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Protein

NF-kappa-B essential modulator

Gene

IKBKG

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

Functioni

Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri389 – 419CCHC NOA-typePROSITE-ProRule annotationAdd BLAST31

GO - Molecular functioni

  • K63-linked polyubiquitin binding Source: GO_Central
  • linear polyubiquitin binding Source: ParkinsonsUK-UCL
  • metal ion binding Source: UniProtKB-KW
  • protein domain specific binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • signal transducer activity Source: ProtInc
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • activation of MAPK activity Source: Reactome
  • apoptotic process Source: ProtInc
  • cellular response to DNA damage stimulus Source: UniProtKB
  • establishment of vesicle localization Source: UniProtKB
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • immune response Source: ProtInc
  • inflammatory response Source: UniProtKB
  • innate immune response Source: UniProtKB
  • JNK cascade Source: Reactome
  • negative regulation of neuron death Source: ParkinsonsUK-UCL
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
  • response to virus Source: UniProtKB
  • stimulatory C-type lectin receptor signaling pathway Source: Reactome
  • stress-activated MAPK cascade Source: Reactome
  • T cell receptor signaling pathway Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

DNA damage, Host-virus interaction, Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073009-MONOMER.
ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1236974. ER-Phagosome pathway.
R-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-450302. activated TAK1 mediates p38 MAPK activation.
R-HSA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5602636. IKBKB deficiency causes SCID.
R-HSA-5603027. IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
R-HSA-5603029. IkBA variant leads to EDA-ID.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-937039. IRAK1 recruits IKK complex.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
SABIO-RKQ9Y6K9.
SIGNORiQ9Y6K9.

Names & Taxonomyi

Protein namesi
Recommended name:
NF-kappa-B essential modulator
Short name:
NEMO
Alternative name(s):
FIP-3
IkB kinase-associated protein 1
Short name:
IKKAP1
Inhibitor of nuclear factor kappa-B kinase subunit gamma
Short name:
I-kappa-B kinase subunit gamma
Short name:
IKK-gamma
Short name:
IKKG
Short name:
IkB kinase subunit gamma
NF-kappa-B essential modifier
Gene namesi
Name:IKBKG
Synonyms:FIP3, NEMO
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:5961. IKBKG.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • Note: Sumoylated NEMO accumulates in the nucleus in response to genotoxic stress.

