KBRS2_HUMAN
ID KBRS2_HUMAN Reviewed; 191 AA.
AC Q9NYR9; A6NCZ5; B3KNN0; B4DNM3; Q6PK52; Q96KC7; Q9NSX1;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=NF-kappa-B inhibitor-interacting Ras-like protein 2;
DE AltName: Full=I-kappa-B-interacting Ras-like protein 2;
DE Short=Kappa B-Ras protein 2;
DE Short=KappaB-Ras2;
GN Name=NKIRAS2; Synonyms=KBRAS2;
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] (ISOFORM 1), TISSUE SPECIFICITY, AND INTERACTION
RP 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] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Embryo, and Thymus;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Muscle;
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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
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 nuclear localization of p65/RELA NF-kappa-B subunit. It is unclear
CC whether it acts as a GTPase. Both GTP- and GDP-bound forms block
CC phosphorylation of NFKBIB (By similarity). {ECO:0000250}.
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. {ECO:0000269|PubMed:10657303}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q9NYR9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NYR9-2; Sequence=VSP_017412;
CC Name=3;
CC IsoId=Q9NYR9-3; Sequence=VSP_043151;
CC Name=4;
CC IsoId=Q9NYR9-4; Sequence=VSP_044873, VSP_044874;
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 Ala and Leu
CC residues, respectively, and are therefore similar to the constitutively
CC active forms of oncogenic forms of Ras. This suggests that members of
CC this family are clearly different from other small GTPases proteins.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family.
CC KappaB-Ras subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB55006.1; Type=Miscellaneous discrepancy; Note=Absence of residues from position 133 within an exon that change the frame which is not the result of an alternative splicing.; Evidence={ECO:0000305};
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DR EMBL; AF229840; AAF34999.1; -; mRNA.
DR EMBL; AK027265; BAB55006.1; ALT_SEQ; mRNA.
DR EMBL; AK054571; BAG51392.1; -; mRNA.
DR EMBL; AK297975; BAG60285.1; -; mRNA.
DR EMBL; DB126967; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL137682; CAB70873.2; -; mRNA.
DR EMBL; DQ314882; ABC40741.1; -; Genomic_DNA.
DR EMBL; AC105024; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471152; EAW60791.1; -; Genomic_DNA.
DR EMBL; BC007450; AAH07450.1; -; mRNA.
DR EMBL; BC063498; AAH63498.1; -; mRNA.
DR CCDS; CCDS11415.1; -. [Q9NYR9-1]
DR CCDS; CCDS45679.1; -. [Q9NYR9-3]
DR CCDS; CCDS45680.1; -. [Q9NYR9-4]
DR PIR; T46440; T46440.
DR RefSeq; NP_001001349.1; NM_001001349.2. [Q9NYR9-1]
DR RefSeq; NP_001138399.1; NM_001144927.1. [Q9NYR9-1]
DR RefSeq; NP_001138400.1; NM_001144928.1. [Q9NYR9-3]
DR RefSeq; NP_001138401.1; NM_001144929.1. [Q9NYR9-4]
DR RefSeq; NP_060065.2; NM_017595.5. [Q9NYR9-1]
DR RefSeq; XP_005257308.1; XM_005257251.1. [Q9NYR9-1]
DR AlphaFoldDB; Q9NYR9; -.
DR SMR; Q9NYR9; -.
DR BioGRID; 118388; 24.
DR IntAct; Q9NYR9; 14.
DR MINT; Q9NYR9; -.
DR STRING; 9606.ENSP00000303580; -.
DR iPTMnet; Q9NYR9; -.
DR PhosphoSitePlus; Q9NYR9; -.
DR BioMuta; NKIRAS2; -.
DR DMDM; 74734716; -.
DR EPD; Q9NYR9; -.
DR jPOST; Q9NYR9; -.
DR MassIVE; Q9NYR9; -.
DR MaxQB; Q9NYR9; -.
DR PaxDb; Q9NYR9; -.
DR PeptideAtlas; Q9NYR9; -.
DR PRIDE; Q9NYR9; -.
