KBRS1_HUMAN
ID KBRS1_HUMAN Reviewed; 192 AA.
AC Q9NYS0; Q96K18;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=NF-kappa-B inhibitor-interacting Ras-like protein 1;
DE AltName: Full=I-kappa-B-interacting Ras-like protein 1;
DE Short=Kappa B-Ras protein 1;
DE Short=KappaB-Ras1;
GN Name=NKIRAS1; Synonyms=KBRAS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, GTP-BINDING, AND
RP INTERACTION WITH NFKBIA AND NFKBIB.
RX PubMed=10657303; DOI=10.1126/science.287.5454.869;
RA Fenwick C., Na S.-Y., Voll R.E., Zhong H., Im S.-Y., Lee J.W., Ghosh S.;
RT "A subclass of Ras proteins that regulate the degradation of IkappaB.";
RL Science 287:869-873(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Lung;
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 [5]
RP FUNCTION, AND INTERACTION WITH NFKBIB.
RX PubMed=12672800; DOI=10.1074/jbc.m301021200;
RA Chen Y., Wu J., Ghosh G.;
RT "KappaB-Ras binds to the unique insert within the ankyrin repeat domain of
RT IkappaBbeta and regulates cytoplasmic retention of IkappaBbeta.NF-kappaB
RT complexes.";
RL J. Biol. Chem. 278:23101-23106(2003).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH REL, AND MUTAGENESIS OF
RP THR-38.
RX PubMed=15024091; DOI=10.1128/mcb.24.7.3048-3056.2004;
RA Chen Y., Vallee S., Wu J., Vu D., Sondek J., Ghosh G.;
RT "Inhibition of NF-kappaB activity by IkappaBbeta in association with
RT kappaB-Ras.";
RL Mol. Cell. Biol. 24:3048-3056(2004).
CC -!- FUNCTION: Atypical Ras-like protein that acts as a potent regulator of
CC NF-kappa-B activity by preventing the degradation of NF-kappa-B
CC inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more
CC resistant to degradation. May act by blocking phosphorylation of NFKBIB
CC and mediating cytoplasmic retention of p65/RELA NF-kappa-B subunit. It
CC is unclear whether it acts as a GTPase. Both GTP- and GDP-bound forms
CC block phosphorylation of NFKBIB. {ECO:0000269|PubMed:10657303,
CC ECO:0000269|PubMed:12672800, ECO:0000269|PubMed:15024091}.
CC -!- SUBUNIT: Interacts with both NF-kappa-B inhibitor alpha (NFKBIA) and
CC beta (NFKBIB) in vitro. However, it probably only interacts with NFKBIB
CC in vivo. Forms a complex with NFKBIB and NF-kappa-B heterodimer
CC (p50/NFKB1 and p65/RELA). Also interacts with c-Rel (REL).
CC {ECO:0000269|PubMed:10657303, ECO:0000269|PubMed:12672800,
CC ECO:0000269|PubMed:15024091}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15024091}.
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10657303}.
CC -!- DOMAIN: In contrast to other members of the Ras family, the members of
CC the KappaB-Ras subfamily do not contain the conserved Gly and Gln
CC residues in positions 13 and 65, which are replaced by Leu residues,
CC and are therefore similar to the constitutively active forms of
CC oncogenic forms of Ras. This suggests that members of this family are
CC clearly different from other small GTPases proteins.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC KappaB-Ras subfamily. {ECO:0000305}.
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DR EMBL; AF229839; AAF34998.1; -; mRNA.
DR EMBL; AK027749; BAB55341.1; -; mRNA.
DR EMBL; DQ314881; ABC40740.1; -; Genomic_DNA.
DR EMBL; BC066940; AAH66940.1; -; mRNA.
DR EMBL; BC012145; AAH12145.1; -; mRNA.
DR CCDS; CCDS33717.1; -.
DR RefSeq; NP_065078.1; NM_020345.3.
DR RefSeq; XP_005265133.1; XM_005265076.3.
DR RefSeq; XP_005265134.1; XM_005265077.4.
DR RefSeq; XP_005265135.1; XM_005265078.3.
DR AlphaFoldDB; Q9NYS0; -.
DR SMR; Q9NYS0; -.
DR BioGRID; 118389; 16.
DR IntAct; Q9NYS0; 5.
DR STRING; 9606.ENSP00000393785; -.
DR iPTMnet; Q9NYS0; -.
DR PhosphoSitePlus; Q9NYS0; -.
DR BioMuta; NKIRAS1; -.