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • IkappaB kinase complex Source: UniProtKB
  • intracellular Source: LIFEdb
  • mitotic spindle Source: UniProtKB
  • nucleus Source: UniProtKB
  • spindle pole Source: UniProtKB
  • ubiquitin ligase complex Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Ectodermal dysplasia, anhidrotic, with immunodeficiency X-linked (EDAID)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases.
See also OMIM:300291
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026495153L → R in EDAID. 2 PublicationsCorresponds to variant rs137853328dbSNPEnsembl.1
Natural variantiVAR_011320175R → P in EDAID. 1 PublicationCorresponds to variant rs179363868dbSNPEnsembl.1
Natural variantiVAR_011321227L → P in EDAID. 1 PublicationCorresponds to variant rs179363869dbSNPEnsembl.1
Natural variantiVAR_011322288A → G in EDAID. 1 PublicationCorresponds to variant rs137853330dbSNPEnsembl.1
Natural variantiVAR_011323311D → N in EDAID; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. 4 PublicationsCorresponds to variant rs179363867dbSNPEnsembl.1
Natural variantiVAR_011324406D → V in EDAID. 1 PublicationCorresponds to variant rs137853327dbSNPEnsembl.1
Natural variantiVAR_011325417C → F in EDAID. 2 PublicationsCorresponds to variant rs137853326dbSNPEnsembl.1
Natural variantiVAR_011326417C → R in EDAID; loss of sumoylation. 6 PublicationsCorresponds to variant rs137853325dbSNPEnsembl.1
Ectodermal dysplasia, anhidrotic, with immunodeficiency, osteopetrosis and lymphedema (OLEDAID)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by the association of anhidrotic ectodermal dysplasia with severe immunodeficiency, osteopetrosis and lymphedema.
See also OMIM:300301
Immunodeficiency, NEMO-related, without anhidrotic ectodermal dysplasia (NEMOID)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionPatients manifest immunodeficiency not associated with other abnormalities, and resulting in increased susceptibility to infections. Patients suffer from multiple episodes of infectious diseases.
See also OMIM:300584
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026496417C → Y in NEMOID. 1 PublicationCorresponds to variant rs137853326dbSNPEnsembl.1
Immunodeficiency 33 (IMD33)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA X-linked recessive form of Mendelian susceptibility to mycobacterial disease, a rare condition characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections, with the exception of Salmonella which infects less than 50% of these individuals.
See also OMIM:300636
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031959315E → A in IMD33; greatly impairs tandem ubiquitin binding. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant rs137853331dbSNPEnsembl.1
Natural variantiVAR_031960319R → Q in IMD33; impairs tandem ubiquitin binding. 2 PublicationsCorresponds to variant rs137853332dbSNPEnsembl.1
Recurrent isolated invasive pneumococcal disease 2 (IPD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRecurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.
See also OMIM:300640
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031958173R → G in IPD2. 1 PublicationCorresponds to variant rs179363866dbSNPEnsembl.1
Incontinentia pigmenti (IP)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring.
See also OMIM:308300
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02649157E → K in IP; shows the same luciferase activity as the control. 2 PublicationsCorresponds to variant rs148695964dbSNPEnsembl.1
Natural variantiVAR_02649290Missing in IP; only 46.3% of the activation obtained with the wild-type protein. 1 Publication1
Natural variantiVAR_026494123R → W in IP; shows the same luciferase activity as the control. 1 PublicationCorresponds to variant rs179363895dbSNPEnsembl.1
Natural variantiVAR_072603170L → P in IP. 1 Publication1
Natural variantiVAR_031958173R → G in IPD2. 1 PublicationCorresponds to variant rs179363866dbSNPEnsembl.1
Natural variantiVAR_072604173R → Q in IP. 1 Publication1
Natural variantiVAR_072605183Q → H in IP. 1 Publication1
Natural variantiVAR_072606314A → P in IP. 1 Publication1
Natural variantiVAR_072607322L → P in IP. 1 Publication1
Natural variantiVAR_042666323A → P in IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant rs179363865dbSNPEnsembl.1
Natural variantiVAR_009182407M → V in IP; impairs binding to ubiquitin. 3 PublicationsCorresponds to variant rs137853322dbSNPEnsembl.1
Natural variantiVAR_072608413H → Y in IP. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi68S → A: Increases formation of homodimers. 1 Publication1
Mutagenesisi68S → E: Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity. 1 Publication1
Mutagenesisi85S → A: Decreases ubiquitination and abolishes nuclear export. 1 Publication1
Mutagenesisi115K → R: No change in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi224K → R: No change in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi277K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-309. 1 Publication1
Mutagenesisi285K → R: Important decrease in the ubiquitination level; when associated with R-399. 1 Publication1
Mutagenesisi296E → A: No effet on oligomerization,impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 1 Publication1
Mutagenesisi300V → D: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi301L → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi304Q → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi307I → N: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi308Y → A: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi309K → A: Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277. 1 Publication1
Mutagenesisi312F → A: Greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs TNF-induced NF-kappa-B activation. 2 Publications1
Mutagenesisi312F → W: MNo effet on oligomerization, preferentially binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked). 2 Publications1
Mutagenesisi312F → Y: Impairs tandem ubiquitin binding. 2 Publications1
Mutagenesisi313Q → A: Impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi315E → Q: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi317Q → A or W: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi323A → D: Greatly impairs tandem ubiquitin binding. 1 Publication1
Mutagenesisi329L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-336. 2 Publications1
Mutagenesisi329L → P: Abolishes binding to polyubiquitin. 2 Publications1
Mutagenesisi336L → A: Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-329. 1 Publication1
Mutagenesisi399K → R: Abolishes BCL10-mediated but not RIPK2-mediated ubiquitination. Important decrease in the ubiquitination level; when associated with R-285. No change in the ubiquitination level; when associated with R-115 or R-224. 2 Publications1
Mutagenesisi414V → S: Abolishes binding to polyubiquitin. 1 Publication1
Mutagenesisi415M → S: Impairs binding to polyubiquitin. 1 Publication1

