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Protein

NF-kappa-B inhibitor-interacting Ras-like protein 2

Gene

NKIRAS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation. May act by blocking phosphorylation of NFKBIB and nuclear localization of p65/RELA NF-kappa-B subunit. It is unclear whether it acts as a GTPase. Both GTP- and GDP-bound forms block phosphorylation of NFKBIB (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi11 – 188GTPBy similarity
Nucleotide bindingi61 – 655GTPBy similarity
Nucleotide bindingi120 – 1234GTPBy similarity

GO - Molecular functioni

  1. GTPase activity Source: UniProtKB
  2. GTP binding Source: UniProtKB-KW

GO - Biological processi

  1. I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  2. metabolic process Source: GOC
  3. small GTPase mediated signal transduction Source: InterPro
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
NF-kappa-B inhibitor-interacting Ras-like protein 2
Alternative name(s):
I-kappa-B-interacting Ras-like protein 2
Short name:
Kappa B-Ras protein 2
Short name:
KappaB-Ras2
Gene namesi
Name:NKIRAS2
Synonyms:KBRAS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:17898. NKIRAS2.

Subcellular locationi

  1. Cytoplasm By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134968907.

Polymorphism and mutation databases

BioMutaiNKIRAS2.
DMDMi74734716.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 191191NF-kappa-B inhibitor-interacting Ras-like protein 2PRO_0000225679Add
BLAST

Proteomic databases

MaxQBiQ9NYR9.
PaxDbiQ9NYR9.
PRIDEiQ9NYR9.

PTM databases

PhosphoSiteiQ9NYR9.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiQ9NYR9.
CleanExiHS_NKIRAS2.
ExpressionAtlasiQ9NYR9. baseline and differential.
GenevestigatoriQ9NYR9.

Interactioni

Subunit structurei

Interacts with both NF-kappa-B inhibitor alpha (NFKBIA) and beta (NFKBIB) in vitro. However, it probably only interacts with NFKBIB in vivo.1 Publication

Protein-protein interaction databases

BioGridi118388. 6 interactions.
IntActiQ9NYR9. 3 interactions.
MINTiMINT-6945136.
STRINGi9606.ENSP00000303580.

Structurei

3D structure databases

ProteinModelPortaliQ9NYR9.
SMRiQ9NYR9. Positions 6-155.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 191191Small GTPase-likeAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi35 – 439Effector region

Domaini

In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by Ala and Leu residues, respectively, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins.

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG302793.
GeneTreeiENSGT00390000006495.
HOGENOMiHOG000230991.
HOVERGENiHBG105089.
InParanoidiQ9NYR9.
KOiK17197.
PhylomeDBiQ9NYR9.
TreeFamiTF314483.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51419. RAB. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NYR9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGKSCKVVVC GQASVGKTSI LEQLLYGNHV VGSEMIETQE DIYVGSIETD
60 70 80 90 100
RGVREQVRFY DTRGLRDGAE LPRHCFSCTD GYVLVYSTDS RESFQRVELL
110 120 130 140 150
KKEIDKSKDK KEVTIVVLGN KCDLQEQRRV DPDVAQHWAK SEKVKLWEVS
160 170 180 190
VADRRSLLEP FVYLASKMTQ PQSKSAFPLS RKNKGSGSLD G
Length:191
Mass (Da):21,508
Last modified:October 1, 2000 - v1
Checksum:i27429230DA563342
GO
Isoform 2 (identifier: Q9NYR9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     33-34: Missing.

Note: No experimental confirmation available.

Show »
Length:189
Mass (Da):21,292
Checksum:i4857EEA02F788F38
GO
Isoform 3 (identifier: Q9NYR9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     57-112: Missing.

Note: No experimental confirmation available.

Show »
Length:135
Mass (Da):14,910
Checksum:i8B874EC8C7EF28E4
GO
Isoform 4 (identifier: Q9NYR9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     57-97: VRFYDTRGLR...TDSRESFQRV → IAESLFSVWS...TSVTYRSSGV
     98-191: Missing.

Note: No experimental confirmation available.

Show »
Length:97
Mass (Da):10,770
Checksum:i4049375BE44AF8A5
GO

Sequence cautioni

The sequence BAB55006.1 differs from that shown.Absence of residues from position 133 within an exon that change the frame which is not the result of an alternative splicing.Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei33 – 342Missing in isoform 2. 1 PublicationVSP_017412
Alternative sequencei57 – 11256Missing in isoform 3. 1 PublicationVSP_043151Add
BLAST
Alternative sequencei57 – 9741VRFYD…SFQRV → IAESLFSVWSCSRRRLTNPR TRRRSPSWSLATSVTYRSSG V in isoform 4. 1 PublicationVSP_044873Add
BLAST
Alternative sequencei98 – 19194Missing in isoform 4. 1 PublicationVSP_044874Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF229840 mRNA. Translation: AAF34999.1.
AK027265 mRNA. Translation: BAB55006.1. Sequence problems.
AK054571 mRNA. Translation: BAG51392.1.
AK297975 mRNA. Translation: BAG60285.1.
DB126967 mRNA. No translation available.
AL137682 mRNA. Translation: CAB70873.2.
DQ314882 Genomic DNA. Translation: ABC40741.1.
AC105024 Genomic DNA. No translation available.
CH471152 Genomic DNA. Translation: EAW60791.1.
BC007450 mRNA. Translation: AAH07450.1.
BC063498 mRNA. Translation: AAH63498.1.
CCDSiCCDS11415.1. [Q9NYR9-1]
CCDS45679.1. [Q9NYR9-3]
CCDS45680.1. [Q9NYR9-4]
PIRiT46440.
RefSeqiNP_001001349.1. NM_001001349.2. [Q9NYR9-1]
NP_001138399.1. NM_001144927.1. [Q9NYR9-1]
NP_001138400.1. NM_001144928.1. [Q9NYR9-3]
NP_001138401.1. NM_001144929.1. [Q9NYR9-4]
NP_060065.2. NM_017595.5. [Q9NYR9-1]
XP_005257308.1. XM_005257251.1. [Q9NYR9-1]
UniGeneiHs.632252.

