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   27-MAR-2024, entry version 166.
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}.
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; 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; 9606-ENSP00000393785; -.
DR   PeptideAtlas; Q9NYS0; -.
DR   ProteomicsDB; 83272; -.
DR   Pumba; Q9NYS0; -.
DR   Antibodypedia; 11367; 397 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   AGR; HGNC:17899; -.
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; 2882700at2759; -.
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 1152 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 198 other cell types or tissues.
DR   ExpressionAtlas; Q9NYS0; baseline and differential.
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:canonical NF-kappaB signal transduction; IEA:InterPro.
DR   GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR   GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; NAS:UniProtKB.
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; IEA:Ensembl.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR042227; KBRS.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR005225; Small_GTP-bd_dom.
DR   InterPro; IPR001806; Small_GTPase.
DR   NCBIfam; TIGR00231; small_GTP; 1.
DR   PANTHER; PTHR46152; NF-KAPPA-B INHIBITOR-INTERACTING RAS-LIKE PROTEIN; 1.
DR   PANTHER; PTHR46152:SF1; NF-KAPPA-B INHIBITOR-INTERACTING RAS-LIKE PROTEIN 1; 1.
DR   Pfam; PF00071; Ras; 1.
DR   PRINTS; PR00449; RASTRNSFRMNG.
DR   SMART; SM00175; RAB; 1.
DR   SMART; SM00173; RAS; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS51419; RAB; 1.
DR   Genevisible; Q9NYS0; HS.
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
//