DR ProteomicsDB; 83269; -. [Q9NYR9-1]
DR ProteomicsDB; 83270; -. [Q9NYR9-2]
DR ProteomicsDB; 83271; -. [Q9NYR9-3]
DR Antibodypedia; 79897; 219 antibodies from 31 providers.
DR DNASU; 28511; -.
DR Ensembl; ENST00000307641.9; ENSP00000303580.5; ENSG00000168256.18. [Q9NYR9-1]
DR Ensembl; ENST00000393880.5; ENSP00000377458.1; ENSG00000168256.18. [Q9NYR9-1]
DR Ensembl; ENST00000393881.7; ENSP00000377459.3; ENSG00000168256.18. [Q9NYR9-1]
DR Ensembl; ENST00000393885.9; ENSP00000377463.3; ENSG00000168256.18. [Q9NYR9-1]
DR Ensembl; ENST00000449471.8; ENSP00000401976.4; ENSG00000168256.18. [Q9NYR9-3]
DR Ensembl; ENST00000479407.5; ENSP00000465633.1; ENSG00000168256.18. [Q9NYR9-4]
DR GeneID; 28511; -.
DR KEGG; hsa:28511; -.
DR MANE-Select; ENST00000393885.9; ENSP00000377463.3; NM_017595.6; NP_060065.2.
DR UCSC; uc002hyq.4; human. [Q9NYR9-1]
DR CTD; 28511; -.
DR DisGeNET; 28511; -.
DR GeneCards; NKIRAS2; -.
DR HGNC; HGNC:17898; NKIRAS2.
DR HPA; ENSG00000168256; Low tissue specificity.
DR MIM; 604497; gene.
DR neXtProt; NX_Q9NYR9; -.
DR OpenTargets; ENSG00000168256; -.
DR PharmGKB; PA134968907; -.
DR VEuPathDB; HostDB:ENSG00000168256; -.
DR eggNOG; KOG3883; Eukaryota.
DR GeneTree; ENSGT00940000157943; -.
DR HOGENOM; CLU_041217_17_1_1; -.
DR InParanoid; Q9NYR9; -.
DR OMA; HPPQTKS; -.
DR PhylomeDB; Q9NYR9; -.
DR TreeFam; TF314483; -.
DR PathwayCommons; Q9NYR9; -.
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; Q9NYR9; -.
DR BioGRID-ORCS; 28511; 13 hits in 1079 CRISPR screens.
DR ChiTaRS; NKIRAS2; human.
DR GeneWiki; NKIRAS2; -.
DR GenomeRNAi; 28511; -.
DR Pharos; Q9NYR9; Tbio.
DR PRO; PR:Q9NYR9; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9NYR9; protein.
DR Bgee; ENSG00000168256; Expressed in cortical plate and 204 other tissues.
DR ExpressionAtlas; Q9NYR9; baseline and differential.
DR Genevisible; Q9NYR9; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0006954; P:inflammatory response; IEA:Ensembl.
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:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
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 Alternative splicing; Cytoplasm; GTP-binding; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..191
FT /note="NF-kappa-B inhibitor-interacting Ras-like protein 2"
FT /id="PRO_0000225679"
FT REGION 1..191
FT /note="Small GTPase-like"
FT REGION 169..191
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 VAR_SEQ 33..34
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017412"
FT VAR_SEQ 57..112
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043151"
FT VAR_SEQ 57..97
FT /note="VRFYDTRGLRDGAELPRHCFSCTDGYVLVYSTDSRESFQRV -> IAESLFS
FT VWSCSRRRLTNPRTRRRSPSWSLATSVTYRSSGV (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044873"
FT VAR_SEQ 98..191
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044874"
SQ SEQUENCE 191 AA; 21508 MW; 27429230DA563342 CRC64;
MGKSCKVVVC GQASVGKTSI LEQLLYGNHV VGSEMIETQE DIYVGSIETD RGVREQVRFY
DTRGLRDGAE LPRHCFSCTD GYVLVYSTDS RESFQRVELL KKEIDKSKDK KEVTIVVLGN
KCDLQEQRRV DPDVAQHWAK SEKVKLWEVS VADRRSLLEP FVYLASKMTQ PQSKSAFPLS
RKNKGSGSLD G