Keywords - Diseasei

Disease mutation, Ectodermal dysplasia, Osteopetrosis

Organism-specific databases

DisGeNETi8517.
MalaCardsiIKBKG.
MIMi300291. phenotype.
300301. phenotype.
300584. phenotype.
300636. phenotype.
300640. phenotype.
308300. phenotype.
OpenTargetsiENSG00000269335.
Orphaneti69088. Anhidrotic ectodermal dysplasia - immunodeficiency - osteopetrosis - lymphedema.
98813. Hypohidrotic ectodermal dysplasia with immunodeficiency.
464. Incontinentia pigmenti.
319612. X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency.
PharmGKBiPA29777.

Chemistry databases

ChEMBLiCHEMBL4967.

Polymorphism and mutation databases

DMDMi6685695.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000967821 – 419NF-kappa-B essential modulatorAdd BLAST419

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei31Phosphoserine; by IKKB1 Publication1
Modified residuei43Phosphoserine; by IKKB1 Publication1
Disulfide bondi54Interchain1 Publication
Modified residuei68Phosphoserine1 Publication1
Modified residuei85Phosphoserine; by ATM1 Publication1
Cross-linki111Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki139Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki143Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki246Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki264Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate2 Publications
Cross-linki283Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki285Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)3 Publications
Cross-linki292Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki302Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross-linki309Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate4 Publications
Cross-linki321Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki325Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Disulfide bondi347Interchain1 Publication
Modified residuei376Phosphoserine; by IKKB1 Publication1
Modified residuei387PhosphoserineCombined sources1 Publication1
Cross-linki399Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Phosphorylation at Ser-68 attenuates aminoterminal homodimerization.1 Publication
Polyubiquitinated on Lys-285 through 'Lys-63'; the ubiquitination is mediated by NOD2 and RIPK2 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway. Polyubiquitinated on Lys-399 through 'Lys-63'; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway. Monoubiquitinated on Lys-277 and Lys-309; promotes nuclear export. Polyubiquitinated through 'Lys-27' by TRIM23; involved in antiviral innate and inflammatory responses. Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-264, Lys-277, Lys-285, Lys-292, Lys-302, Lys-309 and Lys-326; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation. Polyubiquitinated on Lys-309 and Lys-321 via 'Lys-27'-linked ubiquitin by Shigella flexneri E3 ubiquitin-protein ligase ipah9.8, leading to its degradation by the proteasome. Deubiquitinated by USP10 in a TANK-dependent and -independent manner, leading to the negative regulation of NF-kappaB signaling upon DNA damage (PubMed:25861989).7 Publications
Sumoylated on Lys-277 and Lys-309 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues.5 Publications
Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity.1 Publication

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Y6K9.
PaxDbiQ9Y6K9.
PeptideAtlasiQ9Y6K9.
PRIDEiQ9Y6K9.

PTM databases

iPTMnetiQ9Y6K9.
PhosphoSitePlusiQ9Y6K9.

Expressioni

Tissue specificityi

Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Gene expression databases

BgeeiENSG00000073009.
CleanExiHS_IKBKG.
ExpressionAtlasiQ9Y6K9. baseline and differential.
GenevisibleiQ9Y6K9. HS.

