtKB.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; IDA:UniProtKB.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR021869; RNase_Zc3h12_NYN.
DR Pfam; PF11977; RNase_Zc3h12a; 1.
DR SUPFAM; SSF54791; SSF54791; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Direct protein sequencing; Hydrolase; Immunity; Innate immunity;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome; RNA-binding;
KW Ubl conjugation.
FT CHAIN 1..893
FT /note="NEDD4-binding protein 1"
FT /id="PRO_0000301985"
FT DOMAIN 59..143
FT /note="KH-like"
FT /evidence="ECO:0000255"
FT DOMAIN 615..767
FT /note="RNase NYN"
FT /evidence="ECO:0000255"
FT REGION 213..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 273..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 472..564
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 793..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 846..893
FT /note="CoCUN"
FT /evidence="ECO:0000250|UniProtKB:O75113"
FT COMPBIAS 229..243
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 273..300
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..337
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..433
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 472..500
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 507..550
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 200..201
FT /note="Cleavage; by CASP8"
FT /evidence="ECO:0000269|PubMed:32971525"
FT SITE 325..326
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:32971525"
FT SITE 488..489
FT /note="Cleavage; by CASP8"
FT /evidence="ECO:0000269|PubMed:32971525"
FT SITE 507..508
FT /note="Cleavage; by MALT1"
FT /evidence="ECO:0000250|UniProtKB:O75113"
FT MOD_RES 241
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75113"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75113"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 560
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 488
FT /note="D->A: Prevents cleavage by CASP8 and subsequent
FT inactivation."
FT /evidence="ECO:0000269|PubMed:32971525"
FT CONFLICT 93
FT /note="G -> E (in Ref. 2; BAE27970)"
FT /evidence="ECO:0000305"
FT CONFLICT 671
FT /note="T -> P (in Ref. 2; BAE27970)"
FT /evidence="ECO:0000305"
FT CONFLICT 724
FT /note="R -> T (in Ref. 2; BAE27970)"
FT /evidence="ECO:0000305"
FT CONFLICT 733
FT /note="W -> C (in Ref. 2; BAE27970)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 893 AA; 99147 MW; AC6010E1F339B97A CRC64;
MAARVVLDEF TAPAEKAALL ERSRGRIEAL FGVGLAVLGA LGAEEPLPAR IWLQLRGAQE
AVHSAKEYIK GICEPELEEK ECYPKAMHCI FVGAQSLFLK SLIQDTCADL CVLDTGLLGI
RGSAEAVVMA RSHIQQFVKL FESNENLPSN QRESEIKREF RQFVEAHADS YTMDLLILPT
SLKKELLSLT QGEESLFETD DDVITVGDVR PPEYTQSAAT GPSSARDEVV VQEDSRNKAR
TPVSELTKHM DTVFSSSPDV LFVPVNGLSP DEDALSKDRV CHKRRSSDTE ERHTKKQFSL
ENVPEGELLP DGKGSAGNEV IDLSDPASNS TNLSPDGKDT TEEMEYNILV NFFKTMGYSQ
EIVEKVIREY GPSTEPLLLL EEIEKENKRL QEDRDFPPCT VYPDASQSRN AGVGSTTNEL
TADSTPKKAQ SHTEQSMVER FSQLPFKDSK HCTSNCKVNS FRTVPVGQKQ EIWGSKQNSS
CTVDLETDGH SASAASASPK DISFVSRGAS GHQQRNPAFP ENGFQQQTEP LLPNNTKPAC
EKRSGSCSSP QPKPNYPPLS PPLPLPQLLP SVTEARLGGS SDHIDSSVTG VQRFRDTLKI
PYKLELKNEP GRADLKHIVI DGSNVAITHG LKKFFSCRGI AIAVEYFWKL GNRNITVFVP
QWRTRRDPNI TEQHFLTQLQ ELGILSLTPA RMVFGERIAS HDDRFLLHLA DKTGGIIVTN
DNFREFVTES VSWREIITKR LLQYTFVGDI FMVPDDPLGR NGPRLEEFLR KEAFLRHMQP
LLNALPSVGT FDPGFRSPST QVANNSHQPP PRIQTSSSPW LPQQSHFTAL ATLPSMQQNP
PLPAQRSSAE TSELREALLK IFPDSEQKLK IDQILAAHPY MKDLNALSAL VLD