Genome annotation databases

EnsembliENST00000307641; ENSP00000303580; ENSG00000168256. [Q9NYR9-1]
ENST00000393880; ENSP00000377458; ENSG00000168256. [Q9NYR9-1]
ENST00000393881; ENSP00000377459; ENSG00000168256. [Q9NYR9-1]
ENST00000393885; ENSP00000377463; ENSG00000168256. [Q9NYR9-1]
ENST00000449471; ENSP00000401976; ENSG00000168256. [Q9NYR9-3]
ENST00000479407; ENSP00000465633; ENSG00000168256. [Q9NYR9-4]
GeneIDi28511.
KEGGihsa:28511.
UCSCiuc002hyq.3. human. [Q9NYR9-1]
uc010wge.2. human. [Q9NYR9-3]

Polymorphism and mutation databases

BioMutaiNKIRAS2.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF229840 mRNA. Translation: AAF34999.1.
AK027265 mRNA. Translation: BAB55006.1. Sequence problems.
AK054571 mRNA. Translation: BAG51392.1.
AK297975 mRNA. Translation: BAG60285.1.
DB126967 mRNA. No translation available.
AL137682 mRNA. Translation: CAB70873.2.
DQ314882 Genomic DNA. Translation: ABC40741.1.
AC105024 Genomic DNA. No translation available.
CH471152 Genomic DNA. Translation: EAW60791.1.
BC007450 mRNA. Translation: AAH07450.1.
BC063498 mRNA. Translation: AAH63498.1.
CCDSiCCDS11415.1. [Q9NYR9-1]
CCDS45679.1. [Q9NYR9-3]
CCDS45680.1. [Q9NYR9-4]
PIRiT46440.
RefSeqiNP_001001349.1. NM_001001349.2. [Q9NYR9-1]
NP_001138399.1. NM_001144927.1. [Q9NYR9-1]
NP_001138400.1. NM_001144928.1. [Q9NYR9-3]
NP_001138401.1. NM_001144929.1. [Q9NYR9-4]
NP_060065.2. NM_017595.5. [Q9NYR9-1]
XP_005257308.1. XM_005257251.1. [Q9NYR9-1]
UniGeneiHs.632252.

3D structure databases

ProteinModelPortaliQ9NYR9.
SMRiQ9NYR9. Positions 6-155.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118388. 6 interactions.
IntActiQ9NYR9. 3 interactions.
MINTiMINT-6945136.
STRINGi9606.ENSP00000303580.

PTM databases

PhosphoSiteiQ9NYR9.

Polymorphism and mutation databases

BioMutaiNKIRAS2.
DMDMi74734716.

Proteomic databases

MaxQBiQ9NYR9.
PaxDbiQ9NYR9.
PRIDEiQ9NYR9.

Protocols and materials databases

DNASUi28511.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000307641; ENSP00000303580; ENSG00000168256. [Q9NYR9-1]
ENST00000393880; ENSP00000377458; ENSG00000168256. [Q9NYR9-1]
ENST00000393881; ENSP00000377459; ENSG00000168256. [Q9NYR9-1]
ENST00000393885; ENSP00000377463; ENSG00000168256. [Q9NYR9-1]
ENST00000449471; ENSP00000401976; ENSG00000168256. [Q9NYR9-3]
ENST00000479407; ENSP00000465633; ENSG00000168256. [Q9NYR9-4]
GeneIDi28511.
KEGGihsa:28511.
UCSCiuc002hyq.3. human. [Q9NYR9-1]
uc010wge.2. human. [Q9NYR9-3]

Organism-specific databases

CTDi28511.
GeneCardsiGC17P040170.
HGNCiHGNC:17898. NKIRAS2.
MIMi604497. gene.
neXtProtiNX_Q9NYR9.
PharmGKBiPA134968907.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG302793.
GeneTreeiENSGT00390000006495.
HOGENOMiHOG000230991.
HOVERGENiHBG105089.
InParanoidiQ9NYR9.
KOiK17197.
PhylomeDBiQ9NYR9.
TreeFamiTF314483.

Miscellaneous databases

ChiTaRSiNKIRAS2. human.
GeneWikiiNKIRAS2.
GenomeRNAii28511.
NextBioi50970.
PROiQ9NYR9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NYR9.
CleanExiHS_NKIRAS2.
ExpressionAtlasiQ9NYR9. baseline and differential.
GenevestigatoriQ9NYR9.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERiPTHR24070. PTHR24070. 1 hit.
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51419. RAB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A subclass of Ras proteins that regulate the degradation of IkappaB."
    Fenwick C., Na S.-Y., Voll R.E., Zhong H., Im S.-Y., Lee J.W., Ghosh S.
    Science 287:869-873(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH NFKBIA AND NFKBIB.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
    Tissue: Embryo and Thymus.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Testis.
  4. NHLBI resequencing and genotyping service (RS&G)
    Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain and Muscle.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiKBRS2_HUMAN
AccessioniPrimary (citable) accession number: Q9NYR9
Secondary accession number(s): A6NCZ5
, B3KNN0, B4DNM3, Q6PK52, Q96KC7, Q9NSX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: October 1, 2000
Last modified: April 29, 2015
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.