Organism-specific databases

HPAiCAB010373.
HPA000426.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Interacts with COPS3, CYLD, NALP2, TRPC4AP and LRDD. Interacts with ATM; the complex is exported from the nucleus. Interacts with TRAF6. Interacts with HTLV-1 Tax oncoprotein; the interaction activates IKBKG. Interacts with IKBKE. Interacts with TANK; the interaction is enhanced by IKBKE and TBK1. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with ZFAND5. Interacts with RIPK2. Interacts with TNIP1 and TNFAIP3; TNIP1 facilitates the TNFAIP3-mediated de-ubiquitination of IKBKG. Interacts with TNFAIP3; the interaction is induced by TNF stimulation and by polyubiquitin. Binds polyubiquitin; the interaction is mediated by two domains; reports about the binding to 'Lys-63'-linked and/or linear polyubiquitin, respective binding affinities and stoichiometry are conflicting. Interacts with Shigella flexneri ipah9.8; the interaction promotes TNIP1-dependent 'Lys-27'-linked polyubiquitination of IKBKG which perturbs NF-kappa-B activation during bacterial infection. Interacts with NLRP10. Interacts with TANK; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with USP10; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with ZC3H12A; this interaction increases in response to DNA damage (PubMed:25861989).22 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ADAP2Q9NPF82EBI-81279,EBI-718895
ANXA1P040836EBI-81279,EBI-354007
ARL6IP4Q66PJ32EBI-81279,EBI-2683099
ATMQ133154EBI-81279,EBI-495465
ATRQ135352EBI-81279,EBI-968983
BCL10O959994EBI-81279,EBI-958922
CALB1P059373EBI-81279,EBI-4286943
CDC37Q165436EBI-81279,EBI-295634
CDK2P249414EBI-81279,EBI-375096
CHUKO1511121EBI-81279,EBI-81249
COPS3Q9UNS22EBI-81279,EBI-350590
FLT3P368882EBI-81279,EBI-3946257
GIT2Q141616EBI-81279,EBI-1046878
HSP90AA1P079003EBI-81279,EBI-296047
HSP90AB1P082383EBI-81279,EBI-352572
IKBKBO1492028EBI-81279,EBI-81266
ipaH9.8Q8VSC38EBI-81279,EBI-6125799From a different organism.
KRT18P057833EBI-81279,EBI-297888
KRT8P057872EBI-81279,EBI-297852
MALT1Q9UDY84EBI-81279,EBI-1047372
MYCP011063EBI-81279,EBI-447544
NFKBIAP259636EBI-81279,EBI-307386
PPP2CAP677754EBI-81279,EBI-712311
RBCK1Q9BYM84EBI-81279,EBI-2340624
RIPK1Q135467EBI-81279,EBI-358507
RNF7Q9UBF63EBI-81279,EBI-398632
RUSC1Q9BVN2-24EBI-81279,EBI-6257338
SENP2Q9HC623EBI-81279,EBI-714881
SHARPINQ9H0F64EBI-81279,EBI-3942966
SQSTM1Q135012EBI-81279,EBI-307104
SRCP129313EBI-81279,EBI-621482
SUMO1P631653EBI-81279,EBI-80140
SYT1P215793EBI-81279,EBI-524909
TBK1Q9UHD22EBI-81279,EBI-356402
TNFP013752EBI-81279,EBI-359977
TNFAIP3P215804EBI-81279,EBI-527670
TNIP1Q150254EBI-81279,EBI-357849
TNIP2Q8NFZ56EBI-81279,EBI-359372
UBCP0CG484EBI-81279,EBI-3390054
ZC3H12AQ5D1E82EBI-81279,EBI-747793

GO - Molecular functioni

  • K63-linked polyubiquitin binding Source: GO_Central
  • linear polyubiquitin binding Source: ParkinsonsUK-UCL
  • protein domain specific binding Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi114089. 316 interactors.
DIPiDIP-27528N.
IntActiQ9Y6K9. 193 interactors.
MINTiMINT-128245.
STRINGi9606.ENSP00000358622.

Chemistry databases

BindingDBiQ9Y6K9.