DR DMDM; 74753075; -.
DR EPD; Q9NYS0; -.
DR jPOST; Q9NYS0; -.
DR MassIVE; Q9NYS0; -.
DR MaxQB; Q9NYS0; -.
DR PaxDb; Q9NYS0; -.
DR PeptideAtlas; Q9NYS0; -.
DR PRIDE; Q9NYS0; -.
DR ProteomicsDB; 83272; -.
DR Antibodypedia; 11367; 365 antibodies from 32 providers.
DR DNASU; 28512; -.
DR Ensembl; ENST00000388759.7; ENSP00000373411.3; ENSG00000197885.11.
DR Ensembl; ENST00000416026.2; ENSP00000394214.2; ENSG00000197885.11.
DR Ensembl; ENST00000421515.6; ENSP00000392307.2; ENSG00000197885.11.
DR Ensembl; ENST00000425478.7; ENSP00000400385.2; ENSG00000197885.11.
DR Ensembl; ENST00000443659.6; ENSP00000393785.2; ENSG00000197885.11.
DR Ensembl; ENST00000614374.4; ENSP00000483749.1; ENSG00000197885.11.
DR GeneID; 28512; -.
DR KEGG; hsa:28512; -.
DR MANE-Select; ENST00000425478.7; ENSP00000400385.2; NM_020345.4; NP_065078.1.
DR UCSC; uc003ccj.4; human.
DR CTD; 28512; -.
DR DisGeNET; 28512; -.
DR GeneCards; NKIRAS1; -.
DR HGNC; HGNC:17899; NKIRAS1.
DR HPA; ENSG00000197885; Low tissue specificity.
DR MalaCards; NKIRAS1; -.
DR MIM; 604496; gene.
DR neXtProt; NX_Q9NYS0; -.
DR OpenTargets; ENSG00000197885; -.
DR PharmGKB; PA134958823; -.
DR VEuPathDB; HostDB:ENSG00000197885; -.
DR eggNOG; KOG3883; Eukaryota.
DR GeneTree; ENSGT00940000159705; -.
DR HOGENOM; CLU_041217_17_0_1; -.
DR InParanoid; Q9NYS0; -.
DR OMA; ADMAQQW; -.
DR OrthoDB; 1382000at2759; -.
DR PhylomeDB; Q9NYS0; -.
DR TreeFam; TF314483; -.
DR PathwayCommons; Q9NYS0; -.
DR Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR SignaLink; Q9NYS0; -.
DR BioGRID-ORCS; 28512; 15 hits in 1075 CRISPR screens.
DR ChiTaRS; NKIRAS1; human.
DR GenomeRNAi; 28512; -.
DR Pharos; Q9NYS0; Tbio.
DR PRO; PR:Q9NYS0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NYS0; protein.
DR Bgee; ENSG00000197885; Expressed in lateral nuclear group of thalamus and 197 other tissues.
DR ExpressionAtlas; Q9NYS0; baseline and differential.
DR Genevisible; Q9NYS0; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0032794; F:GTPase activating protein binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; NAS:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; NAS:UniProtKB.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0032484; P:Ral protein signal transduction; IBA:GO_Central.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0043129; P:surfactant homeostasis; IBA:GO_Central.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR042227; KBRS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR PANTHER; PTHR46152; PTHR46152; 1.
DR Pfam; PF00071; Ras; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; GTP-binding; Nucleotide-binding; Reference proteome.
FT CHAIN 1..192
FT /note="NF-kappa-B inhibitor-interacting Ras-like protein 1"
FT /id="PRO_0000225675"
FT REGION 58..93
FT /note="Interactions with NFKBIA and NFKBIB"
FT REGION 168..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 35..43
FT /note="Effector region"
FT BINDING 11..18
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 61..65
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 120..123
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MUTAGEN 38
FT /note="T->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:15024091"
FT CONFLICT 95
FT /note="Q -> R (in Ref. 2; BAB55341)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 192 AA; 21643 MW; 84948448BE0853B0 CRC64;
MGKGCKVVVC GLLSVGKTAI LEQLLYGNHT IGMEDCETME DVYMASVETD RGVKEQLHLY
DTRGLQEGVE LPKHYFSFAD GFVLVYSVNN LESFQRVELL KKEIDKFKDK KEVAIVVLGN
KIDLSEQRQV DAEVAQQWAK SEKVRLWEVT VTDRKTLIEP FTLLASKLSQ PQSKSSFPLP
GRKNKGNSNS EN