Structurei

Secondary structure

1419
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi50 – 108Combined sources59
Turni194 – 196Combined sources3
Helixi197 – 249Combined sources53
Helixi260 – 268Combined sources9
Helixi271 – 295Combined sources25
Helixi297 – 341Combined sources45
Beta strandi394 – 396Combined sources3
Turni398 – 400Combined sources3
Beta strandi403 – 406Combined sources4
Helixi407 – 416Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JVXNMR-A394-419[»]
2JVYNMR-A394-419[»]
3BRTX-ray2.25B/D44-111[»]
3BRVX-ray2.20B/D44-111[»]
3CL3X-ray3.20D/E150-272[»]
3FX0X-ray3.20A/B246-337[»]
4BWNX-ray2.27A/B258-344[»]
5AAYNMR-A392-419[»]
ProteinModelPortaliQ9Y6K9.
SMRiQ9Y6K9.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y6K9.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni44 – 111Interaction with CHUK/IKBKBAdd BLAST68
Regioni150 – 257Interaction with TANKAdd BLAST108
Regioni242 – 350Ubiquitin-binding (UBD)Add BLAST109
Regioni246 – 365Self-associationAdd BLAST120
Regioni251 – 419Required for interaction with TNFAIP3Add BLAST169
Regioni322 – 343Leucine-zipperSequence analysisAdd BLAST22
Regioni382 – 419Interaction with CYLD1 PublicationAdd BLAST38

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili49 – 356Sequence analysisAdd BLAST308

Domaini

The leucine-zipper domain and the CCHC NOA-type zinc-finger are essential for polyubiquitin binding and for the activation of IRF3.2 Publications

Sequence similaritiesi

Contains 1 CCHC NOA-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri389 – 419CCHC NOA-typePROSITE-ProRule annotationAdd BLAST31

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IJBJ. Eukaryota.
ENOG410Y1FG. LUCA.
GeneTreeiENSGT00530000063808.
HOGENOMiHOG000293233.
HOVERGENiHBG000417.
InParanoidiQ9Y6K9.
KOiK07210.
OMAiEFLMQKF.
OrthoDBiEOG091G0576.
PhylomeDBiQ9Y6K9.
TreeFamiTF326608.

Family and domain databases

InterProiIPR032419. CC2-LZ_dom.
IPR021063. NEMO_N.
[Graphical view]
PfamiPF16516. CC2-LZ. 1 hit.
PF11577. NEMO. 1 hit.
[Graphical view]
PROSITEiPS51801. ZF_CCHC_NOA. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y6K9-1) [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
MNRHLWKSQL CEMVQPSGGP AADQDVLGEE SPLGKPAMLH LPSEQGAPET
60 70 80 90 100
LQRCLEENQE LRDAIRQSNQ ILRERCEELL HFQASQREEK EFLMCKFQEA
110 120 130 140 150
RKLVERLGLE KLDLKRQKEQ ALREVEHLKR CQQQMAEDKA SVKAQVTSLL
160 170 180 190 200
GELQESQSRL EAATKECQAL EGRARAASEQ ARQLESEREA LQQQHSVQVD
210 220 230 240 250
QLRMQGQSVE AALRMERQAA SEEKRKLAQL QVAYHQLFQE YDNHIKSSVV
260 270 280 290 300
GSERKRGMQL EDLKQQLQQA EEALVAKQEV IDKLKEEAEQ HKIVMETVPV
310 320 330 340 350
LKAQADIYKA DFQAERQARE KLAEKKELLQ EQLEQLQREY SKLKASCQES
360 370 380 390 400
ARIEDMRKRH VEVSQAPLPP APAYLSSPLA LPSQRRSPPE EPPDFCCPKC
410
QYQAPDMDTL QIHVMECIE
Length:419
Mass (Da):48,198
Last modified:May 30, 2000 - v2
Checksum:i322D1037881447FF
GO
Isoform 2 (identifier: Q9Y6K9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MALVIQVGKLRPREVRTPQTINPSLFPSLPVKLSSIIEVPSGGERCCSRRTLVYKARAFWKGAPLPCWM

Show »
Length:487
Mass (Da):55,787
Checksum:i7A39E991E0013A73
GO
Isoform 3 (identifier: Q9Y6K9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     174-224: Missing.
     257-304: Missing.

Show »
Length:320
Mass (Da):36,953
Checksum:i3BEF2487C4446725
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti341S → R in AAD12183 (PubMed:9927690).Curated1
Sequence conflicti387S → R in AAD12183 (PubMed:9927690).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02649157E → K in IP; shows the same luciferase activity as the control. 2 PublicationsCorresponds to variant rs148695964dbSNPEnsembl.1
Natural variantiVAR_02649290Missing in IP; only 46.3% of the activation obtained with the wild-type protein. 1 Publication1
Natural variantiVAR_026493113D → N.1 PublicationCorresponds to variant rs179363896dbSNPEnsembl.1
Natural variantiVAR_026494123R → W in IP; shows the same luciferase activity as the control. 1 PublicationCorresponds to variant rs179363895dbSNPEnsembl.1
Natural variantiVAR_026495153L → R in EDAID. 2 PublicationsCorresponds to variant rs137853328dbSNPEnsembl.1
Natural variantiVAR_072603170L → P in IP. 1 Publication1
Natural variantiVAR_031958173R → G in IPD2. 1 PublicationCorresponds to variant rs179363866dbSNPEnsembl.1
Natural variantiVAR_072604173R → Q in IP. 1 Publication1
Natural variantiVAR_011320175R → P in EDAID. 1 PublicationCorresponds to variant rs179363868dbSNPEnsembl.1
Natural variantiVAR_072605183Q → H in IP. 1 Publication1
Natural variantiVAR_011321227L → P in EDAID. 1 PublicationCorresponds to variant rs179363869dbSNPEnsembl.1
Natural variantiVAR_011322288A → G in EDAID. 1 PublicationCorresponds to variant rs137853330dbSNPEnsembl.1
Natural variantiVAR_011323311D → N in EDAID; abolishes binding to polyubiquitin ('K63'-linked and linear) and greatly impairs tandem ubiquitin binding. 4 PublicationsCorresponds to variant rs179363867dbSNPEnsembl.1
Natural variantiVAR_072606314A → P in IP. 1 Publication1
Natural variantiVAR_031959315E → A in IMD33; greatly impairs tandem ubiquitin binding. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant rs137853331dbSNPEnsembl.1
Natural variantiVAR_031960319R → Q in IMD33; impairs tandem ubiquitin binding. 2 PublicationsCorresponds to variant rs137853332dbSNPEnsembl.1
Natural variantiVAR_072607322L → P in IP. 1 Publication1
Natural variantiVAR_042666323A → P in IP; diminishes interaction with TRAF6 and polyubiquitination, greatly impairs tandem ubiquitin binding. Impairs oligomerization, greatly impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. 3 PublicationsCorresponds to variant rs179363865dbSNPEnsembl.1
Natural variantiVAR_011324406D → V in EDAID. 1 PublicationCorresponds to variant rs137853327dbSNPEnsembl.1
Natural variantiVAR_009182407M → V in IP; impairs binding to ubiquitin. 3 PublicationsCorresponds to variant rs137853322dbSNPEnsembl.1
Natural variantiVAR_072608413H → Y in IP. 1 Publication1
Natural variantiVAR_011325417C → F in EDAID. 2 PublicationsCorresponds to variant rs137853326dbSNPEnsembl.1
Natural variantiVAR_011326417C → R in EDAID; loss of sumoylation. 6 PublicationsCorresponds to variant rs137853325dbSNPEnsembl.1
Natural variantiVAR_026496417C → Y in NEMOID. 1 PublicationCorresponds to variant rs137853326dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0410001M → MALVIQVGKLRPREVRTPQT INPSLFPSLPVKLSSIIEVP SGGERCCSRRTLVYKARAFW KGAPLPCWM in isoform 2. 1 Publication1
Alternative sequenceiVSP_041001174 – 224Missing in isoform 3. 1 PublicationAdd BLAST51
Alternative sequenceiVSP_041002257 – 304Missing in isoform 3. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF062089 mRNA. Translation: AAD12183.1.
AF091453 mRNA. Translation: AAD38081.1.
AF074382 mRNA. Translation: AAC36330.1.
AJ271718 Genomic DNA. Translation: CAB93146.1.
AF261086 mRNA. Translation: AAF99679.1.
AY114157 mRNA. Translation: AAM44073.1.
AK000593 mRNA. No translation available.
BT019621 mRNA. Translation: AAV38427.1.
AF277315 Genomic DNA. Translation: AAL27012.1.
BC000299 mRNA. Translation: AAH00299.1.
BC012114 mRNA. Translation: AAH12114.1.
BC046922 mRNA. Translation: AAH46922.1.
BC050612 mRNA. Translation: AAH50612.1.
CCDSiCCDS14757.1. [Q9Y6K9-1]
CCDS48196.1. [Q9Y6K9-2]
CCDS48197.1. [Q9Y6K9-3]
RefSeqiNP_001093326.2. NM_001099856.4. [Q9Y6K9-2]
NP_001093327.1. NM_001099857.2. [Q9Y6K9-1]
NP_001138727.1. NM_001145255.2. [Q9Y6K9-3]
NP_001308325.1. NM_001321396.1. [Q9Y6K9-1]
NP_001308326.1. NM_001321397.1.
NP_003630.1. NM_003639.4. [Q9Y6K9-1]
UniGeneiHs.43505.

Genome annotation databases

EnsembliENST00000594239; ENSP00000471166; ENSG00000269335. [Q9Y6K9-1]
ENST00000611071; ENSP00000479662; ENSG00000269335. [Q9Y6K9-1]
ENST00000611176; ENSP00000478616; ENSG00000269335. [Q9Y6K9-3]
ENST00000618670; ENSP00000483825; ENSG00000269335. [Q9Y6K9-2]
GeneIDi8517.
KEGGihsa:8517.
UCSCiuc033fbu.1. human. [Q9Y6K9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

IKBKGbase

IKBKG mutation db

Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF062089 mRNA. Translation: AAD12183.1.
AF091453 mRNA. Translation: AAD38081.1.
AF074382 mRNA. Translation: AAC36330.1.
AJ271718 Genomic DNA. Translation: CAB93146.1.
AF261086 mRNA. Translation: AAF99679.1.
AY114157 mRNA. Translation: AAM44073.1.
AK000593 mRNA. No translation available.
BT019621 mRNA. Translation: AAV38427.1.
AF277315 Genomic DNA. Translation: AAL27012.1.
BC000299 mRNA. Translation: AAH00299.1.
BC012114 mRNA. Translation: AAH12114.1.
BC046922 mRNA. Translation: AAH46922.1.
BC050612 mRNA. Translation: AAH50612.1.
CCDSiCCDS14757.1. [Q9Y6K9-1]
CCDS48196.1. [Q9Y6K9-2]
CCDS48197.1. [Q9Y6K9-3]
RefSeqiNP_001093326.2. NM_001099856.4. [Q9Y6K9-2]
NP_001093327.1. NM_001099857.2. [Q9Y6K9-1]
NP_001138727.1. NM_001145255.2. [Q9Y6K9-3]
NP_001308325.1. NM_001321396.1. [Q9Y6K9-1]
NP_001308326.1. NM_001321397.1.
NP_003630.1. NM_003639.4. [Q9Y6K9-1]
UniGeneiHs.43505.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JVXNMR-A394-419[»]
2JVYNMR-A394-419[»]
3BRTX-ray2.25B/D44-111[»]
3BRVX-ray2.20B/D44-111[»]
3CL3X-ray3.20D/E150-272[»]
3FX0X-ray3.20A/B246-337[»]
4BWNX-ray2.27A/B258-344[»]
5AAYNMR-A392-419[»]
ProteinModelPortaliQ9Y6K9.
SMRiQ9Y6K9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114089. 316 interactors.
DIPiDIP-27528N.
IntActiQ9Y6K9. 193 interactors.
MINTiMINT-128245.
STRINGi9606.ENSP00000358622.

Chemistry databases

BindingDBiQ9Y6K9.
ChEMBLiCHEMBL4967.

PTM databases

iPTMnetiQ9Y6K9.
PhosphoSitePlusiQ9Y6K9.

Polymorphism and mutation databases

DMDMi6685695.

Proteomic databases

EPDiQ9Y6K9.
PaxDbiQ9Y6K9.
PeptideAtlasiQ9Y6K9.
PRIDEiQ9Y6K9.

Protocols and materials databases

DNASUi8517.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000594239; ENSP00000471166; ENSG00000269335. [Q9Y6K9-1]
ENST00000611071; ENSP00000479662; ENSG00000269335. [Q9Y6K9-1]
ENST00000611176; ENSP00000478616; ENSG00000269335. [Q9Y6K9-3]
ENST00000618670; ENSP00000483825; ENSG00000269335. [Q9Y6K9-2]
GeneIDi8517.
KEGGihsa:8517.
UCSCiuc033fbu.1. human. [Q9Y6K9-1]

Organism-specific databases

CTDi8517.
DisGeNETi8517.
GeneCardsiIKBKG.
GeneReviewsiIKBKG.
H-InvDBHIX0203333.
HGNCiHGNC:5961. IKBKG.
HPAiCAB010373.
HPA000426.
MalaCardsiIKBKG.
MIMi300248. gene.
300291. phenotype.
300301. phenotype.
300584. phenotype.
300636. phenotype.
300640. phenotype.
308300. phenotype.
neXtProtiNX_Q9Y6K9.
OpenTargetsiENSG00000269335.
Orphaneti69088. Anhidrotic ectodermal dysplasia - immunodeficiency - osteopetrosis - lymphedema.
98813. Hypohidrotic ectodermal dysplasia with immunodeficiency.
464. Incontinentia pigmenti.
319612. X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency.
PharmGKBiPA29777.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJBJ. Eukaryota.
ENOG410Y1FG. LUCA.
GeneTreeiENSGT00530000063808.
HOGENOMiHOG000293233.
HOVERGENiHBG000417.
InParanoidiQ9Y6K9.
KOiK07210.
OMAiEFLMQKF.
OrthoDBiEOG091G0576.
PhylomeDBiQ9Y6K9.
TreeFamiTF326608.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000073009-MONOMER.
ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1236974. ER-Phagosome pathway.
R-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-202424. Downstream TCR signaling.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-450302. activated TAK1 mediates p38 MAPK activation.
R-HSA-450321. JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5602636. IKBKB deficiency causes SCID.
R-HSA-5603027. IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
R-HSA-5603029. IkBA variant leads to EDA-ID.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-937039. IRAK1 recruits IKK complex.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
SABIO-RKQ9Y6K9.
SIGNORiQ9Y6K9.

Miscellaneous databases

ChiTaRSiIKBKG. human.
EvolutionaryTraceiQ9Y6K9.
GeneWikiiIKBKG.
GenomeRNAii8517.
PROiQ9Y6K9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000073009.
CleanExiHS_IKBKG.
ExpressionAtlasiQ9Y6K9. baseline and differential.
GenevisibleiQ9Y6K9. HS.

Family and domain databases

InterProiIPR032419. CC2-LZ_dom.
IPR021063. NEMO_N.
[Graphical view]
PfamiPF16516. CC2-LZ. 1 hit.
PF11577. NEMO. 1 hit.
[Graphical view]
PROSITEiPS51801. ZF_CCHC_NOA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNEMO_HUMAN
AccessioniPrimary (citable) accession number: Q9Y6K9
Secondary accession number(s): Q7LBY6, Q7Z7F1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: November 30, 2016
This is version 187 of the entry and version 2 